Asmus Lutz R, Gurny Robert, Möller Michael
School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, Geneva, Switzerland.
Int J Artif Organs. 2011 Feb;34(2):238-42. doi: 10.5301/ijao.2011.6392.
The purpose of this study was to investigate the polyester hexylsubstituted poly(lactide) (hexPLA) as a possible solvent for lipophilic substances and excipient for pharmaceutical formulations. HexPLA is a biodegradable and semi-solid polymer, which allows the incorporation of active substances by simple mixing and local or systemic application to the patient through injection. The solvent behavior of hexPLA was investigated by adding the lipophilic dye Sudan III to the polymer matrix and optical monitoring of the dissolution process over time by microscopy. As a drug, the antipsychotic compound haloperidol was analyzed for its solubility in hexPLA of different molecular weights by preparing saturated solutions, and measuring the amount of incorporated drug with UV spectroscopy. The influence of the rate of solubilized to suspended drug on the burst release behavior of haloperidol from hexPLA-formulations was investigated in release tests. It is demonstrated that hexPLA dissolves both lipophilic substances, Sudan III and Haloperidol. In the molecular weight range between 2,000 g/mol and 10,000 g/mol, a lower molecular weight hexPLA resulted in a higher incorporation capacity for haloperidol. By changing from a suspension formulation of haloperidol to a solution formulation, the initial burst release established for classical PLA and PLGA systems could be minimized. HexPLA is shown to be a potent solvent and excipient for lipophilic drugs, allowing the initial burst of drug release to be modified and controlled.
本研究的目的是研究聚己基取代聚乳酸（hexPLA）作为亲脂性物质的可能溶剂和药物制剂辅料的性能。HexPLA是一种可生物降解的半固体聚合物，通过简单混合即可加入活性物质，并通过注射对患者进行局部或全身给药。通过向聚合物基质中添加亲脂性染料苏丹III，并通过显微镜对溶解过程进行光学监测，研究了hexPLA的溶剂行为。作为一种药物，通过制备饱和溶液并利用紫外光谱法测量药物的掺入量，分析了抗精神病化合物氟哌啶醇在不同分子量的hexPLA中的溶解度。在释放试验中，研究了溶解药物与悬浮药物的比例对氟哌啶醇从hexPLA制剂中突释行为的影响。结果表明，hexPLA能溶解亲脂性物质苏丹III和氟哌啶醇。在2000 g/mol至10000 g/mol的分子量范围内，较低分子量的hexPLA对氟哌啶醇具有更高的掺入能力。通过将氟哌啶醇的悬浮制剂转变为溶液制剂，可以使经典PLA和PLGA系统中建立的初始突释最小化。结果表明，HexPLA是一种有效的亲脂性药物溶剂和辅料，能够改变和控制药物释放的初始突释。
