Gao Z H, Shukla A J, Johnson J R, Crowley W R
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Pharm Res. 1995 Jun;12(6):857-63. doi: 10.1023/a:1016209020160.
The purpose of this study was to investigate the effects of formulation factors including varying wax concentration, drug loading and drug particle size, on drug release characteristics from both pure oil and gel formulations prepared with a combination of derivatized vegetable oil (Labrafil 1944 CS) and glyceryl palmitostearate (Precirol ATO 5), using levonorgestrel as a model drug.
The effects of varying drug loadings, different drug particle sizes, and wax (Precirol) concentrations on in-vitro drug release rates were evaluated, and the mechanisms of drug release from the gels were determined.
Zero-order drug release rates from the 10% Precirol gel formulations containing 0.25, 0.50 and 2.00% w/v drug loadings were lower than those observed for oil formulations containing identical drug loadings. Higher zero-order release rates were observed from formulations containing smaller drug particles suspended in both oil and gel formulations. The mechanism of drug release from gels containing less than 0.25% w/w drug was diffusion-controlled. Increasing the wax concentrations in the gels from 5% w/w to 20% w/w significantly decreased the diffusivity of the drug through the gel formulations and markedly increased the force required to inject the gels from two different sizes of needles.
This study shows how modification of the physicochemical properties of the gel formulations by changing the drug particle size, wax concentration and drug loading, affects drug release characteristics from the system.
本研究旨在考察包括蜡浓度变化、载药量和药物粒径等制剂因素对使用左炔诺孕酮作为模型药物，由衍生植物油（Labrafil 1944 CS）和甘油棕榈硬脂酸酯（Precirol ATO 5）组合制备的纯油制剂和凝胶制剂中药物释放特性的影响。
评估了不同载药量、不同药物粒径和蜡（Precirol）浓度对体外药物释放速率的影响，并确定了凝胶中药物的释放机制。
含0.25%、0.50%和2.00%（w/v）载药量的10% Precirol凝胶制剂的零级药物释放速率低于含相同载药量的油制剂。在油制剂和凝胶制剂中，含较小药物颗粒的制剂观察到更高的零级释放速率。含药量低于0.25%（w/w）凝胶的药物释放机制为扩散控制。将凝胶中的蜡浓度从5%（w/w）增加到20%（w/w）显著降低了药物在凝胶制剂中的扩散率，并显著增加了从两种不同尺寸针头注射凝胶所需的力。
本研究表明，通过改变药物粒径、蜡浓度和载药量来改变凝胶制剂的物理化学性质，如何影响系统中的药物释放特性。
