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采用尤特奇RLPO或聚乙烯吡咯烷酮共聚物(Kollidon SR)通过固体分散技术制备盐酸维拉帕米缓释剂型。

Formulation of sustained-release dosage form of verapamil hydrochloride by solid dispersion technique using Eudragit RLPO or Kollidon SR.

作者信息

Sahoo J, Murthy P N, Biswal S

机构信息

Department of Pharmaceutical Technology, Royal College of Pharmacy and Health Sciences, Andhapasara Road, Berhampur, Orissa, India.

出版信息

AAPS PharmSciTech. 2009;10(1):27-33. doi: 10.1208/s12249-008-9175-0. Epub 2009 Jan 15.

Abstract

The release of verapamil hydrochloride from tablets with Eudragit RLPO or Kollidon SR with different drug-to-polymer ratios were investigated with a view to develop twice-daily sustained-release dosage form by solid dispersion (SD) technique. The SDs containing Eudragit RLPO or Kollidon SR at drug-polymer ratios of 1:1, 1:2, and 1:3 with verapamil hydrochloride were developed using solvent evaporation technique. The physical mixtures of drug and both polymers were prepared by using simple mixing technique at the same ratio as solid dispersion. The physicochemical properties of solid dispersion were evaluated by using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The study of DSC, XRD, and FTIR could not show significant interaction between verapamil HCl and Kollidon SR or Eudragit RLPO. The solid dispersions or physical mixtures were compressed to tablets. The tablets were prepared with solid dispersions containing Eudragit RLPO or Kollidon SR, with all the official requirements of tablet dosage forms fulfilled. Tablets prepared were evaluated for the release of verapamil hydrochloride over a period of 12 h in pH 6.8 phosphate buffer using US Pharmacopoeia type II dissolution apparatus. The in vitro drug release study revealed that the tablet containing Eudragit has extended the release rate for 12 h whereas the tablet containing Kollidon SR at the same concentration has extended the release rate up to 8 h. The in vitro release profile and the mathematical models indicate that release of verapamil hydrochloride can be effectively controlled from a tablet containing solid dispersions of Eudragit RLPO. The reduction of size fraction of the SD system from 200-250 to 75-125 microm had a great effect on the drug release.

摘要

为了通过固体分散(SD)技术开发每日两次的缓释剂型,研究了盐酸维拉帕米从含有不同药物与聚合物比例的Eudragit RLPO或Kollidon SR的片剂中的释放情况。采用溶剂蒸发技术制备了药物与聚合物比例为1:1、1:2和1:3的含有Eudragit RLPO或Kollidon SR与盐酸维拉帕米的固体分散体。药物与两种聚合物的物理混合物采用简单混合技术以与固体分散体相同的比例制备。通过傅里叶变换红外光谱(FTIR)、X射线衍射(XRD)和差示扫描量热法(DSC)对固体分散体的物理化学性质进行了评估。DSC、XRD和FTIR研究未显示盐酸维拉帕米与Kollidon SR或Eudragit RLPO之间有显著相互作用。将固体分散体或物理混合物压制成片剂。制备的片剂含有Eudragit RLPO或Kollidon SR的固体分散体,满足片剂剂型的所有官方要求。使用美国药典II型溶出装置在pH 6.8的磷酸盐缓冲液中对制备的片剂进行12小时的盐酸维拉帕米释放评估。体外药物释放研究表明,含有Eudragit的片剂将释放速率延长至12小时,而含有相同浓度Kollidon SR的片剂将释放速率延长至8小时。体外释放曲线和数学模型表明,盐酸维拉帕米的释放可以从含有Eudragit RLPO固体分散体的片剂中得到有效控制。将SD系统的粒径分数从200 - 250微米减小到75 - 125微米对药物释放有很大影响。

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