Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India.
Int J Pharm. 2012 Jul 15;431(1-2):138-48. doi: 10.1016/j.ijpharm.2011.12.040. Epub 2011 Dec 30.
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.
克霉唑被制成基于纳米乳的系统，目的是提高其溶解度和溶解速率，这可以进一步用于临床前评估。克霉唑纳米乳通过自发乳化法制备。进行了预配方研究以评估药物-赋形剂相容性、溶液状态 pH 稳定性和 pH 溶解度曲线。确定了克霉唑在油、表面活性剂和助表面活性剂中的溶解度，以确定纳米乳的组成。筛选了表面活性剂和助表面活性剂，以评估其乳化所选油性相的能力。构建相图以确定纳米乳化区域。评估了克霉唑和稀释介质 pH 对相行为的影响。药物-赋形剂化学相容性研究有助于预测克霉唑的酸催化降解。将纳米乳的 pH 调节至 7.5，这可以稳定克霉唑。由 Capryol 90、Solutol HS 15 和 Gelucire 44/14 组成的纳米乳将克霉唑的溶解度提高至 25mg/ml。优化的克霉唑纳米乳可以经受住广泛的稀释，并且不会发生任何相分离或药物沉淀。纳米乳的平均粒径<25nm，不受稀释介质 pH 的影响。在各种介质中克霉唑纳米乳的溶出曲线显示，无论介质的 pH 值如何，药物在 15 分钟内均可完全释放。
