難溶性藥物體外溶出評(píng)價(jià)及溶出度方法的建立
發(fā)布時(shí)間：2018-12-21 15:35
【摘要】：溶出度是指在規(guī)定條件下藥物活性成分從片劑、膠囊劑或顆粒劑等固體口服制劑中溶出的速率和程度。當(dāng)前,溶出度的應(yīng)用日趨廣泛,它可以用于處方、制劑工藝和劑型的評(píng)價(jià)和篩選,固體制劑的質(zhì)量評(píng)價(jià),根據(jù)溶出度結(jié)果并結(jié)合體內(nèi)外相關(guān)性,預(yù)測(cè)藥物的體內(nèi)生物利用度等,由此可見,溶出度試驗(yàn)現(xiàn)已成為藥品質(zhì)量控制的重要項(xiàng)目之一。然而,現(xiàn)行藥品特別是難溶性藥物的質(zhì)量標(biāo)準(zhǔn)中的溶出度方法,其溶出度結(jié)果與體內(nèi)生物利用度是否相關(guān)尚存爭(zhēng)議,例如為了使藥物能夠完全溶出,采用過(guò)于劇烈的溶出條件,與胃腸道生理環(huán)境嚴(yán)重不符。由此可能導(dǎo)致不同企業(yè)的同種藥物的臨床療效差異較大。因此,探索建立既能反映藥物內(nèi)在質(zhì)量又能體現(xiàn)其體內(nèi)生物活性的溶出度方法,對(duì)嚴(yán)格控制藥品質(zhì)量,確保藥品臨床使用的有效性和安全性至關(guān)重要。 本課題通過(guò)考察不同類型的難溶性藥物替米沙坦(弱酸性)、卡馬西平(中性)和卡維地洛(弱堿性)的溶解度和表觀油水分配系數(shù)等理化性質(zhì),對(duì)三種藥物的溶出條件從溶出介質(zhì)、溶出體積和轉(zhuǎn)速等方面進(jìn)行優(yōu)化,建立更接近胃腸道內(nèi)環(huán)境的溶出條件,并對(duì)不同企業(yè)生產(chǎn)的樣品分別進(jìn)行溶出行為考察的同時(shí),與日本橙皮書中的溶出曲線做比對(duì)分析。實(shí)驗(yàn)表明,優(yōu)化后的溶出度方法有較好的區(qū)分力,能更客觀地評(píng)價(jià)藥品的質(zhì)量,且溶出條件與生理環(huán)境相似度高,具有良好的體內(nèi)外相關(guān)性。此外,本課題利用激光共聚焦顯微拉曼光譜儀對(duì)三種藥物的不同企業(yè)樣品進(jìn)行拉曼圖譜測(cè)定,結(jié)果表明,卡馬西平片和卡維地洛片不同樣品問(wèn)的溶出差異與晶型無(wú)關(guān),替米沙坦片存在三種拉曼圖譜,相應(yīng)的溶出情況也不同,主要是由不同的處方或生產(chǎn)工藝造成的。 本課題對(duì)不同類型難溶性藥物的溶出條件進(jìn)行研究,并根據(jù)優(yōu)選條件比較分析不同工藝和處方制劑的溶出曲線,為研究和建立合理的溶出度方法提供策略和指導(dǎo),并為進(jìn)一步研究溶出度的體內(nèi)外相關(guān)性提供有意義的參考。
[Abstract]:Dissolution rate is the rate and extent of dissolution of active components from tablets, capsules or granules. At present, dissolution has been used more and more widely. It can be used in the evaluation and screening of prescriptions, preparation processes and dosage forms, the quality evaluation of solid preparations, and the prediction of bioavailability of drugs in vivo and in vivo according to the dissolution results and the correlation in vivo and in vitro. Thus, dissolution test has become one of the important items of drug quality control. However, whether the dissolution method in the current quality standards for drugs, especially insoluble drugs, is relevant to bioavailability in vivo, for example, in order to allow the drug to be completely dissolved, is subject to excessive dissolution conditions, It is seriously incompatible with the physiological environment of the gastrointestinal tract. This may lead to greater differences in the clinical efficacy of the same drug in different enterprises. Therefore, it is very important to establish a dissolution method which can reflect both the intrinsic quality and the biological activity of drugs, which is very important to strictly control the quality of drugs and ensure the effectiveness and safety of clinical use of drugs. The physical and chemical properties of different insoluble drugs, such as telmisartan (weak acid), carbamazepine (neutral) and carvedilol (weak alkalinity), were investigated. The dissolution conditions of the three drugs were optimized from the aspects of dissolution medium, volume and speed of dissolution, so as to establish the dissolution conditions closer to the environment in the gastrointestinal tract. At the same time, the samples produced by different enterprises were investigated respectively. Compare and analyze the dissolution curve in Japanese orange peel book. The experimental results show that the optimized dissolution method has better discriminating power and can objectively evaluate the quality of drugs, and the dissolution conditions have high similarity with the physiological environment and have good in vitro and in vivo correlation. In addition, the Raman spectra of different samples of three drugs were determined by laser confocal microscopy Raman spectrometer. The results showed that the dissolution of carbamazepine tablets and carvedilol tablets was not related to the crystal type. There are three kinds of Raman patterns in telmisartan tablets, and the dissolution conditions are different, mainly caused by different prescriptions or production processes. In this paper, the dissolution conditions of different insoluble drugs were studied, and the dissolution curves of different processes and prescriptions were compared and analyzed according to the optimal conditions, which provided strategies and guidance for the study and establishment of reasonable dissolution methods. It also provides a useful reference for further study on in vitro and in vivo correlation of dissolution.
