【摘要】：熔融高速攪拌法制備緩釋微丸是一個全新的制備微丸的方法,以其高效的生產(chǎn)方式,近年來受到人們越來越多的關(guān)注。以物料混合這種最簡單的方式并輔以加熱,固體粘合劑熔融成為液體,最后通過充分的混合碰撞形成微丸。關(guān)于熔融高速攪拌法制備微丸已有國外文獻(xiàn)報(bào)道,為了給生產(chǎn)提供依據(jù)、提高藥物制劑的生產(chǎn)水平,本文以自制的帶加熱套的高速攪拌制粒機(jī)對三種不同類型藥物微丸的制備工藝、處方進(jìn)行了較為全面的考察和研究。選取水溶性藥物鹽酸二甲雙胍為模型藥物,采用先制備含藥骨架丸,再包緩釋衣層的方法,最后得到緩釋微丸。對其制備工藝、處方進(jìn)行了優(yōu)化,得出了最佳的參數(shù)。粘合劑用量20%、包衣材料為硬脂酸、包衣量為15%、制丸時間25min、制丸溫度49℃℃,制備出了釋放度較好的緩釋微丸。對釋藥曲線進(jìn)行藥物動力學(xué)擬合,結(jié)果表明藥物釋放機(jī)制為non-Fickian擴(kuò)散,所以藥物的釋放是擴(kuò)散和溶蝕協(xié)同的作用機(jī)制。初步穩(wěn)定性實(shí)驗(yàn)結(jié)果表明熔融法制備的緩釋微丸在高溫、高濕、強(qiáng)光照條件下基本穩(wěn)定。選取脂溶性藥物格列齊特為模型藥,根據(jù)藥物性質(zhì),先制備空白丸芯,對其包含藥衣層后再包蠟質(zhì)衣層。對其影響因素進(jìn)行考察,最后確定乳糖用量40%,包衣材料為硬脂酸與硫酸鈣,比例為1：1,包衣量40%,攪槳轉(zhuǎn)速200rpm、攪拌時間25min、水浴溫度50℃C、升溫速率0.5℃/min。重復(fù)性實(shí)驗(yàn)結(jié)果表明以上處方、工藝可行可靠。參考前兩章的研究結(jié)果,制備了酒石酸美托洛爾緩釋微丸,通過正交設(shè)計(jì)對處方、工藝進(jìn)行優(yōu)化。最佳主要參數(shù)如下：包衣量15%、包衣比例2：1、制丸溫度48℃、制丸時間15min,通過驗(yàn)證,該法制備的酒石酸美托洛爾緩釋微丸工藝可靠,質(zhì)量可控。本次實(shí)驗(yàn)制備了三種不同藥物的緩釋微丸,均達(dá)到了預(yù)期要求。可以看出,熔融高速攪拌法制備緩釋微丸效果良好,為將來的工業(yè)化大生產(chǎn)提供了可行的參考。
[Abstract]:The preparation of sustained-release pellets by melt high speed agitation is a new method for the preparation of pellets. In recent years, more and more attention has been paid to the preparation of sustained-release pellets because of their high efficiency. The simplest way of mixing materials and heating, the solid binder melts into a liquid, and finally the pellets are formed by fully mixing and colliding. The preparation of pellets by melting high speed agitation has been reported in foreign literature. In order to provide the basis for production and improve the production level of pharmaceutical preparations, In this paper, the preparation process of three different kinds of drug pellets was investigated and studied with a self-made high speed agitating granulator with a heating sleeve. The water-soluble metformin hydrochloride was used as the model drug. The drug skeleton pill was prepared first and then the sustained-release layer was encapsulated. Finally, the sustained-release pellets were obtained. The preparation process was optimized and the optimum parameters were obtained. The coating material was stearic acid, the coating amount was 15%, the preparation time was 25 min, the preparation temperature was 49 鈩，

本文編號：2149501