【摘要】：本文主要研究熔融制粒輔料的各種處方變量和工藝參數(shù)對(duì)藥物釋放的影響，，為山崳酸甘油酯（Compritol888ATO）用于熔融法制粒制備難溶性藥物的緩釋片劑時(shí)提供一些參考數(shù)據(jù)，從而為今后該輔料用于熱熔融制粒的產(chǎn)業(yè)化提供技術(shù)支持和應(yīng)用指導(dǎo)。根據(jù)熱熔融制粒的原理，自行設(shè)計(jì)組裝實(shí)驗(yàn)室熔融制粒設(shè)備。以卡馬西平（carbamazepine，CBZ）為模型藥物，山崳酸甘油酯為可熔融阻滯材料，考察其單獨(dú)應(yīng)用，以及與不同粘度羥丙甲纖維素（hydroxypropylmethylcellulose，HPMC）聯(lián)合應(yīng)用后，對(duì)難溶性藥物體外釋放的影響；比較濕法制粒、熔融法制粒和粉末直壓3種方法制備的緩釋片的累積釋放度差異；以f2值評(píng)價(jià)當(dāng)日制備的卡馬西平緩釋片和存放30天后的緩釋片體外釋放度是否存在差異。結(jié)果指出，單獨(dú)應(yīng)用山崳酸甘油酯時(shí)，調(diào)節(jié)乳糖與山崳酸甘油酯的比例，卡馬西平24h后累積釋放度不超過(guò)40%；山崳酸甘油酯與HPMC聯(lián)合應(yīng)用時(shí)，隨著山崳酸甘油酯的比例和HPMC粘度的降低，卡馬西平釋放速度呈增加趨勢(shì)；熔融法制粒壓片制備的緩釋片12h釋放70%，24h后釋放超過(guò)95%，濕法制粒壓片和粉末直壓壓片制備的片劑12h就釋放90%以上；與當(dāng)天制備的緩釋片相比，緩釋片存放3天、7天和30天后，f2值分別為82.72、72.87、76.00。由此可以得出，卡馬西平的釋放速度與山崳酸甘油酯在處方中占的比例呈負(fù)相關(guān)；與單獨(dú)應(yīng)用山崳酸甘油酯相比，處方中加入HPMC后更有利于卡馬西平的釋放；與濕法制粒和粉末直壓法相比，熔融法制粒壓片所產(chǎn)生的阻滯效果更強(qiáng)，在一定程度上可以用最少的輔料達(dá)到最佳的釋放效果，有利于減少制劑成本；從f2值可以看出，存放30天后的緩釋片與當(dāng)天制備出來(lái)的緩釋片相比，f2值仍大于50，說(shuō)明存放30天對(duì)片劑的釋放度影響不大。
[Abstract]:In this paper, the effects of various prescription variables and technological parameters on drug release were studied in order to provide some reference data for the preparation of sustained-release tablets of insoluble drugs by melt granulation of glyceryl behenate (Compritol888ATO). It can provide technical support and application guidance for the industrialization of hot melt granulation in the future. According to the principle of hot melt granulation, the melting granulation equipment was designed and assembled in laboratory. The effects of carbamazepine (carbamazepine,CBZ) on the release of insoluble drugs in vitro were investigated by using carbamazepine (hydroxypropylmethylcellulose,HPMC) as a model drug and glyceride as a melting block material, and combined with different viscosity of hydroxypropyl methylcellulose (hydroxypropylmethylcellulose,HPMC). The cumulative release of sustained-release tablets prepared by wet granulation, melt granulation and powder direct pressing was compared, and the in vitro release of carbamazepine sustained-release tablets prepared on the same day and stored for 30 days was evaluated by F2 value. The results showed that the cumulative release of carbamazepine was not more than 40% after 24 hours of carbamazepine when the ratio of lactose to behenate was adjusted when glyceride was used alone. The release rate of carbamazepine increased with the decrease of the ratio and viscosity of HPMC and the ratio of glyceryl behenate in combination with HPMC. The sustained-release tablets prepared by melt granulation released 70% at 12 h and over 95% after 24 h, while those prepared by wet granulation tablet and powder direct compression tablet released more than 90% at 12 h. Compared with the sustained-release tablets prepared on the same day, the f2 values of the sustained-release tablets stored for 3 days, 7 days and 30 days were 82.72, 72.87, 76.00, respectively. It can be concluded that the release rate of carbamazepine is negatively correlated with the proportion of methanolic glyceride in the prescription, and the release of carbamazepine is more favorable to carbamazepine release after the addition of HPMC than that of behenate alone. Compared with wet granulation and powder direct pressing, the blocking effect of melt granulation tablet is stronger, and the best release effect can be achieved with the least auxiliary material to a certain extent, which is helpful to reduce the preparation cost. It can be seen from the f2 value that the f2 value of the sustained-release tablets stored for 30 days is still higher than that of the sustained-release tablets prepared on the same day, indicating that 30 days storage has little effect on the release degree of the tablets.
【學(xué)位授予單位】：鄭州大學(xué)
【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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