【學(xué)位授予單位】：浙江工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R917
本文編號(hào)：2389103
[Abstract]:Dissolution rate is the rate and extent of dissolution of active components from tablets, capsules or granules. At present, dissolution has been used more and more widely. It can be used in the evaluation and screening of prescriptions, preparation processes and dosage forms, the quality evaluation of solid preparations, and the prediction of bioavailability of drugs in vivo and in vivo according to the dissolution results and the correlation in vivo and in vitro. Thus, dissolution test has become one of the important items of drug quality control. However, whether the dissolution method in the current quality standards for drugs, especially insoluble drugs, is relevant to bioavailability in vivo, for example, in order to allow the drug to be completely dissolved, is subject to excessive dissolution conditions, It is seriously incompatible with the physiological environment of the gastrointestinal tract. This may lead to greater differences in the clinical efficacy of the same drug in different enterprises. Therefore, it is very important to establish a dissolution method which can reflect both the intrinsic quality and the biological activity of drugs, which is very important to strictly control the quality of drugs and ensure the effectiveness and safety of clinical use of drugs. The physical and chemical properties of different insoluble drugs, such as telmisartan (weak acid), carbamazepine (neutral) and carvedilol (weak alkalinity), were investigated. The dissolution conditions of the three drugs were optimized from the aspects of dissolution medium, volume and speed of dissolution, so as to establish the dissolution conditions closer to the environment in the gastrointestinal tract. At the same time, the samples produced by different enterprises were investigated respectively. Compare and analyze the dissolution curve in Japanese orange peel book. The experimental results show that the optimized dissolution method has better discriminating power and can objectively evaluate the quality of drugs, and the dissolution conditions have high similarity with the physiological environment and have good in vitro and in vivo correlation. In addition, the Raman spectra of different samples of three drugs were determined by laser confocal microscopy Raman spectrometer. The results showed that the dissolution of carbamazepine tablets and carvedilol tablets was not related to the crystal type. There are three kinds of Raman patterns in telmisartan tablets, and the dissolution conditions are different, mainly caused by different prescriptions or production processes. In this paper, the dissolution conditions of different insoluble drugs were studied, and the dissolution curves of different processes and prescriptions were compared and analyzed according to the optimal conditions, which provided strategies and guidance for the study and establishment of reasonable dissolution methods. It also provides a useful reference for further study on in vitro and in vivo correlation of dissolution.
【學(xué)位授予單位】：浙江工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R917
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 紀(jì)洪萍;;改善固體制劑溶出度的方法探討[J];黑龍江科技信息;2012年05期
2 吳君華;柳晨;裴元英;;布地奈德劑型的研究進(jìn)展及其臨床應(yīng)用[J];中國(guó)臨床藥學(xué)雜志;2007年01期
，本文編號(hào)：2389103
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