Pharmaceutical Sciences School of São Paulo State University-UNESP, Araraquara-Jaú Interstate Highway, Km 1, Araraquara, SP, Brazil.
J Pharm Sci. 2010 May;99(5):2367-74. doi: 10.1002/jps.22005.
The development of a controlled-release dosage form of zidovudine (AZT) is of crucial importance, in view of the pharmacokinetics of its toxic activity. A suitable drug delivery system could increase AZT bioavailability, reducing its dose-dependent side effects. In this study, systems composed of polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol as surfactant (S), oleic acid as oil phase (O), and water (W) were developed, as possible AZT control release systems. They were characterized by polarized light microscopy (PLM), SAXS, and rheological analysis, followed by in vitro release assay. PLM and SAXS results indicated that the mixtures of S/O/W in the proportions 55/35/10 and 55/25/20 formed microemulsion (ME) systems, while 55/20/25 formed lamellar phase. The incorporation of AZT in these systems was greater than in water or oil; moreover, AZT incorporation did not significantly change the phase behavior of the mixtures. MEs behave as Newtonian fluids in flow rheological analysis and the lamellar phase as a pseudoplastic fluid. The release profile indicated that AZT could be released in a controlled manner, since an exponential pattern governs AZT diffusion, as demonstrated by the Weibull mathematical model. These systems are potential carriers for AZT and could have advantages over conventional pharmaceutical forms.
鉴于齐多夫定（AZT）的毒理活性的药代动力学特性，开发其控释剂型至关重要。合适的药物传递系统可以提高 AZT 的生物利用度，降低其剂量依赖性副作用。在这项研究中，开发了由聚氧丙烯（5）聚氧乙烯（20）鲸蜡醇作为表面活性剂（S）、油酸作为油相（O）和水（W）组成的系统，作为可能的 AZT 控释系统。通过偏光显微镜（PLM）、小角 X 射线散射（SAXS）和流变分析对其进行了表征，随后进行了体外释放试验。PLM 和 SAXS 结果表明，S/O/W 比例为 55/35/10 和 55/25/20 的混合物形成微乳液（ME）系统，而 55/20/25 形成层状相。与水或油相比，这些系统中 AZT 的掺入量更大；此外，AZT 的掺入并未显著改变混合物的相行为。ME 在流动流变分析中表现为牛顿流体，层状相表现为假塑性流体。释放曲线表明 AZT 可以以控制的方式释放，因为指数模式控制 AZT 的扩散，正如 Weibull 数学模型所证明的那样。这些系统是 AZT 的潜在载体，并且可能比传统药物形式具有优势。
