Optimasi formula tablet lepas lambat nifedipin dengan sistem matrik hidroksi propil metil selulosa, etil selulosa, dan laktosa

NURJAYANTI, Ida, Prof. Dr. Sri Sulihtyowati Soebagyo, Apt

2008 | Tesis | S2 Ilmu Farmasi

Nifedipin mempunyai kelarutan rendah dalam air dan memiliki t1/2 yang relatif pendek (2-5 jam). Beberapa eksipien seperti polivinil pirolidon dan polietilen glikol diketahui dapat meningkatkan kelarutan obat dalam air. Tablet sistem matrik dapat mengontrol pelepasan obat melalui proses difusi-erosi. Tujuan penelitian ini adalah: 1. Mengetahui pengaruh jumlah PVP K-30 dan PEG 4000 serta interaksinya terhadap kelarutan nifedipin, 2. Mengetahui pengaruh jumlah HPMC (X1), etil selulosa (X2), dan laktosa (X3) serta interaksinya terhadap sifat fisik massa tablet dan kecepatan pelepasan nifedipin, dan 3. Menentukan formula optimum tablet lepas lambat nifedipin yang dibuat dengan metode granulasi kering. Penelitian ini memakai metode simplex lattice design (SLD). Parameter sifat fisik massa tablet yang diamati adalah kecepatan alir (g/det) dan kompaktibilitas (kg); dan parameter untuk tablet yaitu homogenitas (% CV), kecepatan pelepasan dan koefisien korelasi kinetika orde nol. Formula optimum ditentukan dari persamaan dan superimposed contour plot. Berdasarkan penelitian diketahui bahwa PVP K-30 merupakan solubilizer yang lebih baik dibanding PEG 4000. Oleh karena itu, campuran nifedipin dan PVP K-30. 1:2 digunakan sebagai solubilizer. Makin besar jumlah etil selulosa secara signifikan meningkatkan kecepatan alir, homogenitas, kompaktibilitas, dan koefisien korelasi orde nol serta menurunkan kecepatan pelepasan. Hal ini berkebalikan apabila kadar HPMC makin besar. Semakin besar kadar laktosa secara signifikan meningkatkan kecepatan alir, homogenitas, kompaktibilitas, dan kecepatan pelepasan serta menurunkan koefisien korelasi orde nol. Berdasarkan superimposed contour plot, diperoleh formula optimum yang terdiri HPMC 0,06-0,34 (5,4-30,6 mg), etil selulosa 0,53-0,86 (47,7-77,4 mg) dan laktosa 0,06-0,17 (5,4-15,3 mg); formula tersebut mempunyai kecepatan alir lebih besar dari 10 g/det, kompaktibilitas 6-8 kg, % CV homogenitas kurang dari 5,0%, kecepatan pelepasan 0,022-0,030 mg/min dan koefisien korelasi lebih besar dari 0,90.

Nifedipine has a low solubility in water with a relatively short elimination half-life (2-5 hr). Some excipients, i.e. polyvinyl pyrolidone and polyetilen glycol are reported to increase the solubility of drug in water. Matrix system of tablet can control drug release by diffusion-erosion system. Therefore, the aim of this study were: 1. To investigate the influence of the PVP K-30 and PEG 4000 concentration and their interaction on solubility of nifedipine, 2. To investigate the effect of the ethyl cellulose (X1), HPMC (X2), and lactose (X3) concentration and their interaction on the physical properties of the tablet mass and the release rate of nifedipine, and 3. To determine the optimum formula of nifedipine sustained-release tablet, produced by dry granulation method. Simplex lattice design (SLD) has been implemented in the study. The physical property parameters of tablet mass were flowability (g/sec) and compactibility (kg); for the physical property parameters of tablet were homogeneity (CV,%), the released rate constant and the correlation coefficient of zero order kinetics. Optimum formula was determined based on optimization equation and superimposed contour plots. PVP K-30 was a better solubilizer than PEG 4000. Therefore, the mixture of nifedipine and PVP K-30, 1:2 was used as solubilizer. Increase of ethyl cellulose amount significantly increased the flowability, homogeneity, compactibility, zero order coefficient correlation, and decreased release rate constant. This is contrast while HPMC is increased. Increase in lactose amount significantly increased the flowability, homogeneity, compactibility, release rate constant, and decreased the zero order coefficient correlation. Based on superimposed contour plot, tablet formula consisting of HPMC 0.06-0.34 (5.4-30.6 mg), ethyl cellulose 0.53-0.86 (47.7-77.4 mg) and lactose 0.06-0.17 (5.4-15.3 mg) was chosen as the optimum formula and has flowability of more than 10 g/sec, a compactibility of 6-8 kg, CV homogeneity of less than 5.0%, zero order release rate constant 0.022-0.030 mg/min and correlation coefficient of more than 0.90.

Kata Kunci : Nifedipin,Solubilizer,Matrik,Channelling agent,Lepas lambat,Simplex lattice design, nifedipine, solubilizer, matrix, channelling agent, sustained-released, simplex lattice design