【摘要】：鹽酸苯環(huán)壬酯(Phencynonate hydrochloride)是中樞抗膽堿藥,是新型抗暈動病藥物。目前上市的制劑僅為普通片劑,為了提高患者的順應(yīng)性,本文以鹽酸苯環(huán)壬酯為模型藥物,以陽離子交換樹脂Amberlite(?)*IRP88為載體制備了鹽酸苯環(huán)壬酯樹脂復(fù)合物口腔崩解片。 本文先對藥物的溶解度、pKa, logP等理化性質(zhì)進(jìn)行了考察。藥物分子結(jié)構(gòu)中有堿性較強(qiáng)的胺基基團(tuán),適宜采用陽離子交換樹脂Amberlite(?)IRP88制備藥物樹脂復(fù)合物。 為獲得較高的藥物利用率和適宜的載藥量,對藥液濃度、樹脂用量、反應(yīng)溫度和溶液pH進(jìn)行了考察,最終優(yōu)化出制備條件為藥物濃度C=1.0mg/mL,藥物與Amberlite(?)IRP88用量比為1:2(wt/wt),反應(yīng)溫度為室溫(25℃),介質(zhì)為純凈水。通過X-射線粉末衍射(PXRD)和差示掃描量熱法(DSC)分析表明,藥物樹脂復(fù)合物中藥物是以離子鍵形式與樹脂結(jié)合,而不是簡單的物理吸附，吸附后藥物的品型轉(zhuǎn)變?yōu)闊o定形態(tài)。對影響藥物樹脂復(fù)合物體外釋藥的影響因素進(jìn)行了研究,發(fā)現(xiàn)藥物樹脂復(fù)合物中藥物的釋放速率主要受H+強(qiáng)度、溫度和介質(zhì)中可交換離子的種類影響。介質(zhì)中H+強(qiáng)度越高,藥物釋放速率越快：升高溫度也可以提高釋藥速率；可交換離子的置換能力強(qiáng)弱順序為H+Na+K+Ca2+,表明可交換離子的分子量越大,置換能力越弱。藥物樹脂復(fù)合物中藥物的釋放屬于粒擴(kuò)散機(jī)制。 采用直接壓片法制備口腔崩解片,填充劑選擇了藥用新型輔料噴霧干燥甘露醇和甘露醇淀粉復(fù)合物,優(yōu)化出兩者最佳用量比例為1:1(mg/mg)。通過考察吸濕時間,體內(nèi)外崩解時間對三種超級崩解劑羧甲基淀粉鈉(CMS-Na)、交聯(lián)聚維酮(PVPP)和交聯(lián)羧甲基纖維素鈉(CCMC-Na)進(jìn)行篩選,得出含有20%PVPP的口腔崩解片吸濕時間和體內(nèi)外崩解時間均是最短的,確定含有20%PVPP的處方為最終處方。 通過自制的藥物樹脂復(fù)合物口腔崩解片與上市品片在四種介質(zhì)中的溶出度對比研究表明在pH1.0和pH4.5介質(zhì)中白制品的釋藥速率顯著快于上市品片,而在水中自制品基本無釋放,在人工唾液中有根少量的釋放。表明自制品在胃液環(huán)境中可以迅速釋藥而起效,在口腔中短時間內(nèi)僅有微量釋放而起到掩味作用。 采用志愿者單盲法評價藥物樹脂復(fù)合物口腔崩解片的口感,評價結(jié)果證明所制備的藥物樹脂復(fù)合物口腔崩解片,可以完全掩蓋藥物的苦味,而且無砂礫感。
[Abstract]:Phenyclic nonyl hydrochloride (Phencynonate hydrochloride) is a central anticholine drug and a new anti-motion sickness drug. In order to improve the compliance of patients, diphenyl nonyl hydrochloride was used as model drug and cation exchange resin Amberlite (?) * IRP88 as carrier to prepare oral disintegrating tablets of phenyclononyl hydrochloride resin complex. In this paper, the solubility, pKa, logP and other physicochemical properties of the drug were investigated. There are amino groups with strong alkalinity in the molecular structure of the drug, so it is suitable to use Amberlite (?) IRP88 as a cationic exchange resin to prepare the drug resin complex. In order to obtain higher drug utilization rate and suitable drug loading, the concentration of the solution, the amount of resin, the reaction temperature and the pH of the solution were investigated. The optimized preparation conditions were as follows: concentration of C _ (10) mg 路mL ~ (-1), dosage ratio of drug to Amberlite (?) IRP88 was 1:2 (wt/wt), reaction temperature was room temperature (25 鈩，

本文編號：2294256