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PREFORMULATION STUDIES CHEMICAL PROPERTIES PRESENTED BY M.V.N Vishnu Teja, Mounika.K Teja, (MRIPS)
CONTENT
Introduction Objective Purity Physicochemical parameter affect absorption Solid phase stability Liquid phase stability Compatibility with excipient
INTRODUCTION
PREFORMULATION:PREFORMULATION:It can be defined as an investigation of physical and chemical properties of new drug substance alone or in combination with other excipient. Preformulation is also phase of research & development process where research scientist characterize physical, chemical and mechanical aspect of new drug under investigation in order to developed stable safe & effective dosage form
OBJECTIVE
To formulate stable and effective dosage form To increased drug stability To improve drug bioavailability Reduce drug excipient incompatibility
PURITY
Raw
material. Impurity affect drug stability Impurity also toxic affect appearance
DETECTION OF IMPURITY
Three
technique used
1.
THERMAL ANALYSIS
Definition:Definition:A group of tech. in which a physical property of a substance & its reaction product is measured as a function of temperature whilst the substance is subjected to a controlled temp. program. DTA DSC
CHROMATOGRAPHIC TECH.
Preparation of stationary phase & mobile phase Mobile phase run in both sample & standard substance Spot was developed Scraping the spot using a fine spatula Study the absorbance & compared it
MELTING POINT
Melting point:point:Defined as the temperature at which the solid and liquid phases are in equilibrium. Hot stage microscopy.
PARTION COEFFICIENT
It ratio of unionised drug in organic & aq. Phase P= C OIL/CWATER It measure lipophilicity Major role in drug transport Analytical separation
IONISATION CONSTANT
Many drug are weakly acidic and basic nature Unionised drug permeation of membrane. Ionization study by using condoctometry
Dissolution
Permeation
membrane
Particle
PHYSICAL INCOMPATIBILITY
Mixing a two substance affect it physical property like solubility, appearance, miscibility. Example:Example:oil water immiscible mixture Corrected:Corrected:- change solvent, mixing order.
CHEMICAL INCOMPATIBILY
Chemical reaction Reduction, oxidation, hydrolysis, These reaction notice by effervesce, ppt. formation colour change Example: quinine hydrochloride sodium salicylate water, in diffusible in nature Corrected:Corrected:
STABILITY STUDY
The purpose of stability testing to asses the effect of temp., humidity, light & environmental factor on quality of product Above data used for prediction of shelf life Potency should not loss under recommended storage condition Prediction of storage condition
chelating
HYDROLYSIS
Water play a major role Nucleophilic attack of water on labile group Drugs containing ester, amide, lactam, imide or carbamate groups are susceptible to hydrolysis. Hydrolysis can be catalysed by hydrogen ions (specifi c acid catalysis) or hydroxyl ions (specifi c base catalysis). Ex:Ex:- Penicillin
OXIDATION
Oxidation involves the removal of an electropositive atom, radical or electron, or the addition of an electronegative atom or radical. Oxidative degradation can occur by autooxidation, and proceeds quite slowly under the infl uence of molecular oxygen, Antioxidant act by provide electron, accept by free radical & terminate reaction Ex:Ex:- Steroid, simavastatin
PHOTOLYSIS
Exposed to radiation absorb light & decom. Photodecomposition may occur not only during storage, but also during use of the product. ( in case topical drug) product can be protect from photolysis by storage in amber colored bottle & dark place Tablet is protected by coating with polymer contain UV light absorbing substance Ex:Ex:- prednisolone riboflavine
Metal chelating agent form complex with drug ( EDTA, Ethylene diamine) diamine) Ex:Ex:- Ciprofloxacin Isomerisation is the process of conversion of a drug into its optical or geometric isomers, which are often of lower therapeutic activity Ex:Ex:-Adrenaline (epinephrine ) tetracycline
STABILITY TYPE
TWO TYPE:TYPE:-
Moisture Excipient:Excipient:starch & povidone more water content Suppository base cause degradation of aspirin Temperature ( polymorphism) Light & oxygen
:PH :catalytic effect of H+, & OH- ions . Hydrolysis in solution Temperature:Temperature:- arrhenius equ. Solvent effect:effect:-
This method based on raising the temperature log k = log A Ea/2.303RT Plot of k vs. 1|T
ARRHENIUS EQUTION
K 1|T Studies on elevated temp.& estimate K at room temp.by extrapolating line. No change after 30 day at. 600 c stability excell
Reference
pharmaceutics the science of dosage from design by, Aulten M.E. The theory and practice of Industrial Pharmacy. By Leon lachman,Herbert A. Liberman, Josep K. kanig 3rd Edition. Pharmaceutical dosage fomrs, volume-I by volumeherbert. Lieberman, leon lachaman. Instrumental spectsroscopy by Skoog 5th
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