Pengaruh kadar dan interaksi Etil Selulosa, Tablettose dan Magnesium Stearat terhadap sifat fisik Massa Tablet dan pelepasan Propranolol HCl dari tablet sistem Matriks

KUSWAHYUNING, Rina, Prof.Dr. Sri Sulihtyowati Soebagyo, Apt

2005 | Tesis | S2 Ilmu Farmasi

Sistem matriks tablet dapat mengontrol kecepatan pelepasan obat secara erosi-difusi berdasarkan kombinasi bahan pembentuk matriks (etil selulosa), channelling agent (tablettose) dan lubrikan yang bersifat hidrofob (magnesium stearat). Kualitas tablet antara lain dipengaruhi oleh sifat fisik massa tabletnya. Oleh karena itu, penelitian ini bertujuan untuk mengetahui pengaruh variasi kadar dan interaksi komponen penyusun tablet, yaitu etil selulosa (XA), tablettose (XB) dan magnesium stearat (XC) terhadap sifat fisik massa tablet dan pelepasan propranolol HCl, serta untuk menentukan rancangan formula optimum tablet lepas lambat propranolol HCl yang dibuat secara kempa langsung. Penelitian menggunakan factorial design 23, yaitu faktor XA, XB dan XC dengan low level berturut-turut 100%, 0% dan 0,25% serta high level berturutturut 400%, 200% dan 2%. Nilai level dinyatakan dari jumlah propranolol HCl yang digunakan, kecuali level magnesium stearat yang dinyatakan dari berat tablet. Sifat alir (Indeks Tap, %), homogenitas (CV,%), dan kompaktibilitas (kekerasan tablet, kg) digunakan sebagai parameter sifat fisik massa tablet, sedangkan tetapan kecepatan pelepasan obat dan koefisien korelasi kinetika orde nol sebagai parameter pelepasan obat. Signifikansi pengaruh faktor/interaksi dievaluasi berdasarkan Yates treatment dilanjutkan Anova. Makin besar kadar etil selulosa secara signifikan memperbaiki sifat alir, kompaktibilitas, dan koefisien korelasi orde nol, serta mengurangi homogenitas dan tetapan kecepatan pelepasan obat. Semakin besar kadar tablettose secara signifikan memperbaiki sifat alir dan mengurangi koefisien korelasi orde nol. Makin besar kadar magnesium stearat secara signifikan mengurangi kompaktibilitas, tetapan kecepatan pelepasan dan koefisien korelasi orde nol. Interaksi etil selulosa-tablettose secara signifikan mengurangi sifat alir dan kompaktibilitas serta memperbesar tetapan kecepatan pelepasan dan koefisien korelasi orde nol. Interaksi etil selulosa-magnesium stearat mengurangi kompaktibilitas, tetapan kecepatan pelepasan dan koefisien korelasi orde nol secara signifikan. Interaksi etil selulosa-tablettose-magnesium stearat secara signifikan mengurangi tetapan kecepatan pelepasan obat. Berdasarkan superimposed contour plot dan respon teoritis untuk berbagai parameter di atas, formula dengan kombinasi level XA, XB dan XC berturut-turut pada level +1 (320 mg), 0,232 (98,56 mg) dan –1 (1,25 mg) merupakan formula optimum yang secara teoritis menghasilkan sifat alir (Indeks Tap) 14%, homogenitas (CV) 3,42%, kompaktibilitas (kekerasan tablet) 11,25 kg dan mempunyai profil pelepasan obat mengikuti orde nol dengan tetapan kecepatan pelepasan 0,14% per menit, koefisien korelasi sebesar 0,9819 serta mekanisme pelepasan secara erosi dan difusi.

Matrix system of the tablet controls the drug release rate by erosiondiffusion system depending on the combination of matrix forming material (ethyl cellulose), channelling agent (tablettose) and the hydrophobic lubricant (magnesium stearate). Tablet quality was influenced by the physical properties of tablet mass. Therefore, the aim of this study was to investigate the effects of the concentrations variation and the interaction of the tablet component s, i.e. ethyl cellulose (XA), tablettose (XB) and magnesium stearate (XC) on the physical properties of the tablet mass and the release of propranolol HCl, and to determine the design of the optimum formula of controlled release propranolol HCl tablet, produced by direct compression method. Factorial design was used with 23, i.e. XA, XB, and XC with low level of 100, 0, and 0.25%, respectively and high leve l of 400, 200, and 2%, respectively. All level was from propranolol HCl weight, except for ma gnesium stearate, level was from tablet weight. The physical property parameters of the tablet mass were flowability (Index Tap, %), homogeneity (CV, %) and compactibility (tablet hardness, kg), while the released rate constant and correlation coefficient of zero order kinetics as the parameters for dissolution. The significancy of the factor/interaction effects were tested with Yates treatment followed by Anova. Increasing of ethyl cellulose concentration significantly increased the flowability, compactibility, zero order coefficient correlation and decreased the homogeneity and released rate constant. Increasing tablettose concentration significantly improved flowability and decreased zero order correlation coefficient. Increasing magnesium stearate concentration significantly decreased the compactibility, zero order released rate constant and correlation coefficient. Ethyl cellulose-tablettose interaction significantly decreased the flowability and compactibility, whereas zero order released rate constant and correlation coefficient were increased. Ethyl cellulose-magnesium stearate interaction significantly decreased the compactibility, zero order released rate constant and correlation coefficient. Ethyl cellulose-tablettose-magnesium stearate interaction significantly decreased the zero order release rate constant. Based on the superimposed contour plots and the theorytical responses, tablet formula consisting of XA, XB dan XC at the levels of +1 (320 mg), 0.232 (98.56 mg) and –1 (1.25 mg), respectively, was chosen as the optimum tablet formula. This formula theorytically has flowability (Index Tap) of 14%, homogeneity (CV) of 3.42%, compactibility (tablet hardness) of 11.25 kg, zero order release rate constant of 0.14% minutes-1 and correlation coefficient of 0.9819 with the drug release mechanism by erosion-diffusion systems

Kata Kunci : Obat Tablet,Formula,Sediaan Lepas Lambat,Propanolol HCl, propranolol HCl, ethyl cellulose, tablettose, magnesium stearate, physical properties of tablet mass, drug release, matrix system tablet