Syllabus for GPAT-2010 Examination

Syllabus for GPAT-2010 Examination

Natural Products :
Pharmacognosy & Phytochemistry - Chemistry, tests, isolation, characterization and estimation of phytopharmaceuticals belonging to the group of Alkaloids, Glycosides, Terpenoids, Ster oids, Bioflavanoids, Purines, Guggul lipids. Pharmacognosy of crude drugs that contain the above constituents. Standardization of raw materials and herbal products. WHO guidelines. Quantitative microscopy including modern techniques used for evaluation. Biotechnological principles and techniques for plant development, Tissue culture.
Pharmacology :
General pharmacological principles including Toxicology. Drug interaction. Pharmacology of drugs acting on Central nervous system, Cardiovascular system, Autonomic nervous system, Gastro intestinal system and Respiratory system. Pharmacology of Autocoids, Hormones, Hormone antagonists, chemotherapeutic agents including anticancer drugs. Bioassays, Immuno Pharmacology. Drugs acting on the blood & blood forming organs. Drugs acting on the renal system.
Medicinal Chemistry :
Structure, nomenclature, classification, synthesis, SAR and metabolism of the following category of drugs, which are official in Indian Pharmacopoeia and British Pharmacopoeia. Introduction to drug design. Stereochemistry of drug molecules. Hypnotics and Sedatives, Analgesics, NSAIDS, Neuroleptics, Antidepressants, Anxiolytics, Anticonvulsants, Antihistaminics, Local Anaesthetics, Cardio Vascular drugs - Antianginal agents Vasodilators, Adrenergic & Cholinergic drugs, Cardiotonic agents, Diuretics, Anti-hypertensive drugs, Hypoglycemic agents, Antilipedmic agents, Coagulants, Anticoagulants, Antiplatelet agents. Chemotherapeutic agents - Antibiotics, Antibacterials, Sulphadrugs. Antiprotozoal drugs, Antiviral, Antitubercular, Antimalarial, Anticancer, Antiamoebic drugs. Diagnostic agents. Preparation and storage and uses of official Radiopharmaceuticals, Vitamins and Hormones. Eicosanoids and their application.
Pharmaceutics :
Development, manufacturing standards Q.C. limits, labeling, as per the pharmacopoeial requirements. Storage of different dosage forms and new drug delivery systems. Biopharmaceutics and Pharmacokinetics and their importance in formulation. Formulation and preparation of cosmetics - lipstick, shampoo, creams, nail preparations and dentifrices. Pharmaceutical calculations.
Pharmaceutical Jurisprudence :
Drugs and cosmetics Act and rules with respect to manufacture, sales and storage. Pharmacy Act. Pharmaceutical ethics.
Pharmaceutical Analysis :
Principles, instrumentation and applications of the following: Absorption spectroscopy (UV, visible & IR). Fluorimetry, Flame photometry, Potentiometry. Conductometry and Polarography. Pharmacopoeial assays. Principles of NMR, ESR, Mass spectroscopy. X-ray diffraction analysis and different chromatographic methods.
Biochemistry :
Biochemical role of hormones, Vitamins, Enzymes, Nucleic acids, Bioenergetics. General principles of immunology. Immunological. Metabolism of carbohydrate, lipids, proteins. Methods to determine, kidney & liver function. Lipid profiles.
Microbiology :
Principles and methods of microbiological assays of the Pharmacopoeia. Methods of preparation of official sera and vaccines. Serological and diagnostics tests. Applications of microorganisms in Bio Conversions and in Pharmaceutical industry.


Clinical Pharmacy :
Therapeutic Drug Monitoring Dosage regimen in Pregnancy and Lactation, Pediatrics and Geriatrics. Renal and hepatic impairment. Drug - Drug interactions and Drug - food interactions, Adverse Drug reactions. Medication History, interview and Patient counseling.

People’s Institute of Pharmacy & Research Centre

People’s Institute of Pharmacy & Research Centre
Bhanpur, By-Pass road,
Bhopal-462037 (M.P.)

The aim of the People’s Institute of Pharmacy & Research Centre is committed to quality of education. Demand for well-qualified Pharmacy manpower is increasing day by day with the proliferation of many new companies and a greater demand for competent candidates in the Pharmaceutical sector is generated. Job opportunities for Pharmacy professionals have increased in India and abroad. Keeping this in view, the members of SJPN (Charitable Trust) have proposed to start People’s Institute of Pharmacy & Research Centre (PIP&RC) at Bhanpur, Bhopal, approx. 5.5 km from the Railway Station as well as Airport.

ABHINAMDAN

Amrit Singh

Complexometric

These titrations are based on complexation reactions.
Most often used reagent is EDTA - EthyleneDiamineTetraAcetic acid. There are also other similar chelating agents (EGTA, CDTA and so on) used. In some of other methods Ag+ is used as a titrant for determining cyanides and Hg2+ as a titrant in Cl- determination.
Changing property of the solution is usually the concentration of the complexed substance, although in some cases it can be much more convenient to express results in terms of titrant concentration. As its concentration changes by many orders of magnitude, and is almost always smaller than 1, we use negative logarithmic scale, similar to that used in pH definition.
In the case of determination of metals detection of the endpoint is mainly based on substances that change color when creating complexes with determined metals. One of these indicators is eriochrome black T, substance that in pH between 7 and 11 is blue when free, and black when forms a complex with metal, other examples are pyrocatechin violet and murexide. It is important that formation constant for these complexes is low enough, so that titrant reacts with complexed ions first.

Iodometry

Iodometry

Iodometry is one of the most important redox titration methods. Iodine reacts directly, fast and quantitively with many organic and inorganic substances. Thanks to its relatively low, pH independent redox potential, and reversibility of the iodine/iodide reaction, iodometry can be used both to determine amount of reducing agents (by direct titration with iodine) and of oxidizing agents (by titration of iodine with thiosulfate). In all cases the same simple and reliable method of end point detection, based on blue starch complex, can be used.
Reversible iodine/iodide reaction mentioned above is
2I- ↔ I2 + 2e-
and obviously whether it should be treated as oxidation with iodine or reduction with iodides depends on the other redox system involved.
Second important reaction used excesivelly in iodometry is reduction of iodine with thiosulfate:
2S2O32- + I2 → S4O62- + 2I-
In the case of both reactions it is better to avoid low pH. Thiosulfate is unstable in the presence of acids, and iodides in low pH can be oxidized by air oxygen to iodine. Both processes can be source of titration errors.
Iodine is very weakly soluble in the water, and can be easily lost from the solution due to its volatility. However, in the presence of excess iodides iodine creates I3- ions. This lowers free iodine concentration and such solutions are stable enough to be used in lab practice. Still, we should remember that their shelf life is relatively short (they should be kept tightly closed in dark brown bottles, and standardized every few weeks). Iodine solutions are prepared dissolving elemental iodine directly in the iodides solution. Elemental iodine can be prepared very pure through sublimation, but because of its high volatility it is difficult to weight. Thus use of iodine as a standard substance, although possible, is not easy nor recommended. Iodine solutions can be easily normalized against arsenic (III) oxide (As2O3) or sodium thiosulfate solution.
It is also possible to prepare iodine solutions mixing potassium iodide with potassium iodate in the presence of strong acid:
5I- + IO3- + 6H+ → 3I2 + 3H2O
Potassium iodate is a primary substance, so solution prepared this way can have exactly known concentration. However, this approach is not cost effective and in lab practice it is much better to use iodate as a primary substance to standardize thiosulfate, and then standardize iodine solution against thiosulfate.

end point detection with starch

Iodine in water solutions is usually colored strong enough so that its presence can be detected visually. However, close to the end point, when the iodine concentration is very low, its yellowish color is very pale and can be easily overlooked. Thus for the end point detection starch solutions are used.
Iodine gets adsorbed on the starch molecule surface and product of adsortion has strong, blue color. Exact mechanism behind adsorption and color change is not known, see for example this explanation of starch as an indicator usage.
In the presence of small amounts of iodine adsorption and desorption are fast and reversible. However, when the concentration of iodine is high, it gets bonded with starch relatively strong, and desorption becomes slow, which makes detection of the end point relatively difficult. Luckily high concentrations of iodine are easily visible, so if we are using thiosulfate to titrate solution that initially contains high iodine concentration, we can titrate till the solution gets pale and add starch close to the end point. In the case of titration with iodine solution we can add starch at the very beginning, as high iodine concentrations are not possible before we are long past the end point.
At the elevated temperatures adsorption of the iodine on the starch surface decreases, so titrations should be done in the cold.
Finally, it is worth of noting that starch solutions, containing natural carbohydrate, have to be either prepared fresh, or conserved with antibacterial agent like mercuric iodide HgI2.

