USAHA PENINGKATAN LAJU DISOLUSI ALLOPURINOL MENGGUNAKAN METODE DISPERSI PADAT DENGAN BERBAGAI PEMBAWA

• Main Author: Agustina Surono, Linda
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/64316
• Institution: Institut Teknologi Bandung

Allopurinol is commonly use drug for treatment of hyperuricemic or chronic gout. This substance is slightly soluble in water, but has a good penetration in biological membrane, so it dissolution rate is the limiting step for absorption process and the bioavailability of oral drug administration. The aim of this study is to improve the dissolution rate of allopurinol with solid dispersion technique using PEG 4000, mannitol, and Avicel PH 101 as the carrier. Solid dispersions are made in 1:1 and 1:2 weight ratio using solvent evaporation method for Avicel PH 101 and Mannitol as carrier. Kneading method and suspension method are also used for Avicel PH 101. Melting method is used for PEG 4000 as a carrier. The dissolution testing for allopurinol, physical mixture, and the solid dispersion were performed in the medium HCI 0, IN of pH 1,2; using type 2 apparatus and rotation of 75 rpm. The solubility of allopurinol, physical mixture, and it solid dispersion are determined in water media using orbital shaker, at 100 rpm and temperature 37°C. The morphology of solid dispersion were characterized using Scanning Electron Microscope (SEM) and the interactions of allopurinol and the carrier are identified with fourier transform infrared (FTIR) spectroscopy. Then the solid dispersion that showed highest dissolution rate is compressed into tablet. Preparation of solid dispersion with Avicel PH 101 using solvent evaporation method (A LD 1:2) can improve the dissolution of allopurinol but not an efficient method because it is needed 3.3 L of ethanol to dissolve 1 gr of allopurinol. Whereas solid dispersion obtained from kneading method did not show significant improvement of allopurinol dissolution rate. Solid dispersion of allopurinol with Avicel PH 10 1 in 1:2 weight ratio (A TD 1:2) that prepared by suspension method and PEG 4000 in 1:2 weight ratio (P DP 1:2) formula showed the enhancement of dissolution rate that significantly different with pure allopurinol and the physical mixture. The amount (%) of pure allopurinol, A TD 1 :2 and P DP 1:2 dissolved were 43.19 ± 1.44%; 71.51 ± 8.78% and 94.53 + 0.39% respectively, after 5 minutes. The solid dispersion of allopurinol with mannitol did not show different dissolution rate with its physical mixture. The FTIR spectrum showed no interaction between the carrier and allopurinol in solid dispersion. Microphotograph obtained from SEM evaluation showed that the particles of allopurinol were adsorbed on the surface of Avicel PH 101 and the particle size seem to be reduced. The solid dispersion of A TD 1:2 tablets are made with direct compression technique. There was no significant difference of allopurinol dissolution rate from formula A TD 1:2 after it is compressed into tablets compared to its physical mixture tablets.