PENGARUH PEMBENTUKAN KOMPLEKS ?-SIKLODEKSTRIN TERHADAP DISOLUSI SIMVASTATIN DALAM BEBERAPA MEDIUM DISOLUSI

• Main Author: Felianti Putri, Tifani
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/45396
• Institution: Institut Teknologi Bandung

Simvastatin (SV) is categorized as Class 2 drug in the Biopharmaceutical Classification System. Simvastatin has a very low solubility in water i.e 0.03 mg/mL, at 25°C causing low dissolution rate and bioavailability of simvastatin. Improving the dissolution rate of a substance in water can be done by forming inclusion complexes using ?-cyclodextrin (BCD). The aim of this study is to determine the effects of the formation of inclusion complexes BCD against the dissolution of simvastatin. Preparation of inclusion complexes were made by kneading and grinding methods with SV:BCD 1:1 and 1:2 mol ratio in which the mixing time was previously optimized. Evaluations of inclusion complexes were done through solubility test, dissolution test, infrared spectrophotometry (FTIR), and Scanning Electron Microscope (SEM). Inclusion complexes dissolution tests were carried out in aquadest (A), simulated gastric fluid without enzyme (SGFw), simulated intestinal fluid without enzyme (SIFw), and surfactant buffer pH 7 (USP). Furthermore, each of the SV and the inclusion complex that has the highest dissolution rate was made into tablet. The optimal mixing time of inclusion complexes formation by kneading and grinding method was 45 and 60 minutes. The amount of SV dissolved in water was 23 and 23.59 ppm. The highest dissolution rate was showed by SV-BCD inclusion complex grinding method with ratio 1:2 with the percentage of dissolution 35.10 ± 1.04% (A), 28.75 ± 1.39% (SGFw), 17.75 ± 1.72% (SIFw), 99.55 ± 0.89% (USP). Results in FTIR showed that there was a specific shift in wave number of simvastatin compared to the pure simvastatin, which indicated the formation of complexes. Crystal morphology characterization of inclusion complexes using SEM appeared as aggregates, whilw SV was attached into the cavity of BCD. Tablets that were made from SV: BCD 1: 2 grinding method has a higher dissolution rate than pure simvastatin tablets with percentage of dissolution 110.13 ± 2.55 % (USP) and 35.97 ± 2.09 % (A). Based on the one-way ANOVA statistical test with Post Hoc LSD, the dissolution rate of inclusion complex’s tablet proved there were significant different values with pure simvastatin tablets and simvastatin tablets on the market. In conclusion, formation of ?-cyclodextrin inclusion complex did increase the rate of dissolution of simvastatin in the medium of aquadest, simulated gastric fluid without enzyme, simulated intestinal fluid without enzyme, and surfactant buffer pH 7. The highest dissolution rate was found in SV-BCD inclusion complex formed by grinding method with mol ratio 1:2 with 60 minutes mixing time. Surfactant has a big influence on the solubility and dissolution rate of simvastatin, therefore dissolution rate of pure simvastatin and complex did not look different.