Lodhi Mohasin, Dubey Akhilesh, Narayan Reema, Prabhu Prabhakara, Priya Sneh
Department of Pharmaceutics, Shree Devi College of Pharmacy, Kenjar Village, Mangalore, Karnataka, India.
Int J Pharm Investig. 2013 Jan;3(1):47-53. doi: 10.4103/2230-973X.108963.
Ivabradine hydrochloride is an anti-anginal drug with a biological half-life of about 2 h, and repeated daily administration is needed to maintain effective plasma level. Present investigation of buccal films of Ivabradine hydrochloride is an attempt to avoid the repeated administration and release of drug in more controlled fashion, thereby, to improve the bioavailability.
Buccal patches were fabricated by solvent casting technique and were evaluated for its physical properties like physical appearance, weight uniformity, thickness, swelling index, surface pH, mucoadhesive time, and folding endurance, in vitro and ex vivo release studies.
A combination of hydroxypropyl methyl cellulose (HPMC) K15M and K100M with carbopol 940, PEG 6000 gave promising results. Further, the drug content of all the formulations was determined and was found to be uniform. All the formulations were subjected to in vitro release study using phosphate buffer pH 6.6. Patches exhibited drug release in the range of 90.36% ± 0.854 to 98.37% ± 0.589 at the end of six hrs. The best formulations (F2 and F5) containing the composition of HPMC K15-37.50 mg, carbopol-0.42 mg, PEG6000-16.87 mg, Aspertane-0.28 mg, Tween-0.0023 mg and HPMC K100-37.50 mg, carbopol-0.42 mg, PEG6000-16.87 mg, Aspertane-0.28 mg, Tween-0.0023 mg respectively exhibited in vitro drug release of 97.61% ± 0.589 and 98.37% ± 0.114 respectively. The results of ex vivo diffusion using goat cheek pouch revealed that the drug release rate was retarded up to seven hrs. Films prepared with permeation enhancer (Tween 80) showed faster drug release. Finally, stability studies were carried out by using human saliva for the optimized formulation (F2-F5).
The present study indicated enormous potential of mucoadhesive buccal patches containing Ivabradine for systemic delivery with an added advantage of circumventing hepatic first pass metabolism. Further work is recommended to support its efficacy claims by long term pharmacokinetic and pharmacodynamic studies in human beings.
盐酸伊伐布雷定是一种抗心绞痛药物，生物半衰期约为2小时，需要每日重复给药以维持有效的血浆水平。目前对盐酸伊伐布雷定口腔膜剂的研究旨在避免重复给药，并以更可控的方式释放药物，从而提高生物利用度。
采用溶剂浇铸技术制备口腔贴片，并对其外观、重量均匀性、厚度、溶胀指数、表面pH值、粘膜粘附时间和耐折性等物理性质进行体外和离体释放研究。
羟丙基甲基纤维素（HPMC）K15M和K100M与卡波姆940、聚乙二醇6000的组合产生了良好的效果。此外，测定了所有制剂的药物含量，发现其均匀。所有制剂均使用pH 6.6的磷酸盐缓冲液进行体外释放研究。贴片在6小时结束时的药物释放率在90.36%±0.854至98.37%±0.589之间。含有HPMC K15 - 37.50mg、卡波姆 - 0.42mg、聚乙二醇6000 - 16.87mg、阿斯巴甜 - 0.28mg、吐温 - 0.0023mg的最佳制剂（F2）和含有HPMC K100 - 37.50mg、卡波姆 - 0.42mg、聚乙二醇6000 - 16.87mg、阿斯巴甜 - 0.28mg、吐温 - 0.0023mg的最佳制剂（F5）分别表现出97.61%±0.589和98.37%±0.114的体外药物释放率。使用山羊颊囊进行的离体扩散结果表明，药物释放速率在7小时内受到抑制。用渗透促进剂（吐温80）制备的膜显示出更快的药物释放。最后，使用人唾液对优化制剂（F2 - F5）进行稳定性研究。
本研究表明含伊伐布雷定的粘膜粘附口腔贴片在全身给药方面具有巨大潜力，具有规避肝脏首过代谢的额外优势。建议进一步开展工作，通过对人类进行长期的药代动力学和药效学研究来支持其疗效声明。