Solutions used in iodometric titrations

Two most important solutions used in iodometric titrations are solution of iodine and solution of sodium thiosulfate. Both substances can be easily obtained in a pure form, but their other characteristics (volatility, hard to control amount of water of crystallization) make them difficult to use as a primary standards.
It is also worth of mentioning that both solutions are not quite stable and they can not be stored for a prolonged period of time. Iodine can be lost from the solution due to its volatility, while thiosulfate slowly decomposes giving off elemental sulfur. The latter process is easily visible, as thiosulfate solutions become slightly cloudy with time.
Iodine solution
It is not difficult to prepare high purity iodine through sublimation, but - due to its volatility - iodine is difficult to weight accurately, as it tends to run away. To minimize losses it should be weight in closed weighing bottle. Iodine should be kept in a closed bottles also because it is highly corrosive and it vapor can damage delicate mechanism of analytical balance.
Commonly used solutions are 0.05M (0.1 normal).
To find out amounts of substances required to prepare the solution for a needed volume use ChemBuddy concentration calculator. Download the iodine solution preparation file. Open it with the free trial version of the concentration calculator. After opening the file enter solution volume and click on the Show recipe button. Read amounts of the substances, but don't follow the general directions. It is better to use as small initial volume of the solution as possible, that is, dissolve potassium iodide in about 1/100th of the final volume of water, before adding iodine.
To minimalize losses it is important to transfer iodine to the solution as fast as possible, or even to weight a 1% excess. Solution should be kept in dark glass bottle with grinded glass stopper and standardized every few weeks or before use.
Sodium thiosulfate solution
Sodium thiosulafte can be realtively easily obtained in a pure form, but it is quite difficult to obtain samples with known amount of water of crystallization, as the exact composition of the solid is very temperature and humidity dependent. Thus solution has to be standardized against potassium iodate KIO3 or potassium dichromate.
Commonly used solutions are 0.1M (0.1 normal).
To prepare the recipe for a needed volume of the solution use ChemBuddy concentration calculator. Download the sodium thiosulfate solution preparation file. Open it with the free trial version of the concentration calculator. After opening the file enter solution volume and click on the Show recipe button.
Small amount of carbonate added helps keep solution pH above 7, which slows down thiosulfate decomposition. Some sources also call for addition of 0.5 mL chloform per liter of the solution, to stop possible growth of bacteria that can speed up decomposition process.
Starch solution
Starch solution is used for end point detection in iodometric titration.
To prepare starch indicator solution, add 1 gram of starch (either corn or potato) into 10 mL of distilled water, shake well, and pour into 100 mL of boiling, distilled water. Stir thoroughly and boil for a 1 minute. Leave to cool down. If the precipitate forms, decant the supernatant and use as the indicator solution. To make solution long lasting add a pinch of mercury iodide or salicylic acid, otherwise it can spoil after a few days.
2% sodium bicarbonate
This solution is used for neutralization of sodium arsenite, before it is titrated with iodine solution during iodine solution standardization.

0.05M iodine standardization against arsenic trioxide
Chemical characteristics of the arsenic trioxide As2O3 make it a good candidate for a standard substance in many potentiometric methods, however, because of its toxicity it is used less and less frequently.
Arsenic oxide is dissolved in sodium hydroxide, producing sodium arsenite, which is a good reducing agent. In iodometry it is quantitatively oxidized by iodine to arsenate:
Na3AsO3 + I2 + H2O → Na3AsO4 + 2I- + 2H+
Direction of this reaction depends on pH - in acidic solutions As(V) is able to oxidize iodides to iodine. To guarantee correct pH of the solution we will add solution of sodium bicarbonate NaHCO3.
Interestingly, when using As2O3 as a standard substance in other types of redox titrations, we often add small amount of iodide or iodate to speed up the reaction. For obvious reasons in the case of iodometric titration we don't have to.
Procedure to follow:
Weight exactly about 0.15-0.20g of dry arsenic trioxide and transfer it to Erlenmayer flask.
Add 10 mL of 1M sodium hydroxide solution and dissolve solid.
Add a drop of phenolphthalein solution.
Neutralize with 0.5M sulfuric acid, adding several drops of excess acid after solution loses its color.
Add slowly (to not cause the solution to foam up) 50 mL of 2% NaHCO3 solution.
Add 5 mL of the starch solution.
Titrate swirling the flask, until a blue color persists for 20 seconds.
To calculate iodine solution concentration use EBAS - stoichiometry calculator. Download iodine standardization against arsenic trioxide reaction file, open it with the free trial version of the stoichiometry calculator.
Note, that to be consistent with the use of arsenic trioxide and its molar mass, reaction equation is not the one shown above, but
As2O3 + 2I2 + 5H2O → 2AsO43- + 4I- + 10H+
These are equivalent. Enter arsenic troxide mass in the upper (input) frame in the mass edit field above As2O3 formula. Click n=CV button below iodine in the output frame, enter volume of the solution used, read solution concentration

Potentiometric titrations

Potentiometric titrations

These titrations are based on redox reactions.
There are many redox reagents used in redox titrations. To list a few - potassium permanganate is used for determination of Fe2+, H2O2 and oxalic acid. Potassium dichromate for determination of Fe2+ and Cu in CuCl. Bromate is used for tin and phenol, iodides (titrated with sodium thiosulfate) for H2O2 and Cu2+. Cerium (IV) can be used to determine ferrocyanides and nitrites. There are also many other methods.
Changing property of the solution is its redox potential.
Commonly used indicators are substances that can exist in two forms - oxidized and reduced - that differ in color. Potential at which the substance changes color must be such that the change occurs close to the equivalence point. Examples of such substances are ferroin, diphenylamine or nile blue. Sometimes indicators that are oxidized irreversibly are used. However, in most popular redox titrations there is no need for a special indicator - permanganate has strong color by itself, iodine gives strong color when combined with starch, so their presence or disappearance can be easily detected without additional indicators.

End point detection

Many things that have been told about use of indicators in acid-base titration hold also for potentiometric titrations. The higher the concentration of the titrated substance and the titrant, the longer the steep part of the titration curve and the easier the redox indicator selection. In the case of one color indicators, potential at which indicator color starts to be visible depends on the indicator concentration. Depending on the situation we should either titrate to the full change of color or to the first visible change of color - and so on.
However, there are also important differences. The most obvious one is - while the general idea that observed color depends on the ratio of concentrations of both reduced and oxidized forms still holds, ratio of concentrations is not pH dependent, but redox potential dependent. We can easily calculate ratio of the concentrations of both forms using Nernst equation:

Let's assume - as we did in the case of pH indicators - that for the complete color change we have to move from 10:1 to 1:10 concentration ratio. That means we have to move from the potential

at 25 °C (more precisely it should be 118.2 mV, but as we started with an approximate rule 10:1 to 1:10, such accuracy is not necessary). This is a useful rule of thumb - 120 mV will be enough always. For many indicators reaction requires 2 electrons, so 60 mV change is enough for the observable color change.
Table below contains some of the popular redox indicators. Note, that reduced forms of many indicators are colorless - that means, that indicator concentration plays important role. Also note, that many of these substances are weak acids/bases, thus formal potentials of their reactions can depend on the solution pH. Some of these substances are even used as pH indicators, so their color depends both on the pH and redox potential of the system, which makes selecting them even more complicated.

Interestingly, in the case of three popular potentiometric titrations we usually don't use redox indicators, but specific indicators, that work only in the case of these methods.
In the case of permanganometry there is no need for indicator - small excess of permanganate is immediately visible, as the permanganate itself has a very strong color. As we need some excess of the titrant, it makes sense to start with a blank test, to check what volume of excess titrant has to be added before the color change can be spotted.
In the case of iodometric titration, we use starch. Free iodine adsorbs at the starch surface, changing its color to blue. Depending on the titration type (and titrant) starch will either allow determination of the first traces of excess iodine, or determination of the moment when last traces of iodine disappear. In the latter case it is important to add starch close to the endpoint, as product of the iodine-starch reaction created when iodine concentration is high is relatively stable. Iodine itself is colored and its solutions are yellow, but intensity of the color is usually too low to be useful for endpoint detection.
In the case of bromine titration we can use methyl orange as an indicator - once the excess free bromine appears in the solution, it will oxidize the indicator and solution turns colorless. This is an example of application of irreversible redox indicator.
If you want to select an indicator for your method, you can try approach similar to that described in the acid-base titration end point detection section - calculate redox potential of your system for 99.9% and 100.1% titration and choose an indicator that changes color between these values.

Titration

Titration

Titration is a laboratory method of quantitative analysis used to determine unknown concentration of known substance.
Analysis is performed using burette - kind of laboratory glass made for exact measurement of volume of solution used.
The most popular titrimetric experiment is a determination of amount of acid.
Imagine you have a solution of a sulfuric acid of unknown concentration.
Pour exactly measured volume of sulfuric acid (VH2SO4) into a beaker and add few drops of alcoholic phenolphtalein solution. Solution will be colorless, as phenolphtalein becomes pink only in basic solutions (color becomes visible at pH above 8.2).
Now use burette to slowly add NaOH solution (called titrant) of known molar concentration CNaOH. pH slowly goes up. Once all sulfuric acid becomes neutralized one excess drop of strong base is enough to rapidly change pH of the solution and change its color to pink.

(Color change of phenolphthalein during titration - on the left, colorless solution before end point, on the right - pink solution after end point. )
When the color of the solution changes you know that you have neutralized all acid present - you have reached a titration end point. Using burette scale you may read volume of the titrant used (VNaOH).
We know that one mole of H2SO4 reacts with exactly two moles of NaOH:
2NaOH + H2SO4 → Na2SO4 + 2H2O
As we know that amount of substance of a given concentration in given volume of solution is n=C×V, we can write:
1 where 2 is a coefficient reflecting stoichiometry of the reaction equation. There is only one unknown in this equation:
2 So we have just determined concentration of unknown concentration of sulfuric acid.
Such stoichiometric calculation is the basis of all volumetric analytical methods. They differ when it comes to reagents used and methods of determination of the end point, but the general idea is always the same.
A volumetric determination can be no better than the equipment and technique used in performing it.

