Müge KILIÇARSLAN, Evren ALĞIN, Nilüfer YÜKSEL, Tamer BAYKARA, Ayşegül KARATAŞ

Effects of polymer type, polymer: Direct tabletting agent ratio and tabletting method on verapamil hydrochloride extended release from hydroxypropylmethylcellulose matrix tablets

Bu çalışma farklı hidroksipropilmetilselüloz (HPMC) tiplerinin ve HPMCdoğrudan tabletleme ajanı (dta) oranının, tek tabakalı ve üç tabakalı matris tabletlerden Verapamil Hidroklorür^ün (VRP HCl) salımı üzerindeki etkilerine odaklanmıştır. İncelenen polimerler Methocel K100LV, K15M, K100M ve dta Ludipress® LCE'dir. Sekiz adet tek tabakalı ve dört adet üç tabakalı matris tablet doğrudan basım yöntemi kullanılarak hazırlanmıştır. Etkin madde salım çalışmaları USP XXVH'de yer alan uzatılmış salım yapan ilaç şekillerine ait makaleler prosedürüne uygun olarak yapılmıştır. HPMC tipi ve oranının etkin madde salımı üzerine etkili olduğu saptanmıştır. HPMC miktarı ve viskozluğundaki artışın, matrislerden etkin madde şahmının yavaşlamasına neden olduğu tespit edilmiştir. İç ve dış tabakalarda düşük viskozluğa sahip HPMC içeren tabletler, farmakope limitlerine yakın veya limitler içinde salım profilleri vermişlerdir. USP XXVII kriterlerine uyan üç tabakalı matris tablet (Fi 2) ve referans ürüne (Isoptin®-KKH) ait salım verileri matematiksel modeller (sıfır derece, birinci derece, Higuchi, Hixson-Crowell, Korsmeyer-Peppas), fark faktörü (f,) ve benzerlik faktörü (fz) kullanılarak değerlendirilmiştir. VRP HCVin salım kinetikleri F12 için en iyi Higuchi modeline, Isoptin®-KKH için sıfır derece kinetik modeline uyum göstermiştir. Fİ 2 ve Isoptin®-KKH*ın her ikisi de n katsayılarına göre Anomali durumu göstermiştir, f (5.2) ve f2 ( 71.4) değerlerine göre Fİ2 ile Isoptin®-KKH benzer kabul edilmiştir.

Polimer tipinin, polimer: Doğrudan tabletleme ajanı oranının ve tabletleme yönteminin hidroksipropilmetilselüloz yapılı matris tabletlerden verapamil hidroklorür'ün uzatılmış salımı üzerine etkileri

This work has focused on the effects of different hydroxypropylmethylcellulose (HPMC) types and HPMC.direct tabletting agent (DC-agent) ratio on Verapamil Hydrochloride (VRP HCl) release from monolayered and three-layered matrix tablets. Investigated polymers were Methocel K100LV, K15M, K100M and DC-agent was Ludipress® LCE. Eight formulations were prepared as monolayered matrix tablets while four formulations were prepared as three-layered matrix tablets by direct compression method. Drug release studies were carried out according to the method given for Delayed Release Articles in USP XXVII. HPMC types and ratios were found to be effective on drug release. Increasing amount and viscosity grade of HPMC resulted in a decrease in release of drug from the matrices. Tablets containing low viscosity grade HPMC at inner and outer layers presented release profiles close to or within the limits of pharmacopeia. Release data of three-layered matrix tablet (F12) and the reference product (Isoptin -KKH) which were in agreement with USP XXVII criteria, were evaluated by mathematical models (zero order, first order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas), difference factor (fi) and similarity factor (fi).. The kinetics of VRP HCl release from FI2 showed best fit to Higuchi model and Isoptinm-KKH well fitted to zero order kinetic model. FI2 and Isoptin -KKH were both show Anomalous transport mechanism 'according tn thcir n exponent values. Depending on the results off] (5.2) and J2 (71.4) values, F12 and lsuplinK-KKIl were found to be similar with regard to release kinetics.

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