基于固体脂质纳米粒（SLN）和纳米结构脂质载体（NLC）的尼群地平控释制剂用于局部给药的研发：体外和离体表征

Development of nitrendipine controlled release formulations based on SLN and NLC for topical delivery: in vitro and ex vivo characterization.

作者信息

Bhaskar Kesavan, Krishna Mohan Chinnala, Lingam Meka, Prabhakar Reddy Veerareddy, Venkateswarlu Vobalaboina, Madhusudan Rao Yamsani

机构信息

Novel Drug Delivery Systems Laboratory, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, India.

出版信息

Drug Dev Ind Pharm. 2008 Jul;34(7):719-25. doi: 10.1080/03639040701842485.

DOI:10.1080/03639040701842485

PMID:18612912

Abstract

The aim of the investigation is to develop solid lipid nanoparticles (SLN) and nano-structured lipid carrier (NLC) as carriers for topical delivery of nitrendipine (NDP). NDP-loaded SLN and NLC were prepared by hot homogenization technique followed by sonication, and they were characterized for particle size, zeta potential, entrapment efficiency, stability, and in vitro release profiles. Also the percutaneous permeation of NDPSLN A, NDPSLN B, and NDPNLC were investigated in abdominal rat skin using modified Franz diffusion cells. The steady state flux, permeation coefficient, and lag time of NDP were estimated over 24 h and compared with that of control (NDP solution). The particle size was analyzed by photon correlation spectroscopy (PCS) using Malvern zeta sizer, which shows that the NDPSLN A, NDPSLN B, and NDPNLC were in the range of 124-300 nm during 90 days of storage at room temperature. For all the tested formulations (NDPSLN A, NDPSLN B, and NDPNLC), the entrapment efficiency was higher than 75% after 90 days of storage. The cumulative percentage of drug release at 24 h was found to be 26.21, 30.81, and 37.52 for NDPSLN A, NDPSLN B, and NDPNLC, respectively. The results obtained from in vitro release profiles also indicated the use of these lipid nanoparticles as modified release formulations for lipophilic drug over a period of 24 h. The data obtained from in vitro release from NDPSLN A, NDPSLN B, and NDPNLC were fitted to various kinetic models. High correlation was obtained in Higuchi and Weibull model. The release pattern of drug is analyzed and found to follow Weibull and Higuchi equations. The permeation profiles were obtained for all formulations: NDPSLN A, NDPSLN B, and NDPNLC. Of all the three formulations, NDPNLC provided the greatest enhancement for NDP flux (21.485 +/- 2.82 microg/h/cm(2)), which was fourfold over control (4.881 +/- 0.96 microg/h/cm(2)). The flux obtained with NDPSLN B (16.983 +/- 2.91 microg/h/cm(2)) and NDPNLC (21.485 +/- 2.82 microg/h/cm(2)) meets the required flux (16.85 microg/h/cm(2)).

摘要

本研究的目的是开发固体脂质纳米粒（SLN）和纳米结构脂质载体（NLC）作为尼群地平（NDP）局部给药的载体。采用热均质技术结合超声处理制备了载NDP的SLN和NLC，并对其粒径、zeta电位、包封率、稳定性和体外释放曲线进行了表征。此外，还使用改良的Franz扩散池研究了NDP - SLN A、NDP - SLN B和NDP - NLC在大鼠腹部皮肤的经皮渗透。在24小时内估算了NDP的稳态通量、渗透系数和滞后时间，并与对照（NDP溶液）进行了比较。使用马尔文zeta粒度仪通过光子相关光谱法（PCS）分析粒径，结果表明在室温下储存90天期间，NDP - SLN A、NDP - SLN B和NDP - NLC的粒径在124 - 300 nm范围内。对于所有测试制剂（NDP - SLN A、NDP - SLN B和NDP - NLC），储存90天后包封率均高于75%。发现NDP - SLN A、NDP - SLN B和NDP - NLC在24小时时的药物累积释放百分比分别为26.21%、30.81%和37.52%。体外释放曲线结果还表明，这些脂质纳米粒可作为亲脂性药物在24小时内的缓释制剂。从NDP - SLN A、NDP - SLN B和NDP - NLC的体外释放获得的数据拟合到各种动力学模型。在Higuchi模型和Weibull模型中获得了高度相关性。分析药物的释放模式，发现其遵循Weibull方程和Higuchi方程。获得了所有制剂（NDP - SLN A、NDP - SLN B和NDP - NLC）的渗透曲线。在所有三种制剂中，NDP - NLC对NDP通量的增强作用最大（21.485±2.82μg/h/cm²），是对照（4.881±0.96μg/h/cm²）的四倍。NDP - SLN B（16.983±2.91μg/h/cm²）和NDP - NLC（21.485±2.82μg/h/cm²）获得的通量满足所需通量（16.85μg/h/cm²）。