Objectives: The objective of the present work is to develop and characterize metronidazole microsphere-loaded bioadhesive vaginal gel to ensurelonger residence time at the infection site, providing a favorable release profile for the drug.Methods: Microsphere was prepared by solvent evaporation method in various ratios of metronidazole to poly-ε-caprolactone (PCL). Physicochemicalevaluation of microspheres includes determination of solubility in simulated vaginal fluid, partition coefficient (n-octanol/citrate phosphatebuffer pH 4.5), particle size distribution, entrapment efficiency, X-ray diffraction, and surface morphology by scanning electron microscopy (SEM).Drug excipient compatibility was established by Fourier transform infrared and differential scanning calorimetry studies. Bioadhesive gel wasprepared using Carbopol 934P and HPMC K4M in various concentrations, and methyl paraben was used as a preservative. The pH was adjustedwith triethanolamine which resulted in a translucent gel. The optimized metronidazole microsphere formulation was dispersed into the gel base.Microspheres in gel formulations were evaluated for pH, viscosity, spreadability, drug content, and gelling strength. Ex vivo mucoadhesive strength ofthe gel was determined on goat vaginal mucosa. In vitro drug release study was performed using cellophane membrane.Results: The optimized batch of microsphere F4 (drug-polymer ratio 1:4) showed entrapment efficiency of 72.62±3.66%, solubility of 1.5 mg/ml, andpartition coefficient of 0.12. Particle size of all the formulations was observed below 100 μm. Regular and spherical particles were observed in theSEM photomicrographs. The optimized gel formulation G5 (Carbopol and HPMC at 1: 0.25 ratio) showed viscosity of 7538 cps at 100 RPM, gel strengthrecorded as 35 secobds for a 1000.00 mg load, and spreadability of 4.6 g.cm/seconds. G5 showed 82.4% drug release at 10.0 hrs and mucoadhesivestrength of 6.5±1.2 g.Conclusion: The study results suggest that metronidazole-loaded PCL microsphere in mucoadhesive gel would provide a mean for sustainedtreatment of vaginal infections.Keywords: Microsphere, Metronidazole, Bioadhesive vaginal gel.

Objective: The main objective of the present work is to develop and characterize a novel mucoadhesive intranasal microsphere gel formulation of drug venlafaxine to control the drug release through nasal mucosa and reach the target site with minimal side effect. The objectives of the study are (1) formulation of mucoadhesive microspheres, (2) evaluation of mucoadhesive microspheres, (3) formulation of mucoadhesive microsphereloaded nasal gel, (4) and evaluation of nasal gel.Methods: Preparation of chitosan microsphere: The chitosan microspheres were prepared by emulsion cross-linking method. Preparation of microsphere-loaded gel: The nasal gels with varying concentrations of Carbopol 934P were prepared by dispersing required quantity of Carbopol in required quantity of distilled water with continuous stirring and kept overnight for complete hydration. The gel was then modified by the addition of varying proportion of hydroxypropyl methylcellulose (HPMC) K4M. Results:The prepared microspheres were evaluated for size distribution, surface morphology by scanning electron microscopy, entrapment efficiency, compatibility by Fourier transform infrared spectroscopy, and differential scanning calorimetry. Entrapment efficiency of all formulations was found more than 70%. Microsphere formulation containing drug and polymer in the ratio of 1:2.5 was found to be optimized. Optimized microsphere formulation was then incorporated in gel prepared using Carbopol 934P and HPMC. Prepared gel formulations were studied for viscosity, spreadability, and in-vitro drug release in simulated nasal conditions. Viscosity of the optimized batch of gel was recorded at 1056 centipoise. Drug release was prolonged for the microsphere-in-gel formulations compared to the microspheres alone. For the optimized batch of gel, cumulative drug release of 85.67% was found after 8 hrs. Conclusion:The results suggest that venlafaxine hydrochloride mucoadhesive microsphere-loaded nasal gel would give sustained drug release and superior bioavailability in the brain sites.