PRESENTED BY

HIBA.C.H

RESHMA FATHIMA.K

FIRST YEAR M.PHARM

DEPT.OF.PHARMACEUTICS

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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 ,SolubilityDissolutionChanges on processing

Particlehabit/shape,Particlesize/distributionDensity,Surface area,FlowabilityCompaction

Polymorphism,Solvation,Crystallinity

Solubility,Partitioning/distributionMelting/boiling points/sublimationDissolution

Nuclear magnetic resonance (NMR)Mass spectroscopy,Elementalanalysis

API/excipient mix

Bulk properties of

API

Solid state

properties of API

Fundamental/intrinsic

properties of API

CONFIRMATION OF STRUCTURE OF API

NMR SPECTROSCOPY

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IR SPECTROSCOPY

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MASS SPECTROSCOPY

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INTRINSIC PROPERTIES OF API

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SOLUBILTY ANALYSIS INCLUDE Pka determination

pH solubility profile

Common ion effects

Effect of temperature

Solubilization

Partition coefficient

dissolution

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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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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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Effect of temperature

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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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PARTITION COEFFICIENT

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MELTING POINT CAPILLARY MELTING

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HOT STAGE MICROSCOPY

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SOLID STATE PROPERTIES POLYMORPHISM

CRYSTALLINITY

SOLVATION

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DIFFERENTIAL SCANNING CALORIMETRY

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DIFFERENTIAL THERMAL ANALYSIS

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BULK PROPERTIES OF APIPARTICLE SIZE

PARTICLE SHAPE

SURFACE AREA

DENSITY

FLOW PROPERTIES

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STABILITY ANALYSIS

SOLUTION STABILITY

SOLID STATE STABIULITY

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STABILITY IN TOXICOLOGY FORMULATION

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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Solution stabilityThe 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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Solid state 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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INCOMPATIBILITYADAVANTAGE

It helps to avoid surprise problems

TYPES

Physical incompactibility

Chemical incompactibility

Therapeutic incompactibility

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Excipient interaction

Drug –Excipient interactions

Physical interaction

chemical interaction

Biopharmaceutical interaction

Excipient –Excipient interactions

Package –Excipient interaction

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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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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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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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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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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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Plastic- Moisture uptake

Moisture uptake associated with disintegrants(STARCH) in tablet form microcracks due to disintegrant swelling.

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