DISSOLUTION ENHANCEMENT OF ENTACAPONE FROM FIXED DOSE COMBINATION TABLETS LEVODOPA/CARBIDOPA/ENTACAPONE WITH MICROENVIRONMENTAL PH MODIFICATION TECHNIQUES

• Main Author: Khairun Nisak, Rahmita
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/73968
• Institution: Institut Teknologi Bandung

Entacapone is a catechol nitro compound used in the treatment of Parkinson's disease in combination with carbidopa and levodopa. Entacapone is classified in Biopharmaceutical Classification System (BCS) 4, with low solubility and membrane permeability. Based on this, entacapone needs to be formulated appropriately to produce high bioavailability and maximum therapeutic effect. The bioavailability of BCS 4 drugs is determined by the rate of dissolution of the drug in the gastrointestinal fluid, so a technique is needed to formulate the drug. This study aims to develop formulation technique of fixed dose combination (FDC) tablet levodopa/ carbidopa/ entacapone through microenvironmental pH modification technique in order to increase dissolution rate of entacapone. Tablet formulations with microenvironmental pH modification technique are made by adding an alkalizing agent sodium carbonate or sodium bicarbonate with various concentrations. Tablets formulated using an alkalizing agent were evaluated by testing microenvironment pH at a certain time in dissolution medium HCl solution pH 1.2, acetate buffer solution pH 4.5, and phosphate buffer solution pH 6.8. The results showed microenvironment pH increase in the dissolution medium HCl solution pH 1.2 and acetate buffer solution pH 4.5. The results of the comparative dissolution test showed the FDC tablet formulation of carbidopa/ levodopa/ entacapone made with microenvironmental pH modification techniques could increase the dissolution rate of entacapone in all dissolution medium. The highest dissolution rate was shown by LOT 3, which is a tablet formulated with sodium carbonate 3%. In dissolution medium HCl solution pH 1.2, formula LOT 3 showed the best similarity with the comparator drug with f2 value 81.70, in acetate buffer solution pH 4.5, the best similarity was produced by formula LOT 4 with f2 value 76.81, and in phosphate buffer solution pH 6 ,8 the best similarity was produced by the formula LOT 0 with f2 value 50.47.