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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  2. Chromatographic technique  3. melting point

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.

PHYSICOCHEMICAL PARAMETER AFFECT ABSORPTIN


Partition Coefficient  Ionization constant  Permeation across biological membrane  Dissolution rate and solubility  Particle size and effective surface area


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

rate & solubility across biological

 Permeation

membrane
 Particle

size and surface area

COMPATIBILITY WITH EXCIPIENT


Incompatibility:Incompatibility: It is a result of prescribing or mixing of substance which are formed undesirable product . There are two type 1. physical 2. chemical


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:

METHOD FOR COMPATIBILITY DETECTION


Chromatographic tech.  Thermal analysis  Diffuse reflectance spectroscopy
 

Conclusion:Conclusion:- Preformulation studies have significant role in anticipating formulation problem.

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

DRUG DEGRADATION MECHANISM


 Hydrolysis  Solvolysis  Oxidation  Photolysis  Metal

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 CHELATION & ISOMERISATION




 

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:-


 

1. Solid state stability


Tablet & capsule Free moisture ( 2% req. for compression)




2. Liquid state stability

Selection of granulation solvent Study when exposed to G.I.fluid (erythromycin)

Factor affecting solid dosage form stability


   

 

Moisture Excipient:Excipient:starch & povidone more water content Suppository base cause degradation of aspirin Temperature ( polymorphism) Light & oxygen

Factor affecting liquid dosage form stability


    

: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

  

Biopharmaceutics by brahmankar Physical pharmacy by martin

THANK YOU !

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