title: Development of Clotrimazole Multiple W/O/W Emulsions as Vehicles for Drug Delivery: Effects of Additives on Emulsion Stability.
abstract: Multiple emulsions have attracted considerable attention in recent years for application as potential delivery systems for different drugs. The aim of the present work is to design a new formulation containing clotrimazole (CLT) loaded into multiple emulsions by two-step emulsification method for transdermal delivery. Different ingredients and quantities like primary and secondary co-emulsifiers and the nature of oily phase were assayed in order to optimize the best system for good. Resulting formulations were characterized in terms of droplet size, conductivity, pH, entrapment efficiency, rheological behavior, and stability under various storage conditions for 180 days. pH values of multiple emulsions containing CLT ranged from 7.04 ± 0.03 to 6.23 ± 0.04. Droplet size increased when increasing concentration of sorbitan stearate. The addition of polysorbate 80 resulted in significant decrease of oil droplet size comparing with those prepared without this. CLT entrapment efficiency ranged between 85.64% and 97.47%. All formulations exhibited non-Newtonian pseudoplastic flow with some apparent thixotropic behavior. Cross and Herschel-Bulkley equations were the models that best fitted experimental data. In general, the addition of 1% polysorbate 80 resulted in a decrease of viscosity values. No signals of optical instability were observed, and physicochemical properties remained almost constant when samples were stored at room temperature after 180 days. On the contrary, samples stored at 40°C exhibited pronounced increase in conductivity values 24 h after elaboration and some of them were unstable after 180 days of storage. JMLP01 was proposed as an innovative and stable system to incorporate CLT as active pharmaceutical ingredient.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Suñer
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Calpena
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain. beatrizclares@ugr.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Clares
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cañadas
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Lyda
authors.initials: L
authors.lastname: Halbaut
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003022:Clotrimazole / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D012212:Rheology; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity
chemical_list: D004655:Emulsions; D005079:Excipients; D009821:Oils; D011136:Polysorbates; D013501:Surface-Active Agents; D003022:Clotrimazole
keywords: clotrimazole; multiple emulsion; rheology; stability