Acid-base titrations

Acid-base titrations

Acid-base titrations are based on the neutralization reaction. They are sometimes called alkalimetric titrations and general name of the method is alkalimetry, although these are not used as often as just "acid-base titration".
Acid-base titrations can be used to determine most acids and bases, strong and not too weak, monoprotic and polyprotic. For example we can use acid-base titration to determine concentration of hydrochloric acid, sulfuric acid, acetic acid, as well as bases - like sodium hydroxide, ammonia and so on. In some particular cases, when solution contains mixture of acids or bases of different strengths, it is even possible to determine in one titration composition of a mixture - for example sodium hydroxide and sodium hydrogen carbonate. Using acid-base back titration it is also possible to determine amount of substances that can be easily dissolved in acids, like calcium carbonate. To do so we would add known amount of hydrochloric acid to calcium carbonate and after the solid is dissolved we would titrate excess acid with a strong base.
Most commonly used reagents are hydrochloric acid and sodium hydroxide. Solutions of hydrochloric acid are stable, solutions of sodium hydroxide can dissolve glass and absorb carbon dioxide from the air, so they should be not stored for long periods of time.
There are many standard substances that can be used in acid base titrations. Those most popular are sodium carbonate Na2CO3, borax (disodium tetraborate decahydrate) Na2B4O7·10H2O and potassium hydrogen phthalate KHC8H4O4, often called simply KHP.
Type of indicator depends on several factors. One of them is the equivalence point pH. Depending on the titrated substance and titrant used this can vary, usually between 4 and 10. However, even if it is often possible (see list of pH indicators) we are rarely selecting indicator that changes color exactly at the equivalence point, as usually increase of accuracy doesn't justify additional costs. Thus in practice you will probably use phenolphtalein when NaOH is used as the titrant and methyl orange when titrating with the strong acid.

Remember, that what we calculate is not end point - but equivalence point.
In the equivalence point we have solution containing pure salt that is a product of the neutralization reaction occurring during titration. Thus calculation of equivalence point pH is identical with calculation of pH of salt solution.
Depending on the type of titration there are at least three different cases to discuss.
In the case of titration of strong acid with strong base (or strong base with strong acid) there is no hydrolysis and solution pH is neutral - 7.00 (at 25°C).
In the case of titration of weak acid with strong base, pH at the equivalence point is determined by the weak acid salt hydrolysis. That means we have to find pKb of conjugated base and calculate concentration of OH- starting from there, then use pH=14-pOH formula. See pH of weak acids and bases lecture and pH cheat sheet for details of calculation.
In the case of titration of weak base with strong acid, situation is very similar - pH at the equivalence point is determined by the weak base salt hydrolysis. Thus we need pKa of conjugated acid to calculate H+ and pH. Check lecture and cheat sheet mentioned above for details.
In the case of polyprotic acids and bases calculations get much harder. You may try to follow methods described in the lecture on polyprotic acids and bases pH calculation, or you may use BATE - pH calculator.
Calculate pH at the equivalence point of formic acid titration with NaOH, assuming both titrant and titrated acid concentrations are 0.1 M. pKa = 3.75.
At the equivalence point we have a solution of sodium formate. As both concentrations of titrated acid and titrant are identical, and monoprotic formic acid reacts 1:1 with sodium hydroxide, we have to add identical volume of base to the given volume of acid. That in turn means that final volume is twice that of initial volume of acid sample, so after dilution concentration of formate must be half that of acid - that is 0.05 M.
We have titrated weak acid, so to calculate pH we have to calculate concentration of OH- from formate hydrolysis first. Formate is a weak base with
1
Let's try to use the most simplified formula first:
2
Using 10-10.25 and 0.05 we get
3
To be sure we can use the simplified formula we have to check, whether hydrolysis was below 5%. To do so, we should divide concentration of OH- by initial concentration of formate. That means
4
Obviously assumption about low hydrolysis degree is correct, and we can proceed with calculation of pOH:
5
and pH:
6
What is pH at the equivalence point of 0.0211 M H2SO4 titrated with 0.01120 M NaOH?
7.0
OK, that was very short answer, now a little bit longer one. This is case of strong acid titrated with strong base, so we expect pH at equivalence point to be that of neutral solution - that is, 7.00. In reality the answer will be slightly different. Three reasons for that. First, sulfuric acid has pKa1 = -3 (very strong acid) but second dissociation step has pKa2 = 2.0, so it is much weaker. Still strong, but weak enough so that its hydrolysis can't be ignored, especially in more concentrated solutions. Second, NaOH - while strong base - is much weaker than it is commonly assumed, with pKb = 0.2 (see pKb of NaOH in ChemBuddy FAQ for details), so in precise calculations its hydrolysis can't be neglected as well. Finally, there is a reason that we are ignoring in all our examples, but that can't be neglected in the real lab - that is, activity coefficients of all ions involved are not 1 (more on that in ChemBuddy lecture on ionic strength and activity coefficients). If we take all these things into account we can calculate pH of the solution to be 7.05, close enough to 7.0.

PREFOMULATION

PREFOMULATION
The Concept of Preformulation:-
Almost all drugs are marketed as tablets, capsules or both. Prior to the development of these major dosage forms, it is essential that pertain fundamental physical and chemical properties of the drug molecule and other divided properties of the drug powder are determined. This information decides many of the subsequent events and approaches in formation development. This first learning phase is known as preformulation.
Definition:-
Preformulation involves the application of biopharmaceutical principles to the physicochemical parameters of drug substance are characterized with the goal of designing optimum drug delivery system.
Before beginning the formal preformulation programs the preformulation scientist must consider the following factors :-
- The amount of drug available.
- The physicochemical properties of the drug already known.
- Therapeutic category and anticipated dose of compound.
- The nature of information, a formulation should have or would like to have.
Preformulation drug characterization in a structured program:-
Test
Method/ function Characterization
Fundamental

1) UV spectroscopy
Simple assay
2) Solubility
Phase solubility/ purity
a) Aqueous
Intrinsic & pH effect
b) pKa
solubility control , salt formation
c) Salt
Solubility, hygroscopicity & stability
d)Solvents
Vehicles & Extraction
e) ko/ w
Lipophillicity, structure activity
f) Dissolution
Biopharmacy
3) Melting point
DSC-polymorphism hydrate & solvent
4) Assay development
UV, HPLC, TLC
5) Stability

In Solution
Thermal, hydrolysis, pH
In solid state
Oxidation, proteolysis metal ion
Derived

6) Microscopy
Particle size and morphology
7) Bulk density
Tablet and capsule formation
8) Flow properties
Tablet and capsule formation
9) Compression properties
Acid / excipient choice
10) Excipient compatibility
Preliminary screen by DSC, Conformation by TLC
UV Spectroscopy :-
The first requirement of any preformulation study is the development of a simple analytical method for quantitative estimation in subsequent steps. Most of drugs have aromatic rings and/or double bonds as part of their structure and absorb light in UV range, UV spectroscopy being a fairly accurate and simple method is a performed estimation technique at early preformulation stages. The absorption Co-efficient of the drug can be determined by the formula:-
E = AF / X
Where , A = Asborbance
F= dilution factor
X = weight of drug (mg)
It is now possible to determine connectration of drug in any solution by measuring absorbance.
C = AF / E mg/ ml
Characterization of drug molecules is very important step at the preformulation phase of product development. Following studies are conducted as basic preformulation studies, special studies are conducted depending on the type of dosage form and the type of drug molecules.
1) Solubility determination
2) pKa determination
3) Partition co-efficient
4) Crystal properties and polymorphism
5) Practical size, shape and surface area.
6) Chemical stability profile.
Solubility Determination:-
The solubility of drug is an important physicochemical property because it effects the bioavailabilty of the drug, the rate of drug resale into dissolution medium and consequently, the therapeutic efficiency of the pharmaceutical product.
The solubility of the molecules in various solvents is determined as a first step. This information is valuable is developing a formulation. Solubility is usually determined in variety of commonly used solvents and some oils if the molecules is lipophillic.
The solubility of material is usually determined by the equilibrium solubility method, which employs a saturated solution of the material, obtained by stirring an excess of material in the solvent for a prolonged until equilibrium achieved :-
Common solvents used for solubility determination are :-
·Water
·Polyethylene Glycols
·Propylene Glycol
·Glycerin
·Sorbitol
·Ethyl Alcohol
·Methanol
·Benzyl Alcohol
·Isopropyl Alcohol
·Tweens Polysorbates
·Castor Oil
·Peanut Oil
·Sesame Oil
·Buffer at various pHs
Aqueous Solubility :-
The availability of a drag is always limited and the preformulation scientist may only have 50 mg. Solubility dictates the ease with which formulation for oral gavages and intravenous injection studies in animals are obtained the pKa allives the informed of pH to maintain solubility and to choose salts required to achieve good bioavailability from the solid state and improve stability and powder properties.
Intensic Solubility (Co) :-
An increase in solubility in acid compared to aqueous solubility suggests a weak base and an increase in alkali, a weak acid . An increase in acidic and alkaline solubility suggest either impotence or zuitter ion behaviour. In this case there will be two pKa’s, one acidic & one basic . When the pavrity of the drug sample can be assured the solubility obtained in acid for a weak acid or albali for a weak base can be assured to be the instensic solubility (Co.) i.e. the fundamental solubility when completely unionized. The solubility should ideally be measured at two temperature.
1)4C to ensure physical stability and entered short term storage and chemical stability unit more definitive data are available. The minimum density of water occurs at 4C. This leads to a minimum aqueous solubility.
2)37C to support biopharmaceutral evaluation .
pKa Determination:-
Determination of the dissociation content for a drug capable of ionization within a ph rang of 1 to 10 is important since solubility and consequently absorption, cab be altered by orders of magnitude with changing pH. The Henderson – Hasseslebach equation provides an estimate of the ionized and un ionized durg concentration at a particular pH.
For acidic compounds
pH = pKa + log (un-ionized drug]) / [ionized drug])


