Design and optimization of kollicoat ® IR based mucoadhesive buccal film for co-delivery of rizatriptan benzoate and propranolol hydrochloride.
Design and optimization of kollicoat ® IR based mucoadhesive buccal film for co-delivery of rizatriptan benzoate and propranolol hydrochloride.
复制标题
设计和优化基于 kollicoat ® IR 的粘膜粘附颊膜，用于苯甲酸利扎曲普坦和盐酸普萘洛尔的共同递送。
DOI：
10.1016/j.msec.2018.12.036
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Soheil Boddohi
中科院分区：
文献类型：
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作者：
S. Salehi;Soheil Boddohi
本工作旨在开发一种用于苯甲酸利扎曲普坦（RB）和盐酸普萘洛尔（PRH）潜在联合给药的粘膜粘附口腔膜剂。使用Kollicoat ® IR、聚环氧乙烷（PEO）、羟丙基甲基纤维素（HPMC K4 M）、甘油、甜叶菊和芦荟凝胶粉末（AVgel粉末）通过溶剂浇铸法制备膜。为了表征和优化制剂，使用具有中心复合设计（CCD）的Design-Expert软件。选择的自变量是Kollicoat ® IR、PEO、甘油和AVgel粉末的浓度。五个选定的因变量是体外崩解时间，耐折性，溶胀比，和体外药物释放。选择具有50 mg PRH、25 mg RB、5 mg甜叶菊、63 mg HPMC K4 M、100 mg Kollicoat ® IR、66.33 mg PEO、0.22 ml甘油和0.8 mg AVgel粉末的膜作为优化制剂。采用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）和差示扫描量热仪（DSC）对优化后的薄膜进行表征，以评价薄膜的形貌、化学结构和物理性能。采用Santam仪器测试了优化膜的力学性能。以大鼠口腔粘膜为模型膜，采用Franz扩散池研究离体渗透。优化的膜结合AVgel粉末作为一种天然的渗透促进剂可以通过大鼠颊粘膜的PRH和96.11%的RB超过100分钟，并显示没有颊粘膜损伤后的组织病理学评价。总的来说，优化的薄膜可能是有效治疗偏头痛的潜在候选者。
This work aimed to develop a mucoadhesive buccal film for potential co-delivery of rizatriptan benzoate (RB) and propranolol hydrochloride (PRH). Kollicoat ® IR, polyethylene oxide (PEO), hydroxypropyl methylcellulose (HPMC K4M), glycerol, stevia, andAloe veragel powder (AVgel powder) were used to prepare film by solvent casting method. In order to characterize and optimize formulations, Design-Expert software with central composite design (CCD) was used. The selected independent variables were concentrations of Kollicoat ® IR, PEO, glycerol, and AVgel powder. Five selected dependent variables were in vitro disintegration time, folding endurance, swelling ratio, and in vitro drugs release. Film with 50 mg PRH, 25 mg RB, 5 mg stevia, 63 mg HPMC K4M, 100 mg Kollicoat ® IR, 66.33 mg PEO, 0.22 ml glycerol, and 0.8 mg AVgel powder was selected as optimized formulation. The optimized film was characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) to evaluate morphology, chemical structure, and physical properties of the film. The mechanical properties of optimized film were measured by Santam instrument. Ex vivo permeation were studied by Franz diffusion cell, while rat buccal mucosa was used as a model membrane. The optimized film with incorporation of AVgel powder as a natural permeation enhancer could transport 73.22% of PRH and 96.11% of RB over 100 min through rat buccal mucosa and showed no buccal mucosal damage after histopathological evaluation. Overall, the optimized film could be a potential candidate for the effective treatment of migraine.