Controlled release of gemfibrozil from novel potential devices

In recent years, pharmaceutical research was focused on the development of formulations suitable for application in controlled drug delivery, owing to their advantages over the conventional pharmaceutical forms [1]. They include the maintenance of the plasma concentration of a drug in the therapeutic range and the reduction of the administration frequency thus allowing to reduce the incidence of the side effects [2]. New materials were exploited with the aim to develop transdermal patches. These systems are based on the use of synthetic membranes to control the passage of the drug through the skin and to bypass the gastrointestinal tract. In this way, it is possible to increase the drug bioavailability and to reduce the irritation effect [3]. Recently, Algieri et. al. [4] and Donato et al. [5] investigated the possibility to employ mixed matrix membranes (MMMs) zeolite-loaded for the controlled release of Ibuprofen and tramadol, respectively. Authors demonstrated as the presence of hydrophilic zeolite crystals allowed to modulate the release kinetics of both drugs with respect to the pure polymer membrane. The present work was focused on the development of MMMs for the transdermal delivery of Gemfibrozil (2,2-Dimethyl-5-(2,5-dimethylphenoxy) pentanoic acid). This drug is a lipid-lowering agent used in dyslipidemias characterized by an increase of triglycerides and a decrease of high density lipoprotein (HDL). Its short biological half life (~1.5 h) requires multiple daily dosage, therefore, a controlled release system may be convenient to reduce the frequency of administration, to avoid toxicity an to improve patient compliance [6]. In particular, a transdermal delivery of the gemfibrozil permits to reduce the side effects which generally occur at gastrointestinal tract. The polymer used for the preparation of the membranes was the polydimethylsiloxane (PDMS) which is a rubbery biocompatible material. The elastomeric property of PDMS permits the preparation of defect-free membranes due to the high mobility of the polymeric chains [7]. The effect of zeolite and drug content on the release kinetics was investigated. Initially, morphological characterizations as well as swelling ratio, erosion and moisture uptake were performed. Subsequently, in vitro and ex-vivo release studies were carried out to identify the best promising system as delivery device. The experimental results were fitted with different mathematical models (zero order, first order, Higuchi, Bhaskar, and Korsemeyer-Peppas) to interpret the drug release mechanism from the different MMMs. Interestingly, ex-vivo experiment results showed a constant release of gemfibrozil in the time. These data reflect one of the main features of a controlled release system namely the development of zero order release devices. Our study evidences the potential application of the prepared membranes as transdermal devices for the controlled release of the gemfibrozil.