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采用喷雾干燥技术制备并评价含二氧化硅的格列本脲-聚乙二醇化甘油酯固体分散体

Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique.

作者信息

Chauhan Bhaskar, Shimpi Shyam, Paradkar Anant

机构信息

Department of Pharmaceutics, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India.

出版信息

Eur J Pharm Sci. 2005 Oct;26(2):219-30. doi: 10.1016/j.ejps.2005.06.005.

Abstract

Solid dispersions (SDs) of glibenclamide (GBM); a poorly water-soluble drug and polyglycolized glycerides (Gelucire with the aid of silicon dioxide (Aerosil 200); as an adsorbent, were prepared by spray drying technique. SDs and spray dried GBM in comparison with pure GBM and corresponding physical mixtures (PMs) were initially characterized and then subjected to ageing study up to 3 months. Initial characterization of SDs and spray dried GBM by DSC and XRPD showed that GBM was present in its amorphous form (AGBM). Improvement in the solubility and dissolution rate was observed for all samples. DRIFT spectroscopy revealed presence of hydrogen bonding in SDs. During ageing study, almost no decrease of in vitro drug dissolution was observed, over the period of 3 months as compare with freshly prepared SDs. Slight crystallinity in SDs was observed in the DSC and XRPD studies during ageing. Moreover in vivo study in Swiss Albino mice also justified the improvement in the therapeutic efficacy of amorphous GBM in SDs over pure GBM. Thus, present study demonstrated the high potential of spray drying technique for obtaining stable free flowing SDs of poorly water-soluble drugs using polyglycolized glycerides carriers with the aid of silicon dioxide as an adsorbent.

摘要

格列本脲(GBM,一种难溶性药物)与聚乙二醇化甘油酯(Gelucire)借助二氧化硅(气相二氧化硅200,作为吸附剂)的固体分散体(SDs)通过喷雾干燥技术制备而成。将SDs和喷雾干燥的GBM与纯GBM及相应的物理混合物(PMs)进行了初步表征,然后进行了长达3个月的老化研究。通过差示扫描量热法(DSC)和X射线粉末衍射法(XRPD)对SDs和喷雾干燥的GBM进行的初步表征表明,GBM以无定形形式(AGBM)存在。所有样品的溶解度和溶出速率均有提高。漫反射红外傅里叶变换光谱(DRIFT)显示SDs中存在氢键。在老化研究期间,与新制备的SDs相比,在3个月的时间内几乎未观察到体外药物溶出度下降。在老化过程中的DSC和XRPD研究中观察到SDs中有轻微结晶。此外,在瑞士白化小鼠体内的研究也证明了SDs中无定形GBM相对于纯GBM在治疗效果上的提高。因此,本研究证明了喷雾干燥技术在借助二氧化硅作为吸附剂使用聚乙二醇化甘油酯载体获得难溶性药物稳定的自由流动SDs方面具有很高的潜力。

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