本文選題：氨來(lái)Tk　切入點(diǎn)：諾　出處：《湖北中醫(yī)藥大學(xué)》2014年碩士論文

【摘要】：口腔潰瘍是以周期性發(fā)作為特點(diǎn)的口腔粘膜局限性損害，口瘡發(fā)作時(shí)潰瘍面有劇烈的燒灼感，疼痛難忍。局部用藥是目前治療口腔潰瘍的最有效的手段。傳統(tǒng)的劑型如口含片、含漱液等由于在病變部位滯留時(shí)間短，影響了藥效的發(fā)揮。生物粘附給藥系統(tǒng)克服了傳統(tǒng)劑型的不足，是一種較理想的口腔局部用劑型。本課題將促進(jìn)潰瘍愈合藥物氨來(lái)Tk諾（Amlexanox）和局麻藥鹽酸利多卡因組方，研制了具有良好生物粘附性的氨來(lái)Tk諾利多卡因（簡(jiǎn)稱氨利）口腔貼片和口腔膜劑。本文主要報(bào)道氨利口腔粘附制劑的處方前研究、處方和工藝優(yōu)化、質(zhì)量標(biāo)準(zhǔn)以及初步穩(wěn)定性研究。 通過(guò)單因素考察對(duì)氨利口腔貼片的處方和制備工藝進(jìn)行優(yōu)化，以崩解時(shí)間、pH、粘度、釋放度為指標(biāo)，對(duì)填充劑種類、卡波姆與甘露醇用量進(jìn)行篩選，以口感為指標(biāo)對(duì)氨利口腔貼片的矯味劑用量進(jìn)行篩選。氨利口腔貼片采用粉末直接法壓片，，按照優(yōu)化處方制備的口腔貼片硬度為60N左右,口感良好，具有明顯的緩釋和粘附特性，工藝重現(xiàn)性好。 采用正交設(shè)計(jì)法篩選氨利口腔膜劑的處方和制備工藝，以膜劑外觀（柔軟性、光滑性、成膜性、均勻性）綜合評(píng)分和膜劑的溶出度為指標(biāo)，對(duì)羧甲基纖維素鈉（CMC-Na）與聚乙烯醇（PVA17-88）的質(zhì)量比、甘油在膜漿的濃度、CMC-Na與PVA17-88的總量在膜漿中的濃度三個(gè)因素進(jìn)行優(yōu)化。優(yōu)化后的膜劑處方為0.72g氨來(lái)Tk諾，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，加蒸餾水至100g。最優(yōu)處方制備出來(lái)的氨利口腔膜劑，外觀完整，無(wú)氣泡，并具有良好的工藝重復(fù)性，膜劑體外釋藥曲線符合Higuchi方程。 本文建立了高效液相色譜法測(cè)定氨利口腔貼片和口腔膜劑的含量測(cè)定方法。氨來(lái)Tk諾在8~66μg/mL濃度范圍內(nèi)，鹽酸利多卡因在10~250μg/mL濃度范圍內(nèi)，峰面積和濃度呈現(xiàn)良好的線性關(guān)系。低、中、高三種濃度的平均回收率分別為100.1%、98.9%、100.7%，RSD為0.16%、0.25%、0.73%；利多卡因的平均回收率分別為100.1%、99.8%、99.6%，RSD為0.2%、1.3%、0.4%。 氨利口腔貼片的影響因素試驗(yàn)結(jié)果表明：高溫60℃10天對(duì)片劑的溶化性和含量無(wú)明顯影響；相對(duì)濕度92.5%下放置10天和相對(duì)濕度75%下放置10天，片劑變軟，有明顯的吸濕現(xiàn)象，但對(duì)片劑的崩解時(shí)間和含量無(wú)明顯影響；強(qiáng)光照射下10天、5天，貼片中氨來(lái)Tk諾的含量略有降低，片劑的崩解時(shí)間無(wú)明顯變化。影響因素實(shí)驗(yàn)結(jié)果表明在光照、高濕條件下，本品的質(zhì)量發(fā)生改變，提示本品宜在密閉、遮光條件下保存，并采用密封性能好的材料進(jìn)行包裝。加速試驗(yàn)采用鋁塑泡罩包裝，取供試品3批在溫度40±2℃，相對(duì)濕度75±5%條件下放置6個(gè)月，并在第1個(gè)月，2個(gè)月，3個(gè)月和6個(gè)月末取樣1次，結(jié)果表明氨利口腔貼片在加速條件下，各項(xiàng)指標(biāo)與0月比較無(wú)明顯變化，外觀、溶化性及含量均無(wú)明顯變化。
[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

本文編號(hào)：1710392