Cappello Brunella, De Rosa Giuseppe, Giannini Lucia, La Rotonda Maria Immacolata, Mensitieri Giuseppe, Miro Agnese, Quaglia Fabiana, Russo Roberto
Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Int J Pharm. 2006 Aug 17;319(1-2):63-70. doi: 10.1016/j.ijpharm.2006.03.031. Epub 2006 Apr 25.
The aim of this work was to develop a tablet for the buccal delivery of the poorly soluble drug carvedilol (CAR), based on poly(ethyleneoxide) (PEO) as bioadhesive sustained-release platform and hydroxypropyl-beta-cyclodextrin (HPbetaCD) as modulator of drug release. As first, PEO tablets loaded with CAR/HPbetaCD binary systems with different dissolution properties were tested for CAR and HPbetaCD release features and compared to PEO tablets containing only CAR. When the drug was incorporated as CAR/HPbetaCD freeze-dried product, all CAR content was released from the tablet in about 10 h, displaying a constant release regimen after a transient. The effect of HPbetaCD incorporation on the release mechanism, was rationalized on the basis of the interplay of different physical phenomena: erosion and swelling of the tablet, drug dissolution, drug counter-diffusion and complex formation. In the second part of the study, the potential of HPbetaCD-containing PEO tablets as buccal delivery system for CAR was tested. It was found that the incorporation of HPbetaCD in the tablet did not alter significantly its good adhesion properties. The feasibility of buccal administration of CAR was assessed by permeation experiments on pig excised mucosa. The amount of CAR permeated from PEO tablet was higher in the case of HPbetaCD-containing tablets, the maximum value being obtained for CAR/HPbetaCD freeze-dried system. Our results demonstrate that, when the tablet is employed as transmucosal system, the role of drug dissolution enhancement in the hydrated tablet is much more relevant than in solution for increasing the delivery rate.
本研究旨在开发一种用于难溶性药物卡维地洛（CAR）口腔给药的片剂，该片剂以聚环氧乙烷（PEO）作为生物黏附性缓释平台，以羟丙基-β-环糊精（HPβCD）作为药物释放调节剂。首先，对载有具有不同溶解特性的CAR/HPβCD二元体系的PEO片剂进行了CAR和HPβCD释放特性测试，并与仅含CAR的PEO片剂进行了比较。当药物以CAR/HPβCD冻干产物形式加入时，所有CAR含量在约10小时内从片剂中释放出来，在短暂的过渡期后呈现出恒定的释放模式。基于不同物理现象（片剂的侵蚀和溶胀、药物溶解、药物反向扩散和复合物形成）之间的相互作用，对HPβCD加入对释放机制的影响进行了合理分析。在研究的第二部分，测试了含HPβCD的PEO片剂作为CAR口腔给药系统的潜力。发现片剂中加入HPβCD并未显著改变其良好的黏附性能。通过在猪离体黏膜上进行渗透实验评估了CAR口腔给药的可行性。在含HPβCD的片剂中，从PEO片剂渗透的CAR量更高，对于CAR/HPβCD冻干体系获得了最大值。我们的结果表明，当片剂用作透黏膜系统时，与在溶液中相比，水合片剂中药物溶解增强对提高给药速率的作用更为重要。
