Effects of synthesis conditions and release medium pH on release properties of acyclovir - mercaptopropyl modified silica composite.

OBJECTIVE: The purpose of the present study was to evaluate the prospect of use of mercaptopropyl modified silica as a platform for development of new oral formulation of antiviral drug acyclovir (ACV) which is able to control release of the drug irrespective of release medium pH. METHODS: The composites of ACV with mercaptopropyl modified silica were synthesized using sol-gel technology under different conditions (synthesis pH, drug loading). The composites were characterized using scanning electron microscopy, dynamic light scattering and differential scanning calorimetry methods. The effects of the synthesis conditions on physicochemical properties of the prepared composites and their release properties were studied. RESULTS: The sol-gel synthesis conditions and release medium pH influence significantly release properties of the composites. The influence was explained by contributions of different factors, such as the drug-silica interactions in the composites, structure of the silica matrix and its stability in release media, hydrophobic nature of ACV, its pH-dependent solubility. It was found that all the synthesized composites followed the zero-order kinetics which is controlled by anomalous diffusion. CONCLUSION: The studies showed that the composites exhibited controlled release of ACV up to 80 h. However, the release properties of the drug depend significantly on pH of release medium, i.e. the release properties (the release rate, the amount of released ACV) will change during transition of the composites through various segments of GIT. Therefore, the synthesized composites are not a promising basis for development of new oral dosage form of ACV.

Development of Novel Silica-based Formulation of α-Lipoic Acid: Evaluation of Photo and Thermal Stability of the Encapsulated Drug.

Powerful antioxidant α-lipoic acid (LA) is easily degraded under light and heating. This creates difficulties in its manufacture, storage and reduces efficiency and safety of the drug. The purpose of this work was to synthesize novel silica-based composites of LA and evaluate their ability to increase photo and thermal stability of the drug. It was assumed that the drug stabilization can be achieved due to LA-silica interactions. Therefore, the composites of LA with unmodified and organomodified silica matrixes were synthesized by sol-gel method at the synthesis pH below or above the pKa of the drug. The effects of silica matrix modification and the synthesis pH on the LA-silica interactions and kinetics of photo and thermal degradation of LA in the composites were studied. The nature of the interactions was revealed by FTIR spectroscopy. It was found that the rate of thermal degradation of the drug in the composites was significantly lower compared to free LA and mainly determined by the LA-silica interactions. However, photodegradation of LA in the composites under UV irradiation was either close to that for free drug or significantly more rapid. It was shown that kinetics of photodegradation was independent of the interactions and likely determined by physical properties of surface of the composite particles (porosity and reflectivity). The most promising composites for further development of novel silica-based formulations were identified.