發(fā)布時(shí)間：2018-01-17 01:23

  本文關(guān)鍵詞：熱熔擠出技術(shù)制備酮咯酸氨丁三醇緩釋植入劑　出處：《廣東藥學(xué)院》2014年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 熱熔擠出 酮咯酸氨丁三醇 植入劑 緩釋 中等鎮(zhèn)痛

【摘要】：目的：建立實(shí)驗(yàn)室熱熔擠出技術(shù)酮咯酸氨丁三醇緩釋植入劑。采用熱熔擠出技術(shù)制備酮咯酸氨丁三醇緩釋植入劑并且對(duì)酮咯酸氨丁三醇植入劑的處方進(jìn)行篩選和優(yōu)化。建立酮咯酸氨丁三醇緩釋植入劑高效液相色譜測定方法。研究觀察酮咯酸氨丁三醇緩釋植入劑的體內(nèi)藥物釋放動(dòng)力學(xué)。研發(fā)中度和高度鎮(zhèn)痛并無成癮性制劑，采用熱熔擠出技術(shù)制備酮咯酸氨丁三醇緩釋植入劑，希望填補(bǔ)和滿足臨床藥物治療的需要。 方法：采用正交試驗(yàn)對(duì)植入劑的處方進(jìn)行篩選和優(yōu)化，主要考察三個(gè)因素：藥物含量，泊洛沙姆與聚乳酸的投料比以及聚乳酸的分子量�？紤]三個(gè)水平為：藥物含量分別是20%，40%和90%；泊咯沙姆與聚乳酸的投料比為0:10,1:9以及2:8；聚乳酸的分子量為5萬，16萬和54萬。采用L43的正交表進(jìn)行試驗(yàn)設(shè)計(jì)�？疾熘笜�(biāo)為外觀，載藥量和體外溶出度。進(jìn)行了酮咯酸氨丁三醇緩釋植入劑高效液相色譜測定方法學(xué)的驗(yàn)證。通過體內(nèi)外釋放度測定方法研究了酮咯酸氨丁三醇緩釋植入劑在新西蘭兔體內(nèi)藥物釋放動(dòng)力學(xué)特性。 結(jié)果：發(fā)展了一種實(shí)驗(yàn)室的簡易熱熔擠出設(shè)備，可根據(jù)試驗(yàn)制劑的不同需要通過調(diào)整模具來改變制劑的規(guī)格，具有較高的靈活性。綜合考察各種因素最后選定含藥量為20%，聚乳酸的分子量為16萬，聚乳酸和泊咯沙姆的投料比為9:1的植入劑處方。通過方法學(xué)驗(yàn)證，采用流動(dòng)相為甲醇：水：三乙胺：冰醋酸=80:19.9:0.02:0.08，色譜柱： Kromasil C18柱（250A，，4.6mm），流速：1ml/min，檢測波長319nm的色譜條件可作為酮咯酸氨丁三醇植入劑的兔體內(nèi)藥物測定方法。酮咯酸氨丁三醇的低中高日間精密度的相對(duì)標(biāo)準(zhǔn)偏差分別是8.16%，12.1%以及12.1%，分析方法的專屬性符合要求。酮咯酸氨丁三醇的日間精密度分別為7.6%，7.1%以及3.8%，變異系數(shù)均少于15%。實(shí)驗(yàn)的低，中，高濃度的相對(duì)回收率分別是106.3%，113.7%和85.3%，均符合高濃度和中濃度的相對(duì)回收率應(yīng)該在85%到115%范圍以及低濃度靠近定量限80%到120%之間要求。室溫下，樣品在3個(gè)濃度相對(duì)應(yīng)的RE%值分別為1.01%，0.96%，和1.00%,均符合穩(wěn)定性要求。制備的酮咯酸氨丁三醇植入劑的釋放時(shí)間能夠延長到18天，制劑在第7天能夠平穩(wěn)釋放，在新西蘭兔體內(nèi)的血藥濃度能夠達(dá)到0.3μg/ml。 結(jié)論：初步探討了熱熔擠出技術(shù)制備酮咯酸氨丁三醇植入劑的方法，制備了試驗(yàn)的樣品，考察了酮咯酸氨丁三醇植入劑的高效液相色譜法測定方法，進(jìn)行了酮咯酸氨丁三醇植入劑的兔體內(nèi)外釋放動(dòng)力學(xué)研究。這些實(shí)驗(yàn)工作說明，熱熔擠出技術(shù)制備酮咯酸氨丁三醇植入劑是可行的，取得的數(shù)據(jù)為該產(chǎn)品的進(jìn)一步研發(fā)提供了科學(xué)的依據(jù)。
[Abstract]:Objective:. A laboratory hot-melt extrusion technique was established for the preparation of ketoclalic acid aminobutanol sustained-release implants, and the formulation of ketoclalic acid aminobutanol implants was screened and optimized. A high performance liquid chromatography (HPLC) method was established for the determination of ketocloroic acid aminobutanol sustained-release implants. The pharmacokinetics of ketoclalic acid aminobutanol sustained-release implants in vivo was observed. Moderate and high analgesia was developed and no addictive preparations were developed. In order to fill in and meet the needs of clinical drug therapy, the sustained release implants of ketoclorobutanol were prepared by hot melt extrusion. Methods: orthogonal test was used to screen and optimize the prescription of the implant, and three main factors were investigated: drug content. The feed ratio of Poloxamer to polylactic acid and the molecular weight of polylactic acid were considered at three levels: the drug content was 20% and 90% respectively; The ratio of Poloxamer to polylactic acid was 0: 10: 1: 9 and 2: 8; The molecular weight