didanosine and ethyl-cellulose

Inert matrices of didanosine (ddI) were elaborated as controlled release dosage forms, using two different types of polymers: Eudragit RS-PM, an anionic acrylic acid copolymer, and Ethocel 100 Premium, an ethylcellulose. A preformulation study of the drug was designed to address the following points: (a) the development of two alternative methods (high performance liquid chromatography (HPLC) and UV spectrophotometry) for the analysis and quantifying of ddI; (b) the determination of the aqueous solubility of ddI; and (c) the characterization of ddI from the following points of view: morphological (scanning electronic microscopy (SEM)) and thermal (differential scanning calorimetry (DSC)). Furthermore, some of these techniques were used for the characterization of those components which will be included in the oral controlled release system to be developed. The in vitro release of ddI matrices was studied at pH 7.4, because of the instability of ddI at pH values lower than 3 units. A significant reduction in the release rate of drug from both ddI controlled release systems was found. Furthermore, Ethocel 100 Premium showed a minor efficiency in the dissolution process, with a reduction of more than double in the final dissolution efficiency (DE) value. This parameter and the fit factors (f1 and f2) have been compared for the characterization of dissolution profiles.

Topics: Acrylic Resins; Cellulose; Delayed-Action Preparations; Didanosine; Solubility

Didanosine, a nucleoside analog used in the treatment of acquired immuno deficiency syndrome (AIDS), has been incorporated into directly compressed monolythic matrices whose excipients were mixtures at different ratios of a methacrylic resin (Eudragit RSPM) and an ethylcellulose (Ethocel 100), both water-insoluble and pH-independent polymers. Technological characterization (drug particle morphology, mean weight, diameter, thickness and hardness of tablets) was carried out and in vitro drug release behaviour was measured using the USP basket apparatus. The effect of varying the Eudragit-Ethocel ratio, as well as the drug-polymeric matrix ratio, was evaluated. The results showed the suitability of Eudragit-Ethocel mixtures as matrix-forming material for didanosine sustained release formulations. Combination of the moderate swelling properties of Eudragit RSPM with the plastic properties of the more hydrophobic Ethocel 100 allowed suitable modulation of didanosine release.

Topics: Anti-HIV Agents; Cellulose; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Didanosine; Hardness; Hydrogen-Ion Concentration; Image Processing, Computer-Assisted; Methacrylates; Microscopy, Electron, Scanning; Particle Size; Polymers