Pharmaceutics Division, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
Pharmaceutics Division, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
Int J Biol Macromol. 2018 Oct 1;117:350-361. doi: 10.1016/j.ijbiomac.2018.05.178. Epub 2018 May 25.
The main hurdle in the oral delivery of cinnarizine is its supersaturation, precipitation and re-dissolution process, influencing the oral bioavailability. To overcome this problem, an attempt was made to develop immediate and prolong buoyant tablet of cinnarizine. For this purpose, polyacrylamide-g-corn fibre gum (p-CFG) was synthesized as mucoadhesive cum swellable polymer and it was compared with already used HPMC K4M polymer. The central composite design with two numeric and one categorical factor was choosen to optimize conc. of p-CFG (X), concentration of NaHCO (X) and type of effervescent agents (X). The bioadhesive strength of p-CFG tablet was 2.4 times higher than HPMC K4M containing tablet. The formulation composition comprises of p-CFG (64.3%), sodium bi‑carbonate (12.9%) and citric acid (2%) (F) fulfilled the maximum requirement of an optimized formulation. The in-vivo animal pharmacokinetic performance revealed larger plasma half-life and reduced elimination rate as compared to CNZ suspension. Interestingly, the absorption of CNZ from optimized formulation was 3 times enhanced than from CNZ suspension. Overall, the enhancement in the oral bioavailability of CNZ was evident that is due to its prolonged gastric residence time. Furthermore, the swelling associated floating followed by mucoadhesive nature of tablet was observed by X-ray imaging studies.
肉桂嗪经口给药的主要障碍是其过饱和、沉淀和再溶解过程，这影响了口服生物利用度。为了克服这个问题，我们试图开发肉桂嗪即刻和持续漂浮片剂。为此，合成了聚丙烯酰胺-g-玉米纤维胶（p-CFG）作为具有粘膜粘附性和溶胀性的聚合物，并将其与已使用的 HPMC K4M 聚合物进行了比较。选择了具有两个数值和一个分类因子的中心复合设计来优化 p-CFG（X）的浓度、NaHCO（X）的浓度和泡腾剂的类型（X）。p-CFG 片剂的生物粘附强度比含有 HPMC K4M 的片剂高 2.4 倍。配方组成包括 p-CFG（64.3%）、碳酸氢钠（12.9%）和柠檬酸（2%）（F）满足了优化配方的最大要求。体内动物药代动力学研究表明，与肉桂嗪混悬剂相比，肉桂嗪的血浆半衰期更长，消除率更低。有趣的是，与肉桂嗪混悬剂相比，优化配方中肉桂嗪的吸收增加了 3 倍。总的来说，肉桂嗪的口服生物利用度得到了明显提高，这是由于其胃滞留时间延长。此外，通过 X 射线成像研究观察到了与片剂的膨胀相关的漂浮和粘膜粘附特性。
