Development of domperidone bilayered matrix type transdermal patches: physicochemical, in vitro and ex vivo characterization

作者：Madishetti S K; Palem C R; Gannu R; Thatipamula R P; Panakanti P K; Yamsani M R^*

来源：Daru-Journal of Faculty of Pharmacy, 2010, 18(3): 221-229.

• Domperidone
• Bilayered Transdermal patches
• In vitro release
• Ex vivo permeation

Background and the purpose of the study: Domperidone (DOM) is a dopamine- receptor (D(2)) antagonist, which is widely used in the treatment of motion-sickness. The pharmacokinetic parameters make DOM a suitable candidate for transdermal delivery. The purpose of the present investigation was to develop transdermal delivery systems for DOM and to evaluate their physicochemical characteristics, in vitro release an ex vivo permeation through rat abdominal skin and their mechanical properties.
Methods: Bilayered matrix type transdermal drug delivery systems (TDDS) of DOM were prepared by film casting technique using hydroxypropyl methyl cellulose as primary and Eudragit RL 100 as secondary layers. Brij-35 was incorporated as a solubilizer, d-limonene and propylene glycol were employed as permeation enhancer and plasticizer respectively. The prepared TDDS were extensively evaluated for in vitro release, moisture absorption, moisture content, water vapor transmission, ex vivo permeation through rat abdominal skin, mechanical properties and stability studies. The physicochemical interaction between DOM and polymers were investigated by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR).
Results: All the formulations exhibited satisfactory physicochemical and mechanical characteristics. The optimized formulation F6 showed maximum cumulative percentage of drug release (90.7%), permeation (6806.64 mu g) in 24 hrs, flux (86.02 mu g /hr/cm(2)) and permeation coefficient of 0.86x10(-2) cm/hr. Values of tensile strength (4.34 kg/mm(2)) and elastic modulus (5.89 kg/cm(2)) revealed that formulation F6 was strong but not brittle. DSC and FTIR studies showed no evidence of interaction between the drug and polymers. A shelf life of 2 years is predicted for the TDDS.
Conclusions: Domperidone bilayered matrix type transdermal therapeutic systems could be prepared with the required flux and suitable mechanical properties.

• 出版日期2010