of polylactic acid was 50,000 ~ 160,000 and 540,000. The orthogonal table of L43 was used to design the experiment. Drug loading and dissolution in vitro. The method for the determination of ketoralic acid aminobutanol sustained-release implants was validated by HPLC. In vivo and in vitro release assay was used to study the effect of ketocloroic acid aminobutanol sustained-release implants on neoxy. Pharmacokinetic characteristics of drug release in blue rabbits. Results: a simple hot-melt extrusion equipment in laboratory was developed, which can change the specification of the preparation by adjusting the mould according to the different needs of the test preparation. Comprehensive investigation of various factors finally selected the drug content is 20, the molecular weight of polylactic acid is 160,000. Polylactic acid and Poloxamer were used as implants with a ratio of 9: 1. The mobile phase consisted of methanol: water: triethylamine: glacial acetic acid 80: 19.9: 0.02: 0.08. Chromatographic column: Kromasil C18 column: 250Am / min, flow rate: 1 ml / min. The chromatographic conditions of detection wavelength at 319 nm can be used as a method for the determination of ketoclalic acid aminobutanol implants in rabbits. The relative standard deviations of low, medium and high inter-day precision of ketoclalate aminobutanol are 8.16%, respectively. In 12.1% and 12.1g, the specificity of the analytical method met the requirements. The interday precision of ketoclalic acid aminobutanol was 7.6% and 3.8%, respectively. The relative recoveries of low, medium and high concentrations were 106.3% and 85.3%, respectively. The relative recoveries of both high and medium concentrations should be in the range of 85% to 115% and the low concentrations should be in the range of 80% to 120% at room temperature. The RE% values of the samples at the three concentrations were 1. 01 and 0. 96, and 1.00% respectively. The release time of the ketocloroic acid aminobutanol implant was prolonged to 18 days, and the release time of the preparation was stable on the 7th day. In New Zealand rabbits, the concentration of the drug was 0.3 渭 g / ml. Conclusion: the method of preparing ketocloroic acid aminobutanol implant by hot melt extrusion was studied. The sample of the experiment was prepared and the HPLC method for the determination of ketoclalic acid aminobutanol implant was investigated. The release kinetics of ketoclalic acid aminobutanol implant was studied in vivo and in vitro. These experiments showed that it was feasible to prepare ketocloroic acid aminobutanol implant by hot melt extrusion. The obtained data provide a scientific basis for further research and development of the product.
【學(xué)位授予單位】：廣東藥學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R943

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