Malaterre Vincent, Ogorka Joerg, Loggia Nicoletta, Gurny Robert
Novartis Pharma AG, Technical R&D, Basel, Switzerland.
Int J Pharm. 2009 Jul 6;376(1-2):56-62. doi: 10.1016/j.ijpharm.2009.04.015. Epub 2009 Apr 19.
Despite more than 30 years of clinical use, only few studies have been published reporting on the release mechanism underlying the drug delivery from push-pull osmotic pumps (PPOP). The aim of this study is to understand which factors have an effect on the drug delivery for modelling the drug release and to develop a mathematical model predictive of the drug release kinetics. The influence of the drug property was tested on two model drugs, isradipine (ISR) and chlorpheniramine (CPA) which are respectively practically insoluble and freely soluble. Results show that, regardless of the drug properties which do not significantly affect the drug delivery, the release kinetics is mainly controlled by four factors, (i) the PEG proportion in the membrane, (ii) the tablet surface area, (iii) the osmotic agent proportion and (iv) the drug layer polymer grade. The influence of each key formulation factors on the release mechanism was investigated defining their applicability range. A mathematical approach was developed to predict the drug delivery kinetics varying the PPOP controlling factors and helps to more efficiently design PPOP.
尽管推挽式渗透泵（PPOP）在临床上已使用了30多年，但仅有少数研究报道了其药物释放的潜在机制。本研究的目的是了解哪些因素对药物释放有影响，以便对药物释放进行建模，并建立一个预测药物释放动力学的数学模型。在两种模型药物，即几乎不溶的伊拉地平（ISR）和易溶的氯苯那敏（CPA）上测试了药物性质的影响。结果表明，无论药物性质如何，其对药物释放的影响不显著，释放动力学主要受四个因素控制：（i）膜中聚乙二醇的比例，（ii）片剂表面积，（iii）渗透剂比例，（iv）药物层聚合物等级。研究了每个关键制剂因素对释放机制的影响，并确定了它们的适用范围。开发了一种数学方法来预测改变PPOP控制因素时的药物释放动力学，并有助于更有效地设计PPOP。
