Carlo Ceschel Gian, Bergamante Valentina, Calabrese Valeria, Biserni Stefano, Ronchi Celestino, Fini A
Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy.
Drug Dev Ind Pharm. 2006 Jan;32(1):53-61. doi: 10.1080/03639040500388300.
This investigation deals with the development of buccal tablets containing chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects in the oral cavity, and able to adhere to the buccal mucosa to give local controlled release of drug. A mucoadhesive formulation was designed to swell and form a gel adhering to the mucosa and controlling the drug release into the oral cavity. Some batches of tablets were developed by direct compression, containing different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing the amount ratio of these excipients in formulations, it is possible easily modulate the mucoadhesive effect and release of drug. The in vitro tests were performed using the USP 26/NF paddle apparatus, a specifically developed apparatus, and a modified Franz diffusion cells apparatus. This last method allows a simultaneous study of drug release rate from the tablets and drug permeation through the buccal mucosa. Similar tests have also been carried out on a commercial product, Corsodyl gel, in order to compare the drug release control of gel with respect to that of the mucoadhesive tablet, as a formulation for buccal delivery of CHX. While the commercial formulation does not appear to control the release, the formulation containing 15% w/w methocel behaves the best, ensuring the most rapid and complete release of the drug, together with a negligible absorption of the active agent as required for a local antiseptic action in the oral cavity.
本研究涉及含氯己定（CHX）的口腔贴片的开发。氯己定是一种双胍类化合物，在口腔中具有抗菌和防腐作用，能够粘附于口腔黏膜以实现药物的局部控释。设计了一种黏膜粘附制剂，使其膨胀并形成一种凝胶，粘附于黏膜并控制药物向口腔内释放。通过直接压片法制备了几批片剂，其中含有不同量的羟丙基甲基纤维素（HPMC）和卡波姆；通过改变制剂中这些辅料的用量比例，可以轻松调节黏膜粘附效果和药物释放。体外试验使用USP 26/NF桨法装置（一种专门开发的装置）和改良的弗兰兹扩散池装置进行。后一种方法可以同时研究片剂的药物释放速率和药物透过口腔黏膜渗透的情况。还对一种市售产品——洗必泰凝胶进行了类似试验，以便比较凝胶与黏膜粘附片作为CHX口腔给药制剂在药物释放控制方面的差异。虽然市售制剂似乎无法控制释放，但含15% w/w甲基纤维素的制剂表现最佳，能确保药物最快速、最完全地释放，同时活性成分的吸收可忽略不计，这是口腔局部防腐作用所要求的。
