Clotrimazole nanoemulsion for malaria chemotherapy. Part I: preformulation studies, formulation design and physicochemical evaluation.
Clotrimazole was formulated in nanoemulsion based system with the aim of improving its solubility and dissolution, which can further used for its preclinical evaluation. Clotrimazole nanoemulsion was prepared using spontaneous nanoemulsification method. Preformulation studies were preformed to evaluate drug-excipient compatibility, solution state pH stability and pH solubility profile. Solubility of clotrimazole in oils, surfactants and cosurfactants was determined to identify nanoemulsion components. Surfactants and cosurfactants were screened for their ability to emulsify selected oily phases. Phase diagrams were constructed to identify area of nanoemulsification. Influence of clotrimazole and pH of dilution medium on phase behavior were assessed. Drug-excipient chemical compatibility study facilitated to anticipate acid catalyzed degradation of clotrimazole. The pH of nanoemulsion was adjusted to 7.5, which could stabilize clotrimazole. Nanoemulsion composed of Capryol 90, Solutol HS 15 and Gelucire 44/14 enhanced solubility of clotrimazole up to 25mg/ml. The optimized clotrimazole nanoemulsion could withstand the extensive dilution and did not show any phase separation or drug precipitation. The nanoemulsion exhibited mean globule size <25 nm, which was not affected by pH of dilution medium. Dissolution profile of clotrimazole nanoemulsion in various media showed 100% drug release within 15 min irrespective of pH of medium.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India. vivekborhade@gmail.com
Vivek
V
Borhade
Sulabha
S
Pathak
Shobhona
S
Sharma
Vandana
V
Patravale
D000962:Antimalarials / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003022:Clotrimazole / Q000737:chemistry*; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D049329:Nanostructures / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
D000962:Antimalarials; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; D003022:Clotrimazole