Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

Abstract The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612).

摘要 本研究旨在通过溶剂浇铸法，制备以甲氧氯普胺（Metoclopramide）为模型药物的单层基质控释型透皮贴剂。研究采用不同比例的尤特奇L100（Eudragit L100）、聚乙烯吡咯烷酮K-30（Polyvinylpyrrolidone K-30）与甲基纤维素（Methylcellulose）作为基质材料，并添加聚乙二醇400（Polyethylene glycol 400）作为增塑剂。对所制备的贴剂开展多项理化性质评价，涵盖感官特性、重量差异、耐折性、厚度、溶胀指数、平整度、药物含量、溶胀指数、侵蚀率、水分含量、水蒸气透过率与吸湿率。同时采用傅里叶变换光谱（Fourier transform spectroscopy, FT-IR）、X射线衍射（X-ray diffraction, XRD）、差示扫描量热法（Differential Scanning calorimetry, DSC）与扫描电子显微镜（Scanning Electron Microscopy, SEM）对贴剂进行表征分析。扫描电子显微镜结果显示，载药贴剂表面光滑平整。以pH 7.4的磷酸盐缓冲生理盐水作为溶出介质，开展体外溶出试验。针对Z4与Z9这2个优化处方，考察天然透皮促进剂对其透皮性能的影响。分别设置5%~10%浓度的橄榄油（Olive oil）、蓖麻油（Castor oil）与桉树油（Eucalyptus oil）作为透皮促进剂，借助Franz扩散池与离体大鼠腹部皮肤开展透皮扩散试验。其中Z4-O2（添加10%橄榄油的Z4处方）展现出最优的缓释效果，其透皮通量值为310.72，接近预设目标通量值。Z4-O2的释药行为符合Higuchi释放模型（决定系数R²=0.9833），释药机制为非菲克扩散（n=0.612）。