Partition Coefficient :-
Partition Coefficient (oil/ water) is a measure of a drug’s lipophilicity and an indication of its ability to cross cell membranes. It is defined as the ratio of unionized drug distributed between the organic and aqueous phases at equilibrium.
P o/w = (C oil / C water) equilibrium.
For series of compounds, the partition coefficient can provide an empiric handle in screening for some biologic properties. For drug delivery, the lipophilic/ hydrophilic balance has been shown to be a contributing factor for the rate and extent of drug absorption. Although partition coefficient data alone does not provide understanding of in vivo absorption, it does provide a means of characterizing the lipophilic/ hydrophilic nature of the drug.
Since biological membranes are lipoidal in nature. The rate of drug transfer for passively absorbed drugs is directly related to the lipophilicity of the molecule. The partition coefficient is commonly determined using an oil phase of octanol or chloroform and water.
Drugs having values if P much greater than 1 are classified as lipophilic, whereas those with partition coefficient much less than 1 are indicative of a hydrophilic drug.
Although it appears that the partition coefficient may be the best predictor of absorption rate, the effect id dissolution rate, pKa and solubility on absorption must not be neglected.
Dissolution :-
The dissolution rate of the a drug is only important where it is the rate limiting step in the absorption process. Kaplan suggested that provided the solubility of a drug exceded to mg/ ml at pH , 7 no bioavailability or distinction related problems were to be expected. Below / mg/ ml such problems were quite possible and salt formation could improve absorption and solubility by controlling the pH of the microenvironment, independently of the drug and dosage forms position within the GI ireat.
Intrinsic Dissolution Rate :-
When dissolution is controlled solely by diffusion the rate of diffusion is directly proportional to the saturated concentration of the drug in solution under these conditions the rate constant K1 is defined by
K1 = 0.62 D2/3 v 1/6 w1/2
Where, V is the kinemative viscosity
W is the anguter velocity of a rotating disc of drug.
Common Ion Effect :-
A common ion significantly reduces, the solubility of a slightly soluble electrolyte. The ‘selling out’ results from the removal of water molecules as solvent owing to the completing hydration of other ions. The reverse process ‘salting in’ qries with large anions e.g. benzoate, salivate which open the water structure. These hydro topics increase the solubility of properly water soluble compounds such as diazepam.
Melting Point :-
The melting point of a drug can be measured using three techniques :-
1)Capillary Melting
2)Hot Stage Microcopy
3)Differential scanning calorinetry or thermal Anaylysis.
Capillary Melting :-
Capillary melting gives information about the melting range but it is different to assign an accurate melting point.
Hot Stage Microcopy :-
This the issued observation of melting under a microscope equipped with a heated and lagged sample stage. The heating rate is controllable and upto three transitions can e registered.
Differential Scanning Calorimeltry and thermal analysis :-
Differential thermal analysis (DTA) measures the temperature difference between the sample and a reference as a function of temperature or time when heating at a constant rate differential scanning calorinetry (DSC) is similar to DTA except that the instrument measures the amount of energy required to keep the sample at the same temperature as the reference i.e. it measures the enthalpy of transition.
Crystal Properties and Polymorphism :-
Many drug substance can exit in more than one crystalline from with different space lattice arrangements. This property is known as polymorphism. Polymorphs generally have diffrent melting points, x-ray diffraction patterns and solubility even though they are chemically identical.
Differences in the dissolution rates and solubilities of different polymorphic forms of a given drug are very commonly observed. When the absorption of a drug is dissolution rate limited, a more soluble and faster-dissolving from may be utilized to improve the rate and extent of bioavailability.
For drugs pane to degradation in the solid state, physical form of the drug influences degradation. Selection of a polymorph that is chemically more stable is a solution in many cases. Different polymorph also lead to different morphology, tensile strength and density of power bed which all contribute of compression characteristics of materials. Some investigation of polymorphism and crystal habit of a drug substance as it relates to pharmaceutical processing is desirable during its Preformulation evaluation especially when the active ingredient is expected to constitute the bulk of the tablet mass. Although a drug substance may exist in two or more polymorphic forms, only one form is theromdynamically stable at a given temperature and pressure. The other forms would convert to the stable form with time. In general, the stable polymorph exhibits the highest melting point , the lowest solubility, and the maximum chemical stability. Various techniques are available for the investigation of the solid state. These include microscopy (including hot stage microcopy), infrared spectrophotometry, single-crystal x-ray and x-ray power diffraction, thermal analysis, and dilalometry.
Particle Size, Shape and Surface Area:-
Bulk flow, formulation homogeneity, and surface-area controlled processes such as dissolution and Surface morphology of the drug particles. In general, each new drug candidate should be tested during Preformulation with the smallest particle size as is practical to facilitate preparation of homogeneous samples and maximize the drug’ s surface area for interactions.
Various chemical and physical properties of drug substances are affected by their particle size distribution and shapes. The effect is not only on the physical properties of solid drugs but also, in some instances, on their biopharmaceutical behavior. It is generally recognized that poorly soluble drugs showing a dissolution- rate limiting step in the absorption process will be more readily bio available when administered in a finely subdivided state rather than as a coarse material.
In case of tablets, size and shape influence the flow and the mixing efficiency of powders and granules. Size can also be a factor in stability: fine materials are relatively more open to attack from atmospheric oxygen, the humidity, and interacting axcipients than are coarse materials.
- Determination of particle size
-Determination of surface area
Particle size Determination:-
Though microscopy is the simplest technique of estimating size ranges and shapes, it is to slow for quantitative determination the material is best observed as a suspension in non dissolving fluid. Saving is less useful technique at preformulation storage due to lack of bulk material. Andreason pipette is based on the rate difference of sedimentation of different particles, but techniques like this are seldom used due to their tedious nature instruments based on light scattering, (Royco), light blockage (HIAC) and blockage of electrical conductivity path (coulter counter) are available.
Surface Area Determination:-
Surface area is most commonly determined based on brunaver emette teller (BET) theory of adsorption. Most substances adsorb a mono molecular layer of gas under certain conditions of partial pressure of gas and temperature. Knowing the monolayer capacity of adsorbent and the area of absorbale molecule, the surface area can be calculated the adsorption process is carried out with nitrogen at-195 degree Celsius at a partial pressure attainable when nitrogen is in a 30% temperature with an inert gas (helium). The adsorption takes place by virtue of vander wall’s forces.
Power Flow Properties:-
When limited amounts of drugs are available Power flow properties can be evaluated by measurements of bulk density and angle of repose. Changes in particles size, and shape are generally very important an increase in crystal size or a more uniform shape will lead to a small angle or rpose and a smaller Carr’s index.
Bulk Density :-
Knowledge of absolute and bulk density of the drug substance is Very useful in Having some idea as to the size of final dosage form the density of solids also of affects their flow Properties Carr’s compressibility index can be used to predict the flow properties based on density measurement.

Carr’s index (%) = Tapped density – Pored density *100
Tapped density
A similar index has been defined by Hausner :
Hausner ratio = Tapped density
Pored density
Angle of repose:-
The maximum angle which is formed b/w the surface of a pile of powder and horizontal surface is called the angle of repose.
Relationship between flow, angle of repose, Carr’s index fee power flow
Flow
Angle of repose
Carr’s index ( % )
Excellent
<25
5-15
Good
25-30
12-16
Fair to passable
30-40
18-21
Poor
> 40
23-35
Very Poor

33-38
Extremely Poor

>40
Chemical stability profile:
Preformulation stability studies are usually the first quantitative assessment of chemical stability of a new drug. These studies include both solution and solid state experiments under condition typical for the handing, formulation, storage, and administration of a drug candidate as well as stability in presence of other recipients.
Factor effecting chemical stability critical in rational dosage form design include temperature, pH and dosage form diluents. The method of sterilization of potential product will be largely dependent on the temperature stability of the drug. Drugs having decreased stability at elevated temperatures cannot be sterilized by autoclaving but must be sterilized by another means, e.g., filtration. The effect of pH on drug stability is important in the development of both oral administration must be protected from the highly acidic environment of the stomach. Buffer selection for potential dosage forms will be largely based on the stability characteristic of the drug.

- Solid state stability
- Solution phase stability
- Compatibility studies : stability in the Presence of excipients
- Typical stability protocol for anew Chemical Entity
Solid state stability:-
Chemical instability normally results from either of the following reaction :- hydrolysis, oxidation, photolysis and pyrolysis, Chemical structure of the drug is the determination of drug to either of these attacks. Esters and lactase and to lesser extent, amides are to prone to solvolysis . Instauration or electron rich centre in the structure make the molecule vulnerable for free radical mediated or photo-catalysed oxidation. physical properties of drugs. Amorphous materials are less stable than their crystalline forms. Denser materials are more stable to ambient stress.
Elevated temperature studies:-
The elevated temperatures commonly used are 40, 50, and 60 degree centigrade with ambient humidity. The samples stored at highest temperature are observed weekly for physical and chemical changes and compared to an appropriate control . If a substantial change is seen, samples stored at lower temperature are examined . If no changesisseen after 30 days at 60 degree centigrade, the stability prognosis is excellent .


