基于牛油果脂脂质基质的氢氯噻嗪固体脂质微粒的制备与表征

Formulation and characterization of hydrochlorothiazide solid lipid microparticles based on lipid matrices of Irvingia fat.

作者信息

Agubata Chukwuma O, Chime Salome A, Kenechukwu Franklin C, Nzekwe Ifeanyi T, Onunkwo Godswill C

机构信息

Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka, Enugu, Nigeria.

Department of Pharmaceutics, University of Nigeria, Nsukka, Enugu, Nigeria.

出版信息

Int J Pharm Investig. 2014 Oct;4(4):189-94. doi: 10.4103/2230-973X.143120.

DOI:10.4103/2230-973X.143120

PMID:25426440

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4241624/

Abstract

INTRODUCTION

The purpose of this study was to improve the solubilization, bioavailability, and permeability of hydrochlorothiazide (HCTZ) by the formulation and characterization of HCTZ solid lipid microparticles (SLMs) based on fat derived from Irvingia gabonensis var. excelsa (Irvingia wombolu) and Phospholipon(®)90G (P90G).

MATERIALS AND METHODS

Irvingia fat was extracted from the nut of I. gabonensis var. excelsa using petroleum ether (40-60°C). HCTZ loaded SLM were formulated using hot homogenization method with 5% w/w Irvingia fat/P90G at each of 1:0, 9:1, 4:1, and 3:1 ratios, 1% w/w HCTZ, 1.5% w/w Labrasol(®) surfactant and distilled water. Subsequently, particle size analysis, pH, syringeability, drug encapsulation efficiency (EE%), yield, freeze-thaw cycle test, drug release, diffusion, and kinetics were evaluated.

RESULTS

The SLM dispersions showed a particle size range of 10.15 ± 2.36 to 13.50 ± 6.88 μm and pH of 5.6-6.4 while dispersions containing 3:1 Irvingia fat/P90G passed through most of the needles (18G, 21G, and 22G) after syringeability studies. A single freeze-thaw cycle caused loss of physical integrity. The EE% of the SLMs were ≥80%, with high yield. The highest drug release and diffusion was observed with SLMs prepared with 3:1 Irvingia fat-P90G mixture (HDP3) and Higuchi model best described the kinetics of the HCTZ release by Fickian diffusion.

CONCLUSION

The release and permeability of HCTZ was improved by its incorporation into Irvingia fat and P90G (3:1) as SLMs.

摘要

引言

本研究的目的是通过基于加蓬油桃木（Irvingia gabonensis var. excelsa，即Irvingia wombolu）脂肪和磷脂酰胆碱（Phospholipon®90G，简称P90G）制备和表征氢氯噻嗪（HCTZ）固体脂质微粒（SLMs），来提高其溶解性、生物利用度和渗透性。

材料与方法

使用石油醚（40 - 60°C）从加蓬油桃木变种的坚果中提取油桃木脂肪。采用热均质法，以1:0、9:1、4:1和3:1的比例分别使用5% w/w的油桃木脂肪/P90G、1% w/w的HCTZ、1.5% w/w的Labrasol®表面活性剂和蒸馏水来制备负载HCTZ的SLMs。随后，对粒径分析、pH值、可注射性、药物包封率（EE%）、产率、冻融循环试验、药物释放、扩散和动力学进行了评估。

结果

SLMs分散体的粒径范围为10.15 ± 2.36至13.50 ± 6.88μm，pH值为5.6 - 6.4；在可注射性研究后，含有3:1油桃木脂肪/P90G的分散体能够通过大多数针头（18G、21G和22G）。单次冻融循环导致物理完整性丧失。SLMs的EE%≥80%，产率较高。用3:1油桃木脂肪 - P90G混合物（HDP3）制备的SLMs观察到最高的药物释放和扩散，Higuchi模型最能描述HCTZ通过菲克扩散的释放动力学。