Optimasi proporsi campuran PVP-K29/32 - L-HPC LH-11 - Na Lauril Sulfat untuk formula tablet Asam Mefenamat

HARAHAP, Abdul Kholik, Prof.Dr. Sri Sulihtyowati Soebagyo, Apt

2005 | Tesis | S2 Ilmu Farmasi

Asam mefenamat mempunyai sifat alir dan kelarutan yang jelek dan cenderung melengket pada permukaan stempel dan matrik mesin tablet. Oleh karenanya akan bermasalah dalam pemb uatan tablet dan disolusinya. Penelitian ini bertujuan mengetahui pengaruh PVP K-29/32 (bahan pengikat), L-HPC LH- 11(bahan penghancur) dan Na lauril sulfat (bahan pembasah) dan interaksinya terhadap sifat-sifat fisik granul asam mefenamat dan disolusi asam mefenamatnya serta mendapatkan formula optimum tablet asam mefenamat yang memenuhi persyaratan yang dibuat secara granulasi basah. Dalam formula tablet asam mefenamat 500 mg, dengan berat tablet 700 mg digunakan campuran PVP K-29/32– L-HPC LH-11– Na lauril sulfat yang jumlahnya 22,5 mg, proporsinya dioptimasikan secara simplex lattice design special cubic model (optimasi untuk 3 jenis komponen). Pada model special cubic digunakan 7 formula (yaitu 3 formula dengan vertex A (PVP-K29/32), B (L-HPC LH-11) dan C (Na lauril sulfat) masing-masing sebanyak 100 %, 3 formula campuran 50 % - 50 % pasangan AB, AC dan BC dan 1 formula campuran ABC masing-masing 331/3 %) untuk mendapatkan koefisien persamaan Y = B1(A) + B2(B) + B3(C) + B12(A)(B) + B13(A)(C) + B23(B)(C) + B123(A)(B)(C) untuk masing-masing parameter granul asam mefenamat. Dari masing-masing persamaan tersebut didapat contour plot, dan superimposed contour plot sehingga dapat dipilih formula optimum. Disimpulkan PVP K-29/32 merupakan faktor yang paling dominan memperbaiki kecepatan alir dan kompaktibilitas granul asam mefenamat, L-HPC LH-11 merupakan faktor yang paling dominan mempengaruhi disolusi (C-60) sedangkan interaksi antara L-HPC LH-11 dengan Na lauril sulfat paling dominan memperbaiki kecepatan alir, interaksi ketiganya untuk memperbaiki kompaktibilitas, sedangkan interaksi antara L-HPC LH-11 dengan Na lauril sulfat merupakan faktor yang dominan untuk memperbaiki disolusi (C-60). Campuran PVP K-29/32– L-HPC LH-11 dan Na lauril sulfat dengan proporsi berturut-turut 0,396 - 0,300 dan 0,304 bagian memberikan hasil yang optimum pada tablet asam mefenamat dengan kekerasan 5,069 + 0,1827 kg, kerapuhan 0,964 + 0,4126 %, waktu hancur 177,8 + 2,70 detik dan disolusi asam mefenamat pada menit ke 60 sebesar 57,441 + 1,1829 %.

Mefenamic acid has bad flowability and solubility, and it tends to stick to the surface of punch and dies of tablet machine. Therefore there will be problem on tablet production and dissolution. The study was to identify each effect of PVP K-29/32 (binding agent), L-HPC LH-11 (disintegrating agent) and Na lauryl sulfate (wetting agent) and their interaction effect on physical properties of mefenamic acid granules and the dissolution of mefenamic acid as well as to find the optimum formula of mefenamic acid tablet produced by wet granulation that fulfilled the tablet requirement. The mixture of PVP K-29/32 - L-HPC LH-11 - Sod lauryl sulfate in the total weight of 22,5 mg in which their proportion was optimized by using simplex lattice design special cubic model (optimization for 3 components). This mixture was used in the mefenamic acid 500 mg tablet formula of 700 mg tablet weight. In the special cubic model 7 formulas were applied: 3 formula with the vertex of A (PVP K-29/32), B (L-HPC LH-11) and C (Na Lauryl Sulfate) each in amount of 100 %, 3 formula in the combination of 50-50 % (AB, AC, and BC) and 1 formula in a combination of ABC (33,33% of each) to get the coefficient of equation Y = B1(A) + B2(B) + B3(C) + B12 (A)(B) + B13 (A)(C) + B23(B)(C) + B123(A)(B)(C) for each of mefenamic acid granules parameters. Using these equations, the contour plots were obtained, as well as the superimposed of contour plots from which the optimum formula could be selected. It was concluded that PVP K-29/32 was the most dominant increasing factor on flowability and compactibility of mefenamic acid granules. L-HPC LH- 11 was the dominant increasing factor on dissolution (C-60), while the most dominant interaction effect to increase flowability was between L-HPC LH-11 and Na lauryl sulfate. To increase compactibility it was the interaction of the three PVP K-29/32, L-HPC LH-11 and Na lauryl sulfate as the dominant factor. The mixture PVP K-29/32 – L-HPC LH-11 and Na lauryl sulfate with portion of 0,396, 0,300 and 0,304 respectively, gave the optimum result on the mefenamic acid tablet with the hardness of 5,069 + 0,1827 kg, friability of 0,964 + 0,4126 %, disintegration time of 177,8 + 2,70 second and the mefenamic acid dissolution at 60 minutes was 57,441 + 1,1829 %.

Kata Kunci : Obat ANalgetik,Tablet Asam Mefenamat,Campuran PVP K29/32,L,HPC LH,11,Na Lauril Sulfat, mefenamic acid, PVP K-29/32, L-HPC LH-11, Na lauryl sulfate, flowability, compactibility, dissolution