Stability under high humidity conditions :-
Solid drug samples can be exposed to different relative humidity conditions by keeping them in laboratory desiccators containing saturated solutions of various salts. The closed desiccators in turn are kept in oven to provide constant temperature. The preformulation data of this nature are useful in determining if the material should be protected and stored in controlled low humidity environment or if non aqueous solvent be used during formulation.
Photolytic stability :-
Many drugs fade or dorpen on exposure light. Though the extent of degradations small and limited to the exposed surface area, it presentsanaesthetic problem. Exposure of drug 400 and 900 foot-candles of illumination for 4 and 2 week periods respectively is adequate to provide some idea of photosensitivity. Resulting data may be useful in determining if an amber colored container is required or if color masking bye should be used in the formulation .
Stability to Oxidation :-
Drug’s sensitivity to oxidation can be examined by exposing it to atmosphere of high oxygen tension. Usually a 40% oxygen atmosphere allows for rapid evaluation. A shallow layer of drug exposed to a sufficient headspace volume ensures that the system is not oxygen limited. Samples are kept in desiccators equipped with three-way stop cocks, which are alternatively evacuated and flooded with desired atmosphere. The process is repeated 3 or 4 times to ensure 100% desired atmosphere. Results may be useful in predicting if an antioxidant is required in the formulation or if the final product should be packaged under inert atmospheric conditions.
Compatibility studies :-
The knowledge of drug excipients interaction is useful for the formulation to select appropriate excipients. The described preformulation screening of drug excipients interaction requires only 5mg of drug in a 50% mixture with the excipients to maximize the likelihood of obscuring an interaction . Mixtures should be examined under nitrogen to ultimate oxidation and paralytic effect at a standard heating rate on DSC, over a temperature range, which will encompass any thermal changes due to both the drug and appearance or disappearance one or more peaks in themogrames of drug excipient mixtures are considered of indication of interaction.
Solution phase stability:
As compared with the dry form, the degradation is much rapid in solution form. It is important ascertain that the drug doesn’t degrade when exposed to GI fluid. The pH based stability study, using different stimulator GI condition can be designed. A poor solution stability of drug may urge the formulator to choose a less soluble salt form, provided the bioavailability is not compromised


Absorption behavior:
It is essential to test the in vivo behavior of the new drug for successful formulation of a dosage from good bioavailability. Partial in vivo and in vitro test are designed to study pharmacokinetic profile of the drug.
Conclusion:
Preformulation studies have a significant part to play in anticipating formulation problems and identifying logical path in both liquid and solid dosage form technology. The need for adequate drug solubility can not be overemphasized. The most appropriate salt for development. Stability studies in solution will indicate the feasibility of parental or other liquid dosage form and can identify methods of stabilization. In parallel solid-state stability by DSC, TLC and HPLC in the presence of tablet and capsule excipient will indicate the most acceptable vehicles for solid dosage form.
By comparing the physicochemical properties of each drug candidate with in a therapeutic group, the preformulation scientist can assist the synthetic chemist to identify the optimum molecule, provide the biologist with suitable vehicles to elicit pharmacological response and advise the bulk chemist about the selection and production of the best salt with appropriate particle size and morphology for subsequent processing.

