Preparation and evaluation of proliposomes containing clotrimazole.
Clotrimazole (CT)-containing proliposomes were prepared by penetrating an ethanol solution of CT and Egg phosphatidylcholine (PC) into microporous sorbitol particles, followed by vacuum evaporation of the solvent. As a result, CT proliposomes with free-flowing flowability were obtained. On contact with water, the proliposomes were rapidly converted into a liposomal dispersion, in which a certain amount of CT was entrapped by the liposomes. The result in scanning electronic micrograph confirmed the formation of liposomes structures from proliposomes, and the particles revealed round or ellipse. The ratio of drug to total lipid, ratio of PC to cholesterol and ratio of lipid to sorbitol affected the entrapment efficiency (EE%). The EE% of optimized formulation (CT 10 mg, 0.1 g total lipid, PC/CH ratio is 60 : 40 and 1 g sorbitol) in this investigation was 96.2+/-1.5%. The proliposomes system can provide sustaining release in simulated vaginal fluid at 37+/-1 degrees C for 24 h. In-vivo performance of blank proliposomes, a physical mixture of sorbitol and drug, clotrimazole proliposomes and commercial ointment formulation were evaluated using antifungal activity test. At 7 d post-dose, the c.f.u. of C. albicans decreased in proliposomes-treated groups than ointment and the physical mixture (t-Student, p<0.05). The results indicated that CT-containing vaginal proliposomes prolonged drug release and may increase amount of drug retention into the mucosa to result in more antifungal efficacy. In addition, CT-proliposomes did not affect the morphology of vaginal tissues. Therefore, the dosage form might be further developed for safe, convenient, and effective treatment of vaginal candidasis with reduced dosing interval.
Ning
Mei-Ying
MY
Chinese Academy of Medical Science & Peking Union Medical College, No. 9, Dongdan No. 3 avenue, Beijing 100730, PR China. mayning999@yahoo.com.cn
Guo
Ying-Zhi
YZ
Pan
Huai-Zhong
HZ
Yu
He-Ming
HM
Gu
Zhong-Wei
ZW
D000818:Animals; D003022:Clotrimazole / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008081:Liposomes; D011355:Prodrugs / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014621:Vagina / Q000166:cytology / Q000187:drug effects
D008081:Liposomes; D011355:Prodrugs; D003022:Clotrimazole