氨利口腔粘附给药系统的研究

发布时间：2018-04-04 14:39

  本文选题：氨来Tk　切入点：诺　出处：《湖北中医药大学》2014年硕士论文

【摘要】：口腔溃疡是以周期性发作为特点的口腔粘膜局限性损害，口疮发作时溃疡面有剧烈的烧灼感，疼痛难忍。局部用药是目前治疗口腔溃疡的最有效的手段。传统的剂型如口含片、含漱液等由于在病变部位滞留时间短，影响了药效的发挥。生物粘附给药系统克服了传统剂型的不足，是一种较理想的口腔局部用剂型。本课题将促进溃疡愈合药物氨来Tk诺（Amlexanox）和局麻药盐酸利多卡因组方，研制了具有良好生物粘附性的氨来Tk诺利多卡因（简称氨利）口腔贴片和口腔膜剂。本文主要报道氨利口腔粘附制剂的处方前研究、处方和工艺优化、质量标准以及初步稳定性研究。 通过单因素考察对氨利口腔贴片的处方和制备工艺进行优化，以崩解时间、pH、粘度、释放度为指标，对填充剂种类、卡波姆与甘露醇用量进行筛选，以口感为指标对氨利口腔贴片的矫味剂用量进行筛选。氨利口腔贴片采用粉末直接法压片，，按照优化处方制备的口腔贴片硬度为60N左右,口感良好，具有明显的缓释和粘附特性，工艺重现性好。 采用正交设计法筛选氨利口腔膜剂的处方和制备工艺，以膜剂外观（柔软性、光滑性、成膜性、均匀性）综合评分和膜剂的溶出度为指标，对羧甲基纤维素钠（CMC-Na）与聚乙烯醇（PVA17-88）的质量比、甘油在膜浆的浓度、CMC-Na与PVA17-88的总量在膜浆中的浓度三个因素进行优化。优化后的膜剂处方为0.72g氨来Tk诺，1.8g利多卡因，2.0gCMC-Na，3.0gPVA-1788，2.5mL甘油，0.05g阿斯巴甜，0.05g薄荷粉，加蒸馏水至100g。最优处方制备出来的氨利口腔膜剂，外观完整，无气泡，并具有良好的工艺重复性，膜剂体外释药曲线符合Higuchi方程。 本文建立了高效液相色谱法测定氨利口腔贴片和口腔膜剂的含量测定方法。氨来Tk诺在8~66μg/mL浓度范围内，盐酸利多卡因在10~250μg/mL浓度范围内，峰面积和浓度呈现良好的线性关系。低、中、高三种浓度的平均回收率分别为100.1%、98.9%、100.7%，RSD为0.16%、0.25%、0.73%；利多卡因的平均回收率分别为100.1%、99.8%、99.6%，RSD为0.2%、1.3%、0.4%。 氨利口腔贴片的影响因素试验结果表明：高温60℃10天对片剂的溶化性和含量无明显影响；相对湿度92.5%下放置10天和相对湿度75%下放置10天，片剂变软，有明显的吸湿现象，但对片剂的崩解时间和含量无明显影响；强光照射下10天、5天，贴片中氨来Tk诺的含量略有降低，片剂的崩解时间无明显变化。影响因素实验结果表明在光照、高湿条件下，本品的质量发生改变，提示本品宜在密闭、遮光条件下保存，并采用密封性能好的材料进行包装。加速试验采用铝塑泡罩包装，取供试品3批在温度40±2℃，相对湿度75±5%条件下放置6个月，并在第1个月，2个月，3个月和6个月末取样1次，结果表明氨利口腔贴片在加速条件下，各项指标与0月比较无明显变化，外观、溶化性及含量均无明显变化。
[Abstract]:Oral ulcer is characterized by periodic localized lesions of oral mucosa.Local medication is the most effective method for the treatment of oral ulcer.Traditional formulations, such as oral buccal tablets and gargle, affected the effectiveness of the drug because of their short retention time in the diseased areas.Bioadhesive drug delivery system overcomes the shortcomings of traditional dosage forms and is an ideal oral local dosage form.This paper mainly reports the preprescription study, prescription and process optimization, quality standard and preliminary stability study of ambroxide oral adhesive preparation.The formulation and preparation process of ambroxide oral patch were optimized by single factor investigation. Taking the disintegrating time pH, viscosity and release degree as the index, the kinds of fillers, the amount of carbomer and mannitol were selected.The dosage of ambroxide oral patch was screened with taste index.Amini oral patch was prepared by direct powder pressing. The hardness of the patch was about 60 N, which had good taste, obvious sustained release and adhesion, and good reproducibility.The formulation and preparation process of ambroxide oral membrane were selected by orthogonal design. The comprehensive score of membrane appearance (softness, smoothness, film-forming, uniformity) and dissolution of the membrane were taken as the index.The mass ratio of CMC-Na and PVA17-88) and the concentration of glycerol in membrane pulp were optimized.A high performance liquid chromatography (HPLC) method for the determination of ambroxide oral patch and oral membrane was established.There was a good linear relationship between the peak area and the concentration of lidocaine hydrochloride and lidocaine hydrochloride in the range of 866 渭 g/mL and 10 渭 g/mL, respectively.The experimental results showed that the dissolution and content of the tablets were not affected by high temperature of 60 鈩

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