DESIGN AND FORMULATION OF SUSTAINED RELEASE TABLETS

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DESIGN AND FORMULATION OF SUSTAINED RELEASE TABLETS : 

DESIGN AND FORMULATION OF SUSTAINED RELEASE TABLETS AJU S. SAM 1st yr. M.Pharm DEPARTMENT OF PHARMACEUTICS NEHRU COLLEGE OF PHARMACY

INTRODUCTION: : 

INTRODUCTION: Designed to achieve a prolonged therapeutic effect. Depends on residence time in GI tract. Design embodies the approach to control drug action. Drug modification. Dosage form modification.

ADVANTAGES: : 

ADVANTAGES: Reduced frequency of administration. Improved patient compliance. More even blood level maintained. Maximum availability with a minimum dose. Increased safety margin. Reduced ADR. Increased reliability of therapy.

DISADVANTAGES: : 

DISADVANTAGES: Does not permit prompt termination of therapy. Immediate change in drug therapy not accommodated. Less flexibility in adjusting dosage regimen. Economic factors.

DESIGN: : 

DESIGN:

Drug modification: : 

Drug modification:

DRUG COMPLEX : : 

DRUG COMPLEX : The effective release rate depends on Rate of dissolution. Rate of dissociation. Dissolution rate = Ks ˣ surface area Rate of dissolution > Rate of dissociation zero order release pattern occurs. Rate of dissociation > Rate of dissolution dissolution of complex is the rate determining step.

Cont.. : 

Cont.. D = diffusion coefficient Cs = solubility h = thickness of diffusion layer ῤ = density W = weight of undissolved solid

DRUG ADSORBATE : : 

DRUG ADSORBATE : Drug availability determined by Rate of dissociation (Desorption). Access of adsorbent surface to water. Effective surface area of adsorbate.

PRODRUGS : : 

PRODRUGS : The solubility, absorption rate and elimination rate constant should be lower than parent compound. Isoniazid , Penicillin, isoproterenol. Solubility reduced and break down takes place at absorption site then availability limited by dissolution rate.

Cont.. : 

Cont.. Preparation of drug dispersion through molecular scale drug entrapment. Suitable carrier materials act to retard release. Mechanism similar to drug adsorbates.

Dosage form modification: : 

Dosage form modification: Allows direct incorporation of loading dose.

Cont… : 

Cont… Principles involved in retarding drug release. Embedded matrix Drug dispersed in matrix Drug dissolved in matrix Barrier Diffusion of drug Permeation of barrier Erosion of barrier

Cont.. : 

Cont.. Higuchi’s equation defining drug release from inert matrices. Q = [(DɛCs/T)(2A – ɛCs) t ] ½ Q – amount of drug release/ unit surface after time t. D – diffusion coefficient of drug in elution medium T - tortuosity of matrix ɛ - porosity of matrix Cs – solubility of drug in elution medium A – initial loading dose of drug in matrix

Cont.. : 

Cont.. Barrier mediated models

Formulation: : 

Formulation: Drug complexes. Encapsulated slow release granules. Tabletted slow release granulations. Matrix tablets. Controlled release technology.

Drug complexes : : 

Drug complexes : Complex acids – poly galacturonic acid, arabogalactone sulphate. Bentonite + amine salts, cationic / nonionic drugs. Ion exchange resin complexes. Styrene/ divinyl benzene copolymer resins.

Encapsulated slow release granules : : 

Encapsulated slow release granules : Pseudo latexes of ethyl cellulose modified by dibutyl sebacate & plasticized by triethyl citrate. Coating with hydrolyzed styrene maleic acid copolymer. PEG modified ethyl cellulose. Shellac, cellulose acetate phthalate. Hydrogenated oils, glyceryl stearates, fatty alcohols, microcrystalline wax. 2-10% wicking agents; greater uniform drug release

Tabletted slow release granules : : 

Tabletted slow release granules : Tabletted mixed release granulation. Based on microdialysis cell principle. Matrix of loading dose & maintenance dose encapsulated in semi permeable coating.

Matrix tablets : : 

Matrix tablets : Drug embedded in matrix core of retardant.

Cont.. : 

Cont.. Loading dose are included as second layer of a two layer tablet or in a coating applied to the matrix core. Insoluble , inert - rate limiting step is liquid penetration into matrix. If wetting agent present – pore diffusion. Retardant base – carnauba wax with stearic acid or stearyl alcohol.

Cont.. : 

Cont..

Cont... : 

Cont... Hydrophilic – forms gel in situ. Release controlled by penetration of water and diffusion of drug through hydrated matrix. Best matrix former – HMC 90 HG 15000,cps

CONTROLLED RELEASE TECHNOLOGY : : 

CONTROLLED RELEASE TECHNOLOGY : CONTROLLED RELEASE SYSTEMS Dissolution controlled Diffusion & Dissolution controlled Diffusion controlled Ion-exchange resins Hydrogels Chemically controlled Water penetration controlled

REFERENCES: : 

REFERENCES: Leon Lachman, Herbert A. Lieberman. The Theory and Practice of Industrial Pharmacy, special Indian edition; 2009: 430 – 456. Lieberman, Lachman, Schwartz. Pharmaceutical Dosage Forms: Tablets, volume III, second edition: 188- 212.

Slide 26: 

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