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采用多相乳化技术,以卡拉胶-刺槐豆胶混合物进行微囊化用于药物缓释。

Microencapsulation with carrageenan-locust bean gum mixture in a multiphase emulsification technique for sustained drug release.

作者信息

Suzuki S, Lim J K

机构信息

Department of Ophthalmology, School of Medicine, West Virginia University, Morgantown 26505.

出版信息

J Microencapsul. 1994 Mar-Apr;11(2):197-203. doi: 10.3109/02652049409040451.

DOI:10.3109/02652049409040451
PMID:8006767
Abstract

A multiphase emulsification technique was modified in this process of micro-encapsulating gentamicin sulphate, thus avoiding the necessity for a surfactant in preparing the secondary emulsion for a W/O/W emulsion. Various proportions of iota-carrageenan (i-C) and locus bean gum (LBG) were investigated for the W/O/W emulsion after forming the primary W/O emulsion with sorbitan trioleate, Span 85. Upon removal of the oil phase (chloroform) from the W/O/W emulsion by heating (60-65 degrees C), microcapsules or 'W/W' particles containing drug dissolved in sodium hyaluronate were spontaneously formed. These were dispersed in a solution of a mixture of 5-10 per cent w/v polyvinyl alcohol, PVA (average MW 50,000-106,000; 98 per cent hydrolysed) and 3 per cent v/v polyethylene glycol 200 (PEG 200), and dried to form the hydrogel film casts. Our in vitro experiments in isotonic phosphate buffer solution (pH 7.4) at 37 degrees C, showed that the release of gentamicin sulphate was dependent on concentration of LBG, and concentration or molecular weight of PVA. With the exception of PVA hydrogel matrix preparations containing 20 per cent w/v LBG, all other formulations showed a significant initial 'burst' release of drug within 6 h. The drug-containing microcapsules in the PVA hydrogel film with 20 per cent w/v LBG, exhibited an almost zero-order release of drug up to 140 h. It is postulated that an effective barrier or high-density membrane enveloping the microcapsules was formed between i-C and LBG because of their unique molecular configurations. This phenomenon, together with the possible adsorption of i-C molecules at the transient oil and outer aqueous phase interface, presumably eliminated the need for a permanent oil phase and/or an O/W surfactant normally required for preparing W/O/W emulsions.

摘要

在硫酸庆大霉素微囊化过程中对多相乳化技术进行了改进,从而避免了在制备W/O/W乳液的二次乳液时使用表面活性剂。在用脱水山梨醇三油酸酯(Span 85)形成初级W/O乳液后,研究了不同比例的iota-卡拉胶(i-C)和刺槐豆胶(LBG)用于W/O/W乳液的情况。通过加热(60-65摄氏度)从W/O/W乳液中除去油相(氯仿)后,自发形成了含有溶解在透明质酸钠中的药物的微囊或“W/W”颗粒。将这些分散在5-10% w/v聚乙烯醇(PVA,平均分子量50,000-106,000;水解度98%)和3% v/v聚乙二醇200(PEG 200)的混合溶液中,并干燥以形成水凝胶膜铸型。我们在37摄氏度的等渗磷酸盐缓冲溶液(pH 7.4)中进行的体外实验表明,硫酸庆大霉素的释放取决于LBG的浓度以及PVA的浓度或分子量。除了含有20% w/v LBG的PVA水凝胶基质制剂外,所有其他制剂在6小时内都显示出药物的显著初始“突释”。含有20% w/v LBG的PVA水凝胶膜中的含药微囊在长达140小时内表现出几乎零级的药物释放。据推测,由于i-C和LBG独特的分子构型,在它们之间形成了包围微囊的有效屏障或高密度膜。这种现象,连同i-C分子可能在瞬时油相和外部水相界面处的吸附,大概消除了制备W/O/W乳液通常所需的永久性油相和/或O/W表面活性剂。

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