Design and evaluation of sustained-release matrix once daily formulation of stavudine
Keywords:
Sustained release, Matrix tablets, Hydroxy propyl methylcellulose, StavudineAbstract
The aim of the present study was to formulate once daily sustained release matrix tablets of Stavudine to increase therapeutic efficacy, reduce frequency of administration and improve patient compliance. The sustained release tablets were prepared by direct compression and formulated using different drug: polymer ratios, formulations such as F1to F15. Hydrophilic polymers like Hydroxy propyl methyl cellulose (HPMC), Carboxymethyl cellulose (CMC) and Starch 1500 were used. Compatibility of the drug with various excipients was studied. The compressed tablets were evaluated and showed compliance with pharmacopoeial standards. Formulation containing Stavudine:HPMCK15: Na-CMC (1:2:0.5) with hardness 10-11kg/cm2 showed the desired release profile which matched the theoretical release profile. SEM studies of the formulations were carried out for the confirmation of mechanism of drug release. The in vitro drug release characteristics were studied in both simulated gastric and intestinal fluids for a period of 24 hr using USP Type 2 dissolution apparatus. Mathematical analysis of the release kinetics indicated a coupling of diffusion and erosion mechanisms. The study proves that the developed sustained release tablet is capable of releasing the drug in a sustained manner for 24 hr.
References
Agoram B, B.W.S. Woltosz, MB. Bolger.
Predicting the impact of physiological and
biochemical processes on oral drug bioavailability,
Adv Drug. Deliver. Rev2001;50: 41-67.
Lea AP, Fauld D. Stavudine: A review of its
pharmacodynamics and pharmacokinetics
properties and chemical potential in HIV infection.
Drugs 1996;51:854-864.
Huang P, Farquhar D, Plunkett W. Selective action
of 2’,3’- didehydro-2’,3’-dideoxythymidine
triphosphate on human immuno deficiency virus
reverse transcriptase and human DNA polymerases.
J. Biol. Chem 1982;267:1817-1822.
Pather S, Russel I, Syce J, Neau S. Sustained
release theophylline tablets by direct compression,
part-1: formulation and in vitro testing. Int. J.
Pharm1998;164: 1-10.
Salsa T, Veiga F, Pina ME. Oral controlled-release
dosage form. I. Cellulose ether polymers in
hydrophilic matrices. Drug Dev. Ind. Pharm1997;
: 929-938.
Cooper J, Gunn C. Powder flow and compaction.
In: Carter SJ, eds. Tutorial Pharmacy. New Delhi,
India: CBS Publishers and Distributors: 1986.p211-
Indian Pharmacopoeia. New Delhi: Controller of
Publications; 1996. p 735-36.
Rana, KZ., Dudley. MN. Clinical pharmacokinetics
of Stavudine. Drugs 1997;33:276-84.
Bristol- Myers Squibb Zerit XR package
insert.2002
Gilbert S. Banker., Neil R. Anderson. In: Leon
Lachman, Herbert A. Liberman, Joseph L. Kanig,
(Eds.). The Theory and Practice Of Industrial
Pharmacy, 3rd edn. Mumbai: Varghese Publishing
House: 1987.p293-373.
Velasco, M. V., Ford, J. L., Rowe, P., RajabiSiahboomi, A. R., . Influence of compression force
on the release of diclofenac sodium from HPMC
tablets. J. Contr. Rel1999;57: 75-85.
Rekhi, G. S., Nellore, R. V., Hussain, A. S.,
Tillman, L. G., Augsburger, L. L. Identification of
critical formulation and processing variables for
metoprolol tartrate extended-release (ER) matrix
tablets. J. Contr. Rel1999;59:327-342.
Mutalik S, Hiremath D. Formulation and evaluation
of chitosan matrix tablets of nifedipine. The Eastern
Pharmacist2000; 2:109-111.
Levina, M., Taylor, J, Siaboomi, A.R., “The
Influence of Starch 1500® on Drug Release from
HPMC Matrices,” Contributed paper, AAPS
National Meeting, October 2001.
Baveja, S.K., Hassan, A.U., Singh, A. Zero-order
release of pseudoephedrine hydrochloride from
hydrophilic matrix tablets. Ind. J. Pharm.
Sc1989;51: 248-51.
Korsmeyer RW, Gurny R, Peppas NA.
Mechanisms of solute release from porous
hydrophilic polymers. Int J Pharm1983;15:25-35.
Fassihi RA, Ritschel WA. Multiple layer, direct
compression controlled release system: In vitro and
in vivo evaluation. J Pharm Sci. 1993;82:750-754.
