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.