盐酸替扎尼定-美洛昔康负载黏膜粘附颊膜的研制:体外和体内评价。

Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation.

机构信息

Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan.

出版信息

PLoS One. 2018 Mar 22;13(3):e0194410. doi: 10.1371/journal.pone.0194410. eCollection 2018.

Abstract

The purpose of the study was to develop Tizanidine HCl (TZN) and Meloxicam (MLX) loaded bilayer mucoadhesive films intended for buccal administration, aiming to enhance the bioavailability. Bilayer films were prepared by solvent evaporation technique selecting arabinoxylan (ARX) as a sustained release (SR) layer forming polymer and hydroxypropyl methylcellulose (HPMC) E-15 as an immediate release (IR) layer-forming polymer. Prepared films were subjected to in-vitro drug release, surface morphology, mechanical strength, compatibility of the ingredients, drug contents, ex-vivo mucoadhesion strength and drug permeation. Crossover study design was applied to study the in-vivo pharmacokinetics by using albino rabbits. Various pharmacokinetic parameters including AUC, Cmax, tmax and t1/2 of both drugs loaded in films were compared with standard solution/dispersion administered to the rabbits at the dose of 1mg/kg. The results unveiled instant release and permeation of MLX from IR layer, while good controlled release and permeation characteristics of TZN from SR films over 8 h. films were of uniform thickness with smooth surface and satisfactory mechanical strength. Mucoadhesion strength was sufficient to provide suitable contact time with mucosal membrane. The pharmacokinetic study exhibited prompt absorption of MLX with better AUC 0-t (6655.64 ng/mlh vs 6538.99 ng/mlh) and Cmax (436.98 ng/ml vs 411.33 ng/ml) from oral dispersion. Similarly buccal films has shown enhanced half-life (9.91hr vs 2.51 hr), AUC 0-t (1043.4 ng/mlh vs 149.1 ng/mlh) and Cmax (91.92 ng/ml vs 42.29 ng/ml) from oral solution. A statistical investigation disclosed a significantly improved pharmacokinetics of TZN and MLX after their absorption across buccal route following administration of buccal film (p<0.05). ARX proved expedient and bilayer buccal films as a drug delivery system ascertained the dual effect of providing instant release of one active agent and persistent release of another one with improved pharmacokinetics.

摘要

本研究旨在开发替扎尼定盐酸盐(TZN)和美洛昔康(MLX)双层粘膜粘附片,用于口腔给药,旨在提高生物利用度。双层膜采用溶剂蒸发技术制备,选择阿拉伯木聚糖(ARX)作为缓释(SR)层形成聚合物,羟丙基甲基纤维素(HPMC)E-15 作为速释(IR)层形成聚合物。制备的膜进行体外药物释放、表面形态、机械强度、成分相容性、药物含量、离体粘膜粘附强度和药物渗透。采用交叉研究设计,用白化兔研究体内药代动力学。将两种药物在薄膜中的 AUC、Cmax、tmax 和 t1/2 等各种药代动力学参数与以 1mg/kg 剂量给兔子施用的标准溶液/分散体进行比较。结果表明,IR 层中 MLX 立即释放和渗透,而 SR 膜中 TZN 具有良好的控释和 8 小时内渗透特性。薄膜均匀厚度、表面光滑、机械强度良好。粘膜粘附强度足以提供与粘膜的适当接触时间。药代动力学研究表明,口服分散剂中 MLX 吸收迅速,AUC0-t(6655.64ng/mlh 比 6538.99ng/mlh)和 Cmax(436.98ng/ml 比 411.33ng/ml)更好。同样,口腔膜显示出增强的半衰期(9.91hr 比 2.51hr)、AUC0-t(1043.4ng/mlh 比 149.1ng/mlh)和 Cmax(91.92ng/ml 比 42.29ng/ml)从口服溶液。统计学研究表明,口腔膜给药后,TZN 和 MLX 经口腔吸收的药代动力学有显著改善(p<0.05)。ARX 被证明是一种方便的药物,双层口腔膜作为一种药物传递系统,确定了提供一种活性剂的即时释放和另一种活性剂的持续释放的双重效果,同时改善了药代动力学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70fe/5864138/22409a0c177b/pone.0194410.g001.jpg

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