Rajiv Gandhi Proudyogiki Vishwavidalaya, Bhopal (M.P.)B. PHARMA-IV SEMESTER

Pharmaceutics- IV (Pharmaceutical Engineering – II) (PY-401)
Size Reduction and Size Separation- Definition objectives and significance of size
reduction, Factors affecting size reduction, Standard of powders, Sieves and their usage
in grading of powders, Laws governing energy and power requirements of a mill,
Classification of size reduction machines, Study of various types of mill including ball
mill, hammer mill fluid energy mill energy mill etc. Fluid classification methods.
Evaporation-Basic concepts, Factors affecting evaporation, Types of evaporators, Study
of short tubs evaporators, Forced circulation evaporators and Film evaporators, Single
and multiple effect evaporation, Evaporation under reduced pressure, Evaporation
capacity, Heat and material balance, Scale formation, Foam and entrainment.
Distillation- General theory applied to binary mixtures, Boiling point and equilibrium
diagrams, Raout’s Law and Henry’s Law, Constant boiling mixtures, Simple, steam and
Equilibrium distillations, Rectification, Constructions of rectifying columns. Analysis of
rectifying column: McCabe Thiel method and Lewis Sorel method for calculation of
number of theoretical plates, Azeotropic and extractive distillations.
Drying- Introduction, Theory of drying Rate of drying curves, Classification of dryers,
Study of dryers used in pharmaceutical industries, Special drying methods.
Extraction- Principles of solid-liquid and liquid- liquid extraction, Theories of extraction
of drugs, Diffusion battery, Podbielnaik extractor, Continuous counter- current
extraction system.
Crystallization-Importance of crystal purity, size, shape, geometry habit forms and
types, Solubility curves and calculation of yields, Mier,s supersaturation theory and its
limitations, Nucleation and crystal growth, Classification of crystallizers, Principles
underlying the design and operation of Tank, Swenson-walker, Krystal and Vacuum
crystallizer, Crystallizer employed for producing large crystals, Caking of crystals and its
prevention.
Mixing-Theory of mixing, Solid-solid; solid-liquid and liquid-liquid mixers used in
pharmaceutical industries.
Filtration and Centrifugation- Theory of filtration, Factors affecting filtration, Filter
media, Filter aids, Classification of filters, Industrial filters including Filter press, Rotary
filter, Membrane filter etc.
Principles of centrifugation, Industrial filters and centrifugation sedimenters.
Compaction and Compression- Adhesion and Cohesion of particles, Strength of
granules, Factors affecting strength of tablets, Physics of tablet compression.
Pilot Plant Scale Up Techniques- Concepts of pilot plant, scale up techniques in
pharmaceutical industries.
Books recommended
1 Elementary Chemical Engineering - Max S. Peters, Published by McGraw Hill Book
Company, New York, 1954.
2 Perry’s Chemical Engineer’s Handbook - Robert H Perry, Green D.W., Maloney O.7th
Edition, 1998, McGraw – Hill Inc., New York.
3 Tutorial Pharmacy by Cooper & Gunn, ed. S.J.Carter, CBS Publishers & Distributors,
Delhi, 6th Edition, 2000.
4. Unit Operations of Chemical Engineering, 5th edition – McCabe, Smith & Harriott,
McGraw – Hill Inc., New York.
5 Pharmaceutical Engineering – K.Sambamurthy, 2002 NAI (P) Ltd., Delhi.
6 Pharmaceutics : The Science of Dosage Form Design - M.E. Aulton.
7 The Theory & Practice of Industrial Pharmacy – Lachman L., Lieberman H.A. &
Kanjig J.L., 3rd edition, 1990 Varghese Publishing House, Bombay.
8 Alfonso G. Remington: The Science & Practice of Pharmacy. Vol.I & II. Lippincott,
Williams & Wilkins Philadelphia.
9 Jani G. K., Pharmaceutics II (Unit Operations), B. S. Shah Prakashan, Ahmedabad.
10 Subramanyam C.V.S., Thimma J, Suresh S.S. et. al., Pharmaceutical Engineering :
Principles and Practice, 2002, Vallabh Prakashan, Delhi.
11 Introduction to Chemical Engineering by Walter L. Badger & Julius T. Banchero,
Mcgraw Hill International edition, New Delhi, 1955.
12 Filtration in Pharma. Industry by Theodore H. Meltzer, Marcel Dekker Inc.,
New York, 1987.
13. A. R. Paradkar, Introduction to Pharmaceutical Engineering, Nirali Prakashan, 10
th
Ed. 2007.
List of practicals
PY401 Pharmaceutics – IV (any twelve)
1. Study the effect of diameter of balls, No. of balls volume of balls or feed amount
on the particle size reduction wing ball mill.
2. Calculate the energy requirement (as per Riltinger’s law) for the powder milling.
3. Study the particle size distribution the given sample using standard sieve method.
4. Determine the particle size distribution of a given sample using microscopy.
5. Study the rate of sedimentation of the given sample.
6. Study the effect of suspending agents on the rate of sedimentation of the given
sample.
7. Compare the efficiency of different suspending agents on the rate of
sedimentation of the given sample.
8. Study the effect of temperature, surface area and viscosity of the liquid on the rate
of evaporation.
9. Construct the boiling point diagram for the given mixture of alcohol and water.
10. Separate the constituents of the given a zeotropic mixture by the addition of third
agent.
11. Study the rate of drying and determine EMC, CMC and FMC.
12. Study the effect of surface area, material bed thickness, temperature and moisture
content on the rate of drying.
13. Compare the efficiency of single stage extraction with multiple stage extraction.
14. Determine the percentage of acetic acid extracted from the mixture of benzene
and acetic acid using water as our extracting agent.
15. Prepare mier’s super solubility curve for the given samples.
16. Determine the percentage purity of the given sample using crystallization
technique.
17. Determine the mixing index for the mixing of give powders.
18. Determine the effect of surface area, thickness of filter medium, viscosity of
liquid, temperature and filter aid on the rate of filtration.
Pharmaceutics –V (Dosage Form Design) (PY- 402)
Pharmaceutical preformulation: -
Definition and scope,
Establishment and importance of following physicochemical parameters
Solubility, pKa and selection of suitable salt, partition coefficient, dissolution,
polymorphism, microscopy and powder properties, stability and drug-excipient
compatibility Pharmaceutical factors influencing drug formulation.
Study of different types of formulation additives:
Diluents, Binders, Disintegrating agents, Lubricants, Solvents, Co-solvents and Vehicles,
Preservatives, Suspending agents, Emulsifying agents, Antioxidants, Preservatives,
colouring, flavoring and sweetning agents, Viscosity enhancers, ointment and
suppositories bases
Polymers and biodegradable polymers:
Classification, Methods of synthesis, Properties, Characterization and evaluation.
Brief introduction of biodegradable polymers, pharmaceutical applications of polymers..
Dissolution stability and degradation study:
Chemical stability, pathways of degradation, physical and phase transformation, stability
testing protocols for various pharmaceutical dosage forms, determination of expiry date
(shelf life) and overage calculations, stabilization of pharmaceutical formulations.
Drug product design:
Stages of drug discovery and development process, Importance of product design,
considerations.
Dissolution technology:
Theories of dissolution, factors affecting dissolution, design of various dissolution
apparatus, dissolution media, dissolution testing of different types of dosage
formulations, data interpretation, mathematical models for predication of dissolution of
profile.
List of practicals:
(Any ten)
1. Establish the following preformulation parameters of the given drug sample.
(a) Melting point (b) solubility (c) intrinsic solubility (d) pKa (e) Partition coefficient
2. Establish the following preformulation parameters of the given drug sample.
(a) Particle size distribution (b) Flow proportion (c) Bulk deurity (d) Carr’s index (e)
Compression preparation.
3. Study the drug excipient compatibility of given drug with commonly used
excipent by TLC technique.
4. Estimate the self life of the given drug
5. Study the effect of mesture content on chemical stability of aspirin.
6. Study the effect of temperation on stability of given photosensitive drug.
7. Determine the molecular Mass of given polymer by viscometer.
8. Perform the in-vitro dissolution study of given the sample of tablet.
9. Study the effect of presence of surfactant in dissolution of tablet cantoning poorly
soluble drug.
10. Study the effect of solvent / co-solvent hydrotropic agents on solubility of given
drug.
11. Study the effect of pH of dissolution on in-vitro dissuasion study.
12. Compare the dissolution profile of two marketed tablet products.
References:
1. Swarbrick J., Boylan J.C., Encydopedia of Pharmaceutical Technology, Second
edition, Volume-1,2,3, Marcel Dekker, Inc. Newyork.
2. Qice yihong, ChenY, Zhang G.G.Z., Developing solid Oral dosage forms-
Pharmaceutical Theory and Practice charon Tech Ltd.
3. Allen L.V., Popovich N.G., Ansel H.C., Ansel’s Pharmaceutics design and drug
delivery systems, Eight edition, B.I. Publication Pvt. Ltd.
4. Aulton M.E. Pharmaceutics- The science of dosage form design” second edition.,
Churchill Livingstone Pvt. Ltd.
5. Banker G.S., Rhodes C.T., Modern Pharmaceutics” second edition, Marcel
Dekker, Inc., Newyork.
6. Kanig J.J., Liebermen H.A., Lachman L. “The theory and Practics of Industrial
Pharmacy, Varghese Publishing House, Bombay.
7. Rowe RC, Sheskey P.J., Owen S.C., Handbook of Pharmaceutical Excipents,
Fifth edition, Pharmaceutical Pr.
8. Bugay D.E., Findlay W.P., Pharmaceutical Excipents, Marcel Dekker, Inc.
Newyork.
9. Kim C.J., Advanced Pharmaceutics- Physiochemical Principle CRC Press,
Florida.
10. Jan N.K., Pharmaceutical Product Development, CBS Publishers and distributors,
New Delhi.
11. Shah D.H., “SOP Guidelines”, Business Horizons Publishers, New Delhi.
12. Wachter A.H., Nash R.A., “Pharmaceutical Process validation, Marcel Dekker,
Inc. Newyork.
13. Mazzo D.J., “International stability Testing” Interpha Press, Inc. Illinois.
14. Gibaldi M., Perriner D., “Pharmacokinetics:, Marcel Dekker Newyork.
BRANCH: PHARMACY-IV SEMESTER
COURSE: PY 403 PHARMACEUTICAL ANALYSIS (THEORY)
Fundamentals, Significance of quantitative analysis in quality control, Different techniques of analysis.
Theoretical considerations and pharmaceutical applications; with special reference to Indian
pharmacopoeia; of the following analytical techniques -
1) Acid-Base titrations: Theoretical principles. Classification, Direct titration of strong acids, Strong
bases, and weak bases, Back titrations, Acid –Base indicators, Choice of indicators and mixed
indicators. Methods for determination of organically combined Nitrogen and in pharmaceutical
applications.
2) Oxidation-Reduction titrations: Concepts of oxidation and reduction, redox reactions, strengths &
equivalent weighs of oxidizing and reducing agents, redox indicators, potassium permanganate
titrations, iodometry & iodometry, 9£dcammonium sulphate titrations, potassium iodate titrations.
Pharmaceutical applications, preparation and standardization of redox titrants e.g. sodium thiosulphate
etc.
3) Precipitation titrations: Detection of End Points in Precipitation reactions. Indicators used in
Precipitation titrations, Preparation & standardization of titrants like silver nitrate, ammonium
thiocyanate; titrations according to Mohr's and Volhard's methods; ammonium and potassium
thiocyanate titrations; indicators; applications in pharmaceutical analysis
4) Gravimetric analysis: Fundamentals of gravimetry, Precipitation reagents precipitation techniques,
Specific examples of gravimetric estimation like Aluminum as hydroxy quinolate, Barium on Barium
Sulfate, Lead as Chromate and Magnesium as Magnesium Pyrophosphate.
5) Non-aqueous titrations: Scopes and limitations, Solvents used in non aqueous titrations. Acid-base
equilibria in non-aqueous media, Titration of weak acids and weak bases with specific examples given
in Indian Pharmacopoeia.
6) Complexometric titrations: Theory of Complexometric analysis. Factor in influencing stability of
complexes. pM indicators. Types of Disodium edetate titrations with suitable examples.
7) Conductometry: Ohm’s law and ionic conductivities, Apparatus used for conductimetric titrations.
Application of conductimetry in acid-base, Precipitation and complexometric titrations with suitable
examples.
8) Potentiometry: Theory and principles, Reference electrodes, Indicators electrodes and Ion selective
electrodes. Instrumentation for potentiometric titrations. Application of potentiometry for end point
determination in acid-base titration, redox titrations, precipitation titrations with suitable examples
9) Polarography & Amperometry: Introduction, theoretical principles, organic polarography, dropping
mercury electrode, basic principles of polarographic instruments, methods of analysis, experiments
including amperometric titrations.
10) Miscellaneous methods of analysis like diazotization titrations and Karl-fisher titrations.
List of Practicals:
A total of 15 experiments should be performed on the topics mentioned below
1. Acid base titrations: Preparation and standardization of acids and bases, some exercises related to
the determination of acids and bases separately and in mixture form. Some official assay procedures of
boric acid, ascorbic acid shall also be covered.
2. Oxidation-reduction titration: Preparation and standardization of some redox titrants, e.g.,
potassium permanganate, potassium dichromate, iodine, sodium thiosulphate etc. Some exercises
related to the determination of oxidizing and reducing agents in the sample shall be covered. Exercises
involving use of potassium iodate, potassium bromate, ceric ammonium sulphate shall be performed.
3. Precipitation titrations: Preparation and standardization of titrants like silver nitrate and ammonium
thiocyanate, titrations according to Mohr's and Volhard's methods.
4. Gravimetric analysis: Determination of water of hydration, some exercises related to Gravimetric
estimation of metal ions such as barium, magnesium and calcium shall he covered.
5. Diazotization reaction: Assay of sulphonamides.
6. Complexometric titration: Any two official assays done by this method.
7. Non-aqueous titrations: preparation and standardization of some non aqueous titrants, e.g.,
Perchloric acid, tetrabutyl ammonium hydroxide. Any two official assay given in Pharmacopoeia of
India.
BOOKS RECOMMENDED
1. A.H. Beckett and J.B. Stenlake: Practical Pharmaceutical Chemistry, Vol I and II, CBS Publishers
and Distributors, New Delhi, India
2. H. H. Willard, L. L. Merritt and J. A. Dean: Instrumental Methods of Analysis, Van Nostrand
Reinbold, New York.
3. L.M. Atherden: Bentley and Driver's Text book of Pharmaceutical Chemistry, Oxford
UniversityPress, Delhi.
4. G.L. Jenldns, J.E. Christian, G.P. Hager: Quantitative Pharmaceutical Chemistry, McGrawHill,
Company, New York.
5. Pharmacopoeia of India, Govt. of India, Ministry of Health, Delhi.
6. Bassett, R.C. Denney, G.H. Jeffery, J. Mendham: Vogel's Textbook of quantitative Inorganic
Analysis, The ELBS and Longman, London.
Course Contents
Category of
Course
Course Title Course
Code
Credit-4C Theory Paper
(ES)
Pharmaceutical L T P
Chemistry-V
(Biochemistry) (Theory)
PY 404
4 0 3
Max.Marks-70
Duration-3hrs.
Branch: Pharmacy-IV Semester
Course: PY -404 Pharmaceutical Chemistry-V (Biochemistry) Theory
Biochemical organization of the cell and transport processes across cell membrane.
The concept of free energy, determination of charges in free energy system from
equilibrium constant and reduction potential, bioenergetics, production of ATP and its
biological significance.
Structure and Functions of Proteins:
Amino acids and Peptides, Determination of Primary structure and higher orders of
structure.
Enzymes:
Nomenclature, Kinetics ans its Mechanism of action, Mechanism of
Inhibition,Isoenzymes, enzymes in technical diagnosis.
Co-enzymes:
Metals as coenzymes and their significance and Vitamins as coenzymes and their
significance.
Carbohydrate Metabolism:
Conversion of Polysaccharide to Glucose 1-Phosphate, Glycolysis and Fermentation and
their regulation, Gluconeogenesis and Glycogenolysis, metabolism of galactose and
galactosemia, role of sugar nucleotide in biosynthesis, pentosephosphate pathway.
The Citric acid cycle:
The significance, reaction and energetics of cycle, amphibolic role of cycle, Glyoxalic
Acid Cycle.
Lipid Metabolism:
Oxidation of fatty acids, Beta Oxidation and energetic, alpha oxidation,omega oxidation,
Biosynthesis of Ketone bodies and their utilisation, Biosynthesis of saturated and
unsaturated fatty acids and eicosanoids, phospholipids, sphingolipids.
Biological oxidation:
Redox Potential, enzymes and co-enzymes involved in oxidation reduction and its
control. The respiratory chain, its role in energy capture and its control, energetic of
oxidative phosphorylation, inhibitors of respiratory chain and oxidative phosphyrlation,
mechanism of oxidative phosphorylation.
Nitrogen & Sulphur Cycle:
Nitrogen fixation, ammonia assimilation, sulphur activation, sulphate reduction,
incorporation of sulphur in organic compounds, release of sulphur from organic
compounds
Metabolism of Ammonia and Nitrogen Containing monomers:
Nitrogen balance, biosynthesis of amino acids, catabolism of amino acids, conversion of
amino acids to specialized products, assimilation of ammonia , urea cycle, metabolic
disorders of urea cycle, metabolism biosynthesis, formation of bile pigment,
hyperbilirubinemia, purine biosynthesis, purine nucleotide interconversion, pyrimidine
biosynthesis, and formation of deoxyribonucleotides.
Disorders of Carbohydrate, Lipid and Protein Metabolism:
Biomedical Importance and Implications in Clinical Biochemistry. Diagnostic tests for
detection of metabolic disorders.
Biosynthesis of nucleic Acids:
Brief introduction to genetic organisation, organisation of mammalian genome, alteration
and rearrangement of genetic material, biosynthesis of DNA and its replication, mutation,
physical and chemical mutagenesis/ carcinogenesis, DNA repair mechanism, biosynthesis
of RNA.
Genetic code and Protein synthesis:
Genetic code, Components of protein synthesis and inhibition of protein synthesis. Brief
account of genetic engineering and polymerase chain reactions. Regulation of gene
expression.
Course Contents
Category of
Course
Course Title Course
Code
Credit
Pharmaceutical Chemistry-V L T P
(Biochemistry) Practical
PY 404
4 0 3
Branch: Pharmacy IV Semester
Course: PY- 404 Pharmaceutical Chemistry-V(Biochemistry) Practical
PY-404 PHARMACEUTICAL CHEMISTRY-V
(BIOCHEMISTRY) PRACTICAL
1. Qualitative and Quantitative chemical examination of Urine ,Blood and Faeces.
2. Food Analysis – Analysis of Milk ,Butter, Flour, Honey and Starch.
3. Systemic analysis of water for pharmaceutical purpose.
4. Seperation of amino acids by two dimensional paper chromatography and gel
electrophoresis.
5. Seperation of lipids by TLC.
6. Seperation of Serum protiens by electrophoresis on cellulose acetate.
7. Quantitative estimation of amino acids and proteins.
8. Determination of glucose.
9. Isolation and determination of RNA and DNA.
Books Recommended
1. Martin, D.W., Mays, P.A. and Redwell, V.M., Harper’s Review of Biochemistry,
Lange medical Publication.
2. Horrow, B. and Mazur, A., Text book of biochemistry, W.B. Saunders Co.
Philadelphia.
3. Lehninger, A.L., Principles of Biochemistry, CBS Publishers and Distributors.
4. Lehninger, A.L., Biochemistry, Worth Publishers Inc.
5. Stryer, L., Biochemistry, W.H. Freeman and Co. San Franscisco.
6. Plumer, D.T., An Introduction to Practical Biochemistry, Tata McGraw Hill, New
Delhi.
7. Jayaraman, J., Laboratory manual in Biochemistry, Wiley eastern Ltd., New
Delhi.
Course Contents
Category of
Course
Course Title Course
Code
Credit-4C Theory Paper
(ES)
Pharmacology-I PY 405 L T P
4 0 0
Max.Marks-70
Duration-3hrs.
Branch: Pharmacy-IV Semester
Course: PY - 405 Pharmacology-I (Theory)
General Pharmacology
a. Introduction to pharmacology, sources of drugs, dosage forms and routes of
administration, mechanism of action, combined effects of drugs, factors
modifying drug action, tolerance and dependence, pharmacogenetics.
b. Absorption, distribution and excretion of drugs, principle of basic and clinical
pharmacokinetics adverse drug reactions and treatment of poisoning, ADME drug
interaction, bioassay of drugs and biological standardization, discovery and
development of new drugs. Introduction to clinical trials.
Pharmacology of Peripheral Nervous System
a. Neurohumoral transmission (autonomous and somatic)
b. Parasympathomimetic, parasympatholytic, sympathomimetics, sympatholytics,
neuron blocking agents.
c. Neuromuscular blocking agents
d. Local anaesthetic agents
Autocoids
a. Histamine, bradykinin 5- HT and their antagonists.
b. Prostaglandins, leukotrienes and platelet activating factors.
Analgesic, Antipyretic, Anti-inflammatory and Anti-Gout Drugs:
Drugs acting on Respiratory System and Pathophysiology of respiratory system:
a. Anti-asthmatic drugs including bronchodilators
b. Anti-tussives and expectorants
Books Recommended
1. Satoskar, R.S. and Bhandarkar, S.D., Pharmacology and Pharmacotherapeutics.
2. Tripathi, K.D., Essentials of Medical Pharmcology.
3. Kulkarni, S.K., Handbook of Experimental Pharmacology, Vallabh Prakashan, New
Delhi.
4. Crossland, J and Thomson, J.H., Essential of Pharmacology, Harper and Row,
Publishers, New York.
5. Craig, C.R. and Stitzel, R.R., Modern Pharmacology, Little Brown and Company.
6. Rang, M.P. , Dale, M.M. and Riter, J.M., Pharmacology, Churchill Livingstone.
7. Paul, L., Principles of Pharmacology, Chamman and Hall.
8. Herfindal, E.T. and Hirschman, J.L., Clinical Pharmacy and Therapeutics, William
and Wilkins.
9. Katzung, B.G., Basic and Clinical Pharmacology, Prentice Hall International.
Course Contents
Category of
Course
Course Title Course
Code
Credit
Pharmacology-I PY 405 L T P
0 0 3
Branch: Pharmacy V Semester
Course: PY 405 Pharmacology-I - Practical
V-P-1 PHARMACOLOGY I PRACTICALS
List of practicals:
1. Introduction to Experimental Pharmacology and various regulatory authorities.
2. Study of common laboratory animals and anesthetics used in animal studies.
3. Study of various routes of drug administration in experimental animals.
4. Preparation of various physiological salt solution and set up of isolated rat ileum
preparation.
5. Study the effects of various agonists and antagonists on isolated rat ileum
preparation.
6. Plot dose response curve of choline using isolated gunea pig ileum preparation.
7. Plot dose response curve of histamine using isolated guinea pig ileum preparation.
8. Study the effect of autonomic drugs mydriatic and miotic on rabbit eye.
9. Study the effect of local anesthetics on rabbit eye.
10. Study the peripheral analgesic activity of indomethacin using writhing test on
mice.
11. Study anti- inflammatory activity of indomethacin using rat paw edema paradigm.
12. Study the neuromuscular effect of d-tubocurarine/ succinyl choline using rotarod
apparatus.
Books recommended
1. Hardmen, J.G., Limbired, L.E., Molinoss, P.B., Ruddon, R.W. and Gil, A.G.,
Goodman and Gillman’s The Pharmacological basis of Therapeutics, Pergamon
Press.
2. Satoskar, R.S. and Bhandarkar, S.D., Pharmacology and Pharmacotherapeutics.
3. Tripathi, K.D., Essentials of Medical Pharmcology.
4. Kulkarni, S.K., Handbook of Experimental Pharmacology, Vallabh Prakashan, New
Delhi.
5. Crossland, J and Thomson, J.H., Essential of Pharmacology, Harper and Row,
Publishers, New York.
6. Craig, C.R. and Stitzel, R.R., Modern Pharmacology, Little Brown and Company.
7. Rang, M.P. , Dale, M.M. and Riter, J.M., Pharmacology, Churchill Livingstone.
8. Paul, L., Principles of Pharmacology, Chamman and Hall.
9. Herfindal, E.T. and Hirschman, J.L., Clinical Pharmacy and Therapeutics, William
and Wilkins. Katzung, B.G., Basic and Clinical Pharmacology, Prentice Hall
International.

