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This study involves the fabrication of a dosage form for acne treatment. A semi-solid dosage form of microsponge loaded topical gel with benzoyl peroxide and poly lactic-co-glycolic acid (PLGA) was developed. Formulation was prepared using PLGA, span, and polyvinyl alcohol. Optimization of the formulation was done by design of experiments response surface methodology using a central composite method. The microsponge was prepared by a quasi-emulsion solvent diffusion method. Central composite experimental design was used for optimization of the formulation with respect to entrapment efficiency and in vitro drug release. A benzoyl peroxide-loaded PLGA microsponge formulation was prepared and characterized with respect to drug content, drug release, and morphology. Drug release was found to be 52.42% for PLGA-loaded microsponges. The optimized microsponges containing PLGA were converted into a topical gel using benzoyl peroxide as a drug. Carbopol was used as a gelling agent for the optimized microsponge formulation containing PLGA. The gel showed pseudoplastic behavior with a high value of spreading capacity. It was translucent without the presence of foreign particles. Evaluation parameters for microsponges loaded topic gel, such as determination of pH (5.82), spreadability (5.9), viscosity 50 rpm (1253 cp), drug content (98.07%), and in vitro drug release (50.42), were performed for the designed topical semi-solid dosage form. [ABSTRACT FROM AUTHOR]