This document discusses characterization of raw materials in pharmaceutical development. It describes various techniques used to characterize active pharmaceutical ingredients (APIs) and excipients including physical characterization of bulk properties, solid state properties and intrinsic properties. It also discusses chemical characterization techniques like nuclear magnetic resonance spectroscopy, mass spectroscopy and elemental analysis to confirm the API structure. Additional techniques described are solubility analysis, dissolution testing, solid state properties analysis and stability analysis of APIs, excipients and their mixtures.

1. PRESENTED BY
HIBA.C.H
RESHMA FATHIMA.K
FIRST YEAR M.PHARM
DEPT.OF.PHARMACEUTICS
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2. CHARACTERIZATION OF RAW MATERIALS
 PHYSICAL CHARACTERIZATION
Bulk properties of API
Solid state properties of API
Intrinsic properties of API
 CHEMICAL CHARACTERIZATION
Confirmation of structure of API
Stability Analysis
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Confirmation of
structure of API
Stability/compatibility studies on
API/excipient mix ,Solubility
Dissolution
Changes on processing
Particlehabit/shape,
Particlesize/distribution
Density,Surface area,Flowability
Compaction
Polymorphism,Solvation,Crystallinity
Solubility,Partitioning/distribution
Melting/boiling points/sublimation
Dissolution
Nuclear magnetic resonance (NMR)
Mass spectroscopy,Elemental
analysis
API/excipient mix
Bulk properties of
API
Solid state
properties of API
Fundamental/intrinsic
properties of API

4. CONFIRMATION OF STRUCTURE OF API
 NMR SPECTROSCOPY
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5.  IR SPECTROSCOPY
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6. MASS SPECTROSCOPY
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7. INTRINSIC PROPERTIES OF API
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8. SOLUBILTY ANALYSIS INCLUDE
 Pka determination
 pH solubility profile
 Common ion effects
 Effect of temperature
 Solubilization
 Partition coefficient
 dissolution
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9. Pka determinations
 Henderson hasselbalch equation
 Unionised drug absorbed from the GIT tract
 Pka value can be determined by variety of analytical methods.
 Spectral shifts by UV or visible spectroscopy
 Potentiometric titrations
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10. Common ion effects
 common ion effect is defined as the suppression of the degree of
dissociation of a weak electrolyte containing a common ion.
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11. Effect of temperature
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12. DISSOLUTION
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Dissolution is the process by which a solute forms
a solution in a solvent. The solute, in the case of solids, has
its crystalline structure disintegrated as separate ions,
atoms, and molecules form

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14. PARTITION COEFFICIENT
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15. MELTING POINT
 CAPILLARY MELTING
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16.  HOT STAGE MICROSCOPY
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17. SOLID STATE PROPERTIES
 POLYMORPHISM
 CRYSTALLINITY
 SOLVATION
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18. DIFFERENTIAL SCANNING CALORIMETRY
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19. DIFFERENTIAL THERMAL ANALYSIS
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20. BULK PROPERTIES OF API
PARTICLE SIZE
PARTICLE SHAPE
SURFACE AREA
DENSITY
FLOW PROPERTIES
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21. STABILITY ANALYSIS
 SOLUTION STABILITY
 SOLID STATE STABIULITY
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22. STABILITYIN TOXICOLOGYFORMULATION
 Toxicology studies typically commence early in
development, it is often advisable to evaluate samples of
the toxicology preparation for stability and potential
homogeneity problems.
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23. Solutionstability
The primary objective of this phase of pre-formulation research is
identification of condition necessary to form a stable solution.
This study include-effect of pH, ionic strength, light, temperature and oxygen
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24. Solidstate stability
 Solid phase stability depends on several factors like temperature, pH, humidity,
hydrolysis, oxidation, etc
 For a new drug compound
Weighed sample are place in open screw cap vials and are exposed directly to light, temp,
humidity for 12weeks.
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25. INCOMPATIBILITY
ADAVANTAGE
 It helps to avoid surprise problems
TYPES
 Physical incompactibility
 Chemical incompactibility
 Therapeutic incompactibility
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26. Excipient interaction
 Drug –Excipient interactions
 Physical interaction
 chemical interaction
 Biopharmaceutical interaction
 Excipient –Excipient interactions
 Package –Excipient interaction
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27. PHYSICAL INTERACTION
 Tetracycline formed insoluble complex with calcium carbonate leading to
slower dissolution and decreased absorption.
 Formulation of chlorpromazine with polysorbate 80 and sodium lauryl
sulphate decreased membrane permeability of drug.
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28. CHEMICAL INTERACTION
 Antibiotics, anaesthetics,barbiturates undergo in presence of water low or
high pH.
 Steroids, Vitamins, Antibiotics, Epinephrine, Aldehydes, Alcohols,
Phenols undergo oxidation reactions
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29. BIOPHARMACEUTICAL INTERACTIONS
 Many of the excipients like sorbital, xylitol, have tendency to increase the
gastrointestinal motility thus reducing the time available for absorption of
drugs like metoprolol.
 Polyethylene glycol 400 also has influence on the absorption of ranitidine
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30. EXCIPIENT-EXCIPIENT INTERACTIONS
 Acacia -Ethanol (95%) - Precipitate organic salts of Acacia
 Acacia- Ferric and other salts-Mucilage of acacia becomes gelatinous.
 Crosscarmellose Sodium- Hygroscopic excipients like Sorbitol Efficacy as
disintegrant reduced.
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31. PACKAGE-EXCEPIENT INTERACTION
 Glass- Glass containers possess oxides of Boron, Sodium, Potassium,
Calcium, Iron and Magnesium which interact with formulation.
Alter physical and chemical stability of the formulation. E.g.:- sulphate salts
react with barium and calcium to form inorganic insoluble
salts.
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32.  Plastic- Moisture uptake
Moisture uptake associated with disintegrants(STARCH) in tablet form
microcracks due to disintegrant swelling.
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