Tasdighi Elahe, Jafari Azar Zahra, Mortazavi Seyed Alireza
Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2012 Winter;11(1):13-26.
The objective of the present investigation was to develop and evaluate a contraceptive vagino-adhesive propranolol hydrochloride gel. To achieve this, various mucoadhesive polymers including guar gum (1-4% w/w), sodium alginate (4-7% w/w), xanthan gum (2-5% w/w ), HPMC 4000 (3-5% w/w), Na CMC (4-7% w/w), carbomer 934 and carbomer 940 both in the range of 0.5-2.0% w/w, were dispersed in an aqueous-based solution containing the drug (1.6% w/w). The mucoadhesive properties of the gels were assessed on sheep vaginal mucosa (as model mucosa) in pH 4.5 citrate-phosphate buffer at 37°C. Formulations containing charged functional groups in their polymeric structure, showed higher mucoadhesive strengths in comparison to those composed of neutral polymers. In-vitro drug release profiles of the gels were determined in pH 4.5 citrate-phosphate buffer. Results indicated that, only formulation F13 (containing sodium alginate 6.5% w/w), could release its drug over 12 h, with a burst release at the initial phase followed by a sustained release pattern. This formulation, which showed a good mucoadhesive strength (386.97 ± 9.31 mN), was considered as the final formulation and underwent complementary tests including determination of drug content and duration of mucoadhesion. Its drug content was found to be 101.05 ± 0.106% (n = 3) and it attached to the model mucosa for more than 10 h. In conclusion, formulation F13 was considered as the most desirable formulation as it exhibited appropriate mucoadhesive properties while having the potential of providing an immediate contraceptive effect, followed by a prolonged drug release which is assumed to render longer contraceptive efficacy.
本研究的目的是开发并评估一种含盐酸普萘洛尔的阴道黏附性避孕凝胶。为此，将各种黏膜黏附聚合物分散于含药物（1.6% w/w）的水基溶液中，这些聚合物包括瓜尔胶（1 - 4% w/w）、海藻酸钠（4 - 7% w/w）、黄原胶（2 - 5% w/w）、羟丙甲纤维素4000（3 - 5% w/w）、羧甲基纤维素钠（4 - 7% w/w）、卡波姆934和卡波姆940，含量均在0.5 - 2.0% w/w范围内。在37℃、pH 4.5的柠檬酸 - 磷酸盐缓冲液中，以绵羊阴道黏膜（作为模型黏膜）评估凝胶的黏膜黏附特性。聚合物结构中含有带电官能团的制剂，与由中性聚合物组成的制剂相比，表现出更高的黏膜黏附强度。在pH 4.5的柠檬酸 - 磷酸盐缓冲液中测定凝胶的体外药物释放曲线。结果表明，只有制剂F13（含6.5% w/w海藻酸钠）能在12小时内释放药物，初始阶段有突释，随后呈持续释放模式。该制剂表现出良好的黏膜黏附强度（386.97 ± 9.31 mN），被视为最终制剂，并进行了补充试验，包括药物含量测定和黏膜黏附持续时间测定。其药物含量为101.05 ± 0.106%（n = 3），且在模型黏膜上附着超过10小时。总之，制剂F13被认为是最理想的制剂，因为它具有适当的黏膜黏附特性，同时有可能提供即时避孕效果，随后药物持续释放，这被认为可带来更长时间的避孕效果。
