Although not life-threatening, acne can negatively affect the body and mind. Topical therapy of antibiotics agents are one of the important treatment for acne. Clarithromycin is a class II macrolide antibiotic. It is used in the treatment of severe acne and also in the treatment of soft tissue and skin diseases. With aim to enhance the solubility of Clarithromycin by preparing their solid dispersion using kneading and spray drying methods we prepared the solid dispersion of drug and polymer. Formulation F7 showed % CDR 90.80±2.67% at 60 min which is much higher than the % CDR of pure drug i.e. 25.66±0.77 at 60 min, therefore, it can be concluded that aqueous solubility of clarithromycin can be increased by complexing the drug with HP-β-CD and PVP K-30. The optimized solid dispersion powder (F7) was used to prepare the topical gel of clarithromycin. The optimized formulation G6 showed 82.99±2.70 % CDR at 720 min which is much higher than the % CDR of the pure drug. The significant antimicrobial activity of optimized Clarithriomycin gel formulation (G6) was found compared with marketed Clarithromycin gel formulation. The optimized formulation can be considered as promising and suitable for the topical application of clarithromycin into the skin for effective control of acne.