Sip Szymon, Paczkowska-Walendowska Magdalena, Rosiak Natalia, Miklaszewski Andrzej, Grabańska-Martyńska Katarzyna, Samarzewska Karolina, Cielecka-Piontek Judyta
Department of Pharmacognosy, Poznan University of Medical Sciences, 4 Swiecickiego Street, 60-781 Poznan, Poland.
Institute of Materials Science and Engineering, Poznan University of Technology, Jana Pawła II 24, 61-138 Poznan, Poland.
Pharmaceuticals (Basel). 2021 Jul 23;14(8):712. doi: 10.3390/ph14080712.
Chitosan is a valued excipient due to its biocompatibility properties and increasing solubility of poorly water-soluble drugs. The research presented in this paper concerns the preparation of binary combinations of chitosan (deacetylated chitin) with carvedilol (beta-blocker) to develop a formulation with a modified carvedilol release profile. As part of the research, six physical mixtures of chitosan with carvedilol were obtained and identified by spectral (PXRD, FT-IR, and Raman), thermal (DSC), and microscopic (SEM) methods. The next stage of the research estimated the profile changes and the dissolution rate for carvedilol in the obtained drug delivery systems; the reference sample was pure carvedilol. The studies were conducted at pH = 1.2 and 6.8, simulating the gastrointestinal tract conditions. Quantitative changes of carvedilol were determined using the developed isocratic UHPLC-DAD method. Established apparent permeability coefficients proved the changes in carvedilol's permeability after introducing a drug delivery system through membranes simulating the gastrointestinal tract and skin walls. A bioadhesive potential of carvedilol-chitosan systems was confirmed using the in vitro model. The conducted research and the obtained results indicate a significant potential of using chitosan as an excipient in modern oral or epidermal drug delivery systems of carvedilol.
壳聚糖因其生物相容性以及能提高难溶性药物的溶解度，是一种很有价值的辅料。本文所呈现的研究涉及壳聚糖（脱乙酰甲壳素）与卡维地洛（β受体阻滞剂）二元组合的制备，以开发一种具有改良卡维地洛释放曲线的制剂。作为研究的一部分，制备了壳聚糖与卡维地洛的六种物理混合物，并通过光谱（粉末X射线衍射、傅里叶变换红外光谱和拉曼光谱）、热分析（差示扫描量热法）和显微镜（扫描电子显微镜）方法进行了鉴定。研究的下一阶段评估了卡维地洛在所获得的药物递送系统中的曲线变化和溶解速率；参考样品为纯卡维地洛。研究在pH = 1.2和6.8条件下进行，模拟胃肠道环境。使用所开发的等度超高效液相色谱 - 二极管阵列检测法测定了卡维地洛的定量变化。确定的表观渗透系数证明了在通过模拟胃肠道和皮肤壁的膜引入药物递送系统后，卡维地洛的渗透性发生了变化。使用体外模型证实了卡维地洛 - 壳聚糖系统的生物黏附潜力。所进行的研究和获得的结果表明，壳聚糖在现代卡维地洛口服或表皮药物递送系统中作为辅料具有巨大潜力。
