Development and evaluation of biodegradable microspheres embedded in in situ gel for controlled delivery of hydrophilic drug for treating oral infections: In vitro and in vivo studies

Abstract

Present investigation was aimed at developing biodegradable polymeric microspheres of Tetracycline hydrochloride to treat oral infections by using Poly (D, L lactic‑co‑glycolic) acid (50:50) as polymer. Microspheres were prepared using oil‑in‑oil (O/O) and water‑in‑oil‑in‑water (W/O/W) double emulsion solvent evaporation method. Microspheres prepared by W/O/W were spherical in shape compared those prepared with O/O method. Thus, the microspheres formulated by W/O/W method were further evaluated for particle size, morphology, entrapment efficiency, and percent drug release. Effects of salt addition, polymer concentration on the characteristics of microspheres and tetracycline release profile were investigated. An increase in polymer concentration decreased drug release and increased entrapment efficiency of drug. In vitro studies indicated that release of drug from microspheres could be controlled for 10-15 days depending on drug: Polymer concentration. Formulation E released 99.10% of drug from microspheres in 10 days. Addition of sodium chloride to outer aqueous phase produced spherical microspheres with smooth surface and also increased entrapment efficiency. Microspheres were further dispersed in optimized formulation of mucoadhesive in situ gel of Pluronic F127, which acts as carrier for microspheres. In vivo studies were conducted on patients who underwent molar tooth extraction to check efficacy of designed formulation. Key words: Double emulsion, in situ gel, microspheres, molar tooth extraction, poly (D, L lactic‑co‑glycolic) acid, tetracycline hydrochloride