Original Article

THE EFFECTS OF POLYMER TYPE AND RATIO ON THE EXTENDED RELEASE OF ATENOLOL FROM HYDROPHILIC MATRICES

  • Evren ALGIN
  • Özge INAL
  • Tamer BAYKARA

Received Date: 18.07.2006 Accepted Date: 15.12.2006 Turk J Pharm Sci 2007;4(1):41-52

Abstract In this study, the effects of type and ratio of the polymers [hydroxypropylmethylcellulose (Methocel® K100LV and K15M), methacrylic acid copolymer (Eudragit® L100)] and direct compression agents (Pharmatose DCL11®, Cellactose® 80, Microcel® PH101) on the extended release of atenolol from hydrophilic matrix tablets prepared by direct compression method were investigated. Spectrophotometric method used for the determination of atenolol in dissolution media was validated by calculating linearity and range, precision, accuracy and specificity values. The dissolution profiles showed that hydroxypropylmethylcellulose ratio and type play a significant role in drug release and direct compression agents (lactose or cellulose based) can be effective on drug release at the presence of low amounts of hydroxypropylmethylcellulose in the formulations. It is also observed that methacrylic acid copolymer could not effectively hinder the drug release in acidic medium and binary mixtures of polymers could lead to discontinuous drug release profiles. Results indicated that low viscosity grade hydroxypropylmethylcellulose can be preferred to obtain linear drug release profiles for a duration of eight hours with a lactose-based direct compression agent. Results of kinetic data indicated that atenolol release from the formulations generally fits best to the Korsmeyer-Peppas kinetic model and drug release mechanism shows non-Fickian transport mechanism according to the values of diffusion exponent. Özet Bu çalismada polimerler [hidroksipropilmetilselüloz (Methocel® K100LV ve K15M), metakrilik asit kopolimeri (Eudragit® L100)] ve dogrudan tabletleme ajanlarinin (Pharmatose DCL11®, Cellactose® 80, Microcel® PH101) tip ve oranlarinin atenolol’ün dogrudan basim yöntemi ile hazirlanan hidrofilik matris tabletlerinden uzatilmis salimi üzerindeki etkileri incelenmistir. Atenolol’ün çözünme ortamlarindaki tayininde kullanilan spektrofotometrik analiz yöntemin validasyonu için, dogrusallik ve araligi, kesinlik, dogruluk ve seçicilik degerleri hesaplanmistir. Çözünme hizi profilleri, etkin madde salimi üzerinde hidroksipropilmetilselüloz orani ve tipinin önemli rol oynadigini ve dogrudan tabletleme ajanlarinin (laktoz veya selüloz kökenli) formülasyonlarda hidroksipropilmetilselüloz oraninin düsük olmasi durumunda etkili olabilecegini göstermektedir. Metakrilik asit kopolimerinin asit ortamda etkin madde salimini etkili bir biçimde baskilayamadigi ve ikili polimer karisimlarinin düzensiz etkin madde salim profillerine neden olabilecegi de görülmektedir. Sonuçlar, düsük viskoziteli hidroksipropilmetilselülozun laktoz kökenli bir dogrudan tabletleme ajani ile beraber, sekiz saatlik sürede dogrusal etkin madde salim profili elde etmek amaciyla tercih edilebilecegini göstermektedir. Kinetik veriler, formülasyonlardan atenolol saliminin genellikle en iyi Korsmeyer-Peppas kinetik modeline uydugunu ve difüzyon katsayisi degerlerine göre etkin madde salim mekanizmasinin Fick’e uymayan tasinma durumuna uydugunu belirtmektedir.

Keywords: Atenolol, HPMC, methacrylates, matrix tablet, direct compression, release kinetics