DEFINITIONS OF DOSAGE FORMS

(Note: Dosage forms defined earlier are not defined here)

1. Applications: These are fluids or semi-fluid preparations intended for application to the skin.

2. Cachets: Cachets are moulded from rice paper, a material made by pouring a mixture of rice flour and water between two hot polished revolving cylinders; these are used to enclose the nauseous or disagreeable powders in tasteless powders for administration.

3. Collodions: These are fluid preparations for external use. These are applied with the help of a brush or rod. After application volatile solvent evaporates leaving flexible, protective film covering the site.

4. Draughts: Draughts are liquid oral preparations of which only one or two rather large doses of the order of 50ml are prescribed. Each dose is issued in separate container.

5. Dusting Powders: These are powders which are in a fine state of subdivision, for external applications.

They are not to be applied to the broken skin. Dusting powders are sterile powders.

6. Ear Drops: These are solutions of drugs that are instilled into the ear with a dropper.

7. Elixirs: These are clear liquids oral preparations of potent or nauseous drug. They are pleasantly flavoured and usually attractively coloured.

8. Emulsions: These are biphasic dispersed liquid dosage forms, in which two immiscible liquids are mixed with the help of emulsifying agent.

9. Enemas: An emulsion is solutions suspensions or oil in water emulsion of medicaments intended for rectal use.

10. Gargles: It is aqueous solutions used to prevent or treat throat infections. Usually they are dispensed in concentrated forms with directions for dilution with warm water before use.

11. Effervescent Granules: These are the mixture of citric acid and tartaric acid with sodium-bi –carbonate.

One or more Organoleptic agents are used. After addition of granules in to water bicarbonate reacts with bicarbonates and produces carbonic acid and preparation is taken during effervescence and immediately afterward.

12. Inhalations: There are liquid preparations of or containing volatile substance.
These are used to relieve conjection and inflammation of the respiratory tract infections.

13. Insufflations: These are medicated ducting powders that are blown by insufflators into regions such as the nose, throat, body cavities and the ear to which it would be difficult to apply the powder directly.


14. Irrigations: These are solutions of medicaments used to treat infections of the bladder, vaginal and less often the nose. Thin soft rubber tubes used for irrigation solutions administration are Catheter. (Bladder) A vulcanite or plastic pipe (Vagina), Special Glass Irrigator (nose).

15. Jellies (Gels): Jellies are transparent or translucent nongreasy semi-solid preparations mainly used externally.

16. Linctuses: These are viscous liquids, oral preparations that are usually prescribed for the relief of cough. The dose in small and to ensure prolonged action, they should be sipped slowly and swallowed neat.

17. Liniments: These are fluid semi-solid or semi-fluid preparations intended for application to the skin. These are rubbed to affected area of skin for their counter irritant or stimulating effect but some are applied on a warm dressing or with a brush for analgesic and soothing effect. They should not be applied to broken skin.

18. Lotions: These are fluid preparations for external application without friction.

19. Lozenges (Troches): These are solid dosage forms consisting mainly of sugar and gum, the gum give hardness and cohesiveness and ensuring slow release of the medicaments. They are used to medicate the mouth and throat and for slow administration of the indigestion and cough remedies.

20. Mixtures: These are the most common form of liquid orals preparations usually with aqueous vehicle and the medicaments may be in solution or suspension.

21. Mouthwashes: These are similar to gargles but are used for oral hygiene and to treat infections of the mouth.

22. Nasal Drops: These are solutions of drugs that are instilled into the nose with a dropper. They are usually aqueous because oily drops inhibit movement of cilia in the nasal mucosa and long term use may cause Lipoidal Pneumonia.

23. Ointment: These are semi-solids, greasy preparations for external use to skin, rectum and nasal mucosa.

24. Paediatric Drops: Occasionally, the children’s dose of a preparation is very small and stability considerations preclude dilution to 5ml. Then the dose is prescribed as a fraction of ML and is given by a calibrated dropper.

25. Paints: These are liquids for application to the skin or mucosa usually with a soft brush. Skin paints often have a volatile solvent that evaporates quickly to leave a dry or resinous film of medicament.

Throat pains are more viscous due to high concentration of Glycerines.

26. Pastes: These are semi-solid preparation of external application that differs from similar products in containing high proportion of finely powdered medicaments. The base may be anhydrous or water soluble. Heir stiffness makes them useful as protective coating.

27. Pastilles: Pastilles are solid medicated preparations intended to dissolve slowly in the mouth. They are softer than lozenges and their basis is either glycerol or acacia and sugar.

28. Pills: Pills are oral dosage forms that have largely been replaced by tablets and capsules. They are spherical or less often ovoid and usually Sugar-Coated.

29. Poultices: These are paste like preparations used externally to reduce inflammation because they retain heat well. After heating, the preparation is spread thickly on a dressing and applied, as hot as the patient can bear it to the affected area.

30. Powders: Powders may be defined as the fine particles which are result of communation or granulation of the dry substance.

A powder can be mixture of drugs or chemicals which are uniformly mixed together and presented in dry form. Powders are intended for Internal and External usages.

31. Solutions: These are used for many purposes. For some of these sterility is necessary e.g. Parenteral, Peritoneal dialysis and Anticoagulant solutions, Bladder irrigations and Dermatological solutions for application to broken skin. Non sterile solutions are used orally and externally.

32. Solution Tablets: These are compressed tablets that are dissolved in water to produce solution for application to the skin or mucosa. They are formed to dissolve quickly.

33. Sprays: Sprays are preparations of drugs in aqueous, alcoholic or glycerine containing media. They are applied to the mucosa of nose or throat with an atomizer or nebuliser.

34. Syrups: These are aqueous concentrated, sucrose solutions with or without one or medicaments.

Organoleptic agents are added in syrups.

35. Vitrellae: Are thin walled glass capsule containing a volatile ingredients and protected by absorbent cotton wool and an outer silk bag. For use, in angina pectoris, these capsules are crushed and the Vapours are inhaled.

36. Extracts: These are concentrated preparations containing the active principles of vegetable or animal drugs. The drugs are extracted with suitable solvents and the product is concentrated to liquid or dry or soft mass extracts.

37. Glycerines: These are solutions of medicaments in glycerol with or without addition of water.

38. Infusions: Fresh infusions made by extracting drugs for a short time with cold or boiling water are no longer used because they quickly deteriorate as a result of microbial contamination and therefore must be used within 12 hours of preparation.

39. Oxymels: As the name suggests these are preparations in which the vehicle is a mixture of acid (Acetic) and Honey.

40. Spirits: Spirits are alcoholic or Hydro-alcoholic solutions of volatile substances. Most are used are flavouring agents but a few have medicinal values.



41. Tinctures: These are alcoholic preparations containing the active principles of vegetable drugs. They are relatively weak compared with extracts.

42. Aromatic waters: These are dilute usually saturated solutions of volatile oils or other volatile substances (Chloroform and Camphor, Menthol). They are mainly used as Flavouring agents and Carminatives.

Ayurvedic medicines

CLASSIFICATION AND DEFINITIONS:

Ayurvedic medicines are all the medicines intended for internal or external use, for or in the diagnosis treatment, mitigation or prevention of disease or disorder in human beings or animal and manufactured exclusively in accordance with the formulae described in the authorative books of Ayurvedic Systems of medicine specified in the first schedule of the Drug and Cosmetic act 1940. Ayurvedic Drugs are obtained from the natural source that is from animal, plants and minerals. Ayurvedic Dosages forms are classified in to four groups depending upon their physical forms:

a) Solid Dosage Forms: Pills, Gutika, Vatika.


b) Semi-solid Dosage Forms: Avleha, Paka, Lepa, Ghrta.

c) Liquid Dosage Forms: Asava, Arista, Arista, Arka, Taila, Dravaka.

d) Powder Dosage Forms: Bhasma, Satva, Mandura, Pisti, Parpati, Lavana, Kshara, Churna.
Pharmaceutical aids like Binding agent, Flavouring agent, Sweetning agents, Colouring agents, Preservatives are commonly used in Ayurvedic Formulae.

1) Asava and Arista:
Asava and Arista are the medicinal preparations prepared by soaking the drugs in the powdered forms or in the form of their decoction, in a solution of sugar or jaggery as may have intended for a specific period of time.

2) Arka:
It is the liquid preparation obtained by distillation of certain liquids or curde – drugs soaked in water using the distillation unit, (Arkayantra)

3) Avleha or Leha and Paka:
Avleha or Leha is a Semi-solid preparations of drugs prepared by addition of sugar, jaggery or sugar candy and boiled with prescribed drug juice or decoction.

4) Kvatha Curna:
The coarse powder of crude drugs or the combination of drugs in powder form, kept ready for preparation of decoction (Kasaya) are known as Kvath Curna.
e.g.: Dasmula Kvath Curna, Rasanadi Kvath Curna.


5) Curna (Churna):
Fine powder of drug or drugs is known as Curna, Drugs mentioned in yoga are cleaned, properly, dried thoroughly, Pulversied and then sieved.

6) Dravaka:
The liquid preparations obtained from lavanas or ksharas are known as Dravakas. They are prepared by distillation process with or without addition of any fluids.
e.g.: Sankha Dravaka.

7) Ksaras:
Alakaline substances obtained from the ash of drugs are known as Ksaras. Drugs are cut in to small pieces and burnt to get ash. Ash is dissolved in water, stained again evaporated to get rid of water while salty solid obtained is known as Ksar.
e.g.: Yav Ksara, Palsa Ksara.

8) Lepa:
The preparations in the form of paste meant for external applications on the body are known as Lepa.
e.g.: Sinduradi Lepa, Pathyadi Lepa.

9) Vati or Gutika:
Medicaments in the form of Tablets or pills are known as vati or Gutika.
e.g.: Muktadi Mahanjana and Chandroday Vartti.

10) Netrabindu and Anjan
Netrabindu is made by dissolving the specified drugs in water or kasaya or honey and used as eye drops. Anjans are very fine powders of medicaments to be applied with netrasalaka.
e.g.: Muktadi Mahanjana and Chandroday Vartti.

11) Sattva:
Water extractable solid substances obtained from drugs are known as Sattva.
e.g.: Gulvel Sattva.

12) Pisti:
These are obtained by triturating the drug with the specified liquids and exposing to sun or moon light.
e.g.: Praval Pisti, Mukta Pisti.

13) Ghrta (Snehkalapa):
These are preparations in which ghee in boiled with the prescribed quantity of the decoction and fine paste of the drug as specified in the formula.

14) Taila (Oils):
Tailas are the preparations in which tailas (Fixed Oils) is boiled with specified becoction and fine paste of the drug as mentioned in the prescribed formula.
e.g.: Bhrangaraja Taila, Maha Narayan Taila.


15) Bhasma:
The powdered form of the substances, obtained by calcination of metals minerals or animal products by a special process in closed crucibles in pits covered with cow dung cake (Puta) is known as Bhasma.
e.g.: Godanti Bhasma, Lauha Bhasma.

16) Rasa-Yoga:
The Medicinal Preparations containing mineral drugs as their main ingredients in the form of powder or pills are known as Rasa Yoga.
e.g.: Kapura Rasa, Laghu Malini Vasant Rasa.

17) Kupipakva-Rasayana:
These are the drugs prepared as: The minerals and drugs of metallic origin in the powdered form are mixed together and placed in glass flask occupying about one third of volume. The glass flask is closed with clay smeared pieces of cloth around the bottle in seven consecutive layers. The flask is dried and buried in sand (Valukayantra) up to neck. The flask in Valukayantra is then heated gradually in three that is Mrdu-agni, Madyamgni and tiksnagni for specified period of time as mentioned in process. Then the red hot iron rod about 5cm in diameter is inserted in glass flask through the opening and stirred properly, do that opening of flask is not chocked due to the coating formed by sublimed Sulphur. When the process is over, the glass flask is cooled and broken to collect the content carefully without the contamination of any glass pieces therein.
e.g.: Makaradhvaja, Swarna sindura.