Authors: Krishnaiah, Yellela S.; Al-Saidan, Saleh M.

Source: Current Drug Delivery, Volume 5, Number 1, January 2008 , pp. 70-76(7)

Publisher: Bentham Science Publishers

Abstract:

The objective of the study was to design membrane-controlled transdermal therapeutic system (TTS) for trimetazidine. The optimization of (i) concentration of ethanol-water solvent system, (ii) HPMC concentration of drug reservoir and (iii) limonene concentration in 2% w/v HPMC gel was done based on the in vitro permeation of trimetazidine across excised rat epidermis. A limonene-based membrane-controlled TTS of trimetazidine was fabricated and evaluated for its in vivo drug release in rabbit model. The in vitro permeation of trimetazidine from water, ethanol and selected concentrations (25, 50 and 75% v/v) of ethanol-water co-solvent systems showed that 50% v/v of ethanol-water solvent system provided an optimal transdermal flux of 233.1±3.8 μg/cm2.h. The flux of the drug decreased to 194.1±7.4 μg/cm2.h on adding 2% w/v of HPMC to ethanolic (50% v/v ethanol-water) solution of trimetazidine. However, on adding selected concentrations of limonene (0, 2, 4, 6 and 8% w/v) to 2% w/v HPMC gel drug reservoir, the flux of the drug increased to 365.5±7.1 μg/cm2.h. Based on these results, 2% w/v HPMC gel drug reservoir containing 6% w/v of limonene was chosen as an optimal formulation for studying the influence of rate-controlling EVA2825 membrane and adhesive-coated EVA2825 membrane. The flux of the drug across EVA2825 membrane (mean thickness 31.2 μm) decreased to 285.8±2.2 μg/cm2.h indicating that the chosen membrane was effective as rate-controlling membrane. On applying an adhesive coat (mean thickness 10.2 μm) to EVA2825 membrane, the drug flux further decreased to 212.4±2.6 μg/cm2.h. However, the flux of the drug across adhesive-coated EVA2825 membrane-rat epidermis composite was 185.9±2.9 μg/cm2.h, which is about 2-times higher than the desired flux. The fabricated limonene-based TTS patch of trimetazidine showed a mean steady state plasma concentration of 71.5 ng/mL for about 14 h with minimal fluctuation when tested in rabbits. It was concluded from the investigation that the limonene-based TTS patch of trimetazidine provided constant drug delivery across the skin in rabbit model.

Keywords: Transdermal; TTS; trimetazidine; limonene; in vitro permeation; rat epidermis; in vivo release; rabbit

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156720108783330970

Publication date: 2008-01-01

More about this publication?

• The aim of Current Drug Delivery is to publish peer-reviewed articles, short communications, short and in-depth reviews in the rapidly developing field of drug delivery. Modern drug research aims to build in delivery properties of a drug at the design phase, however in many cases this ideal cannot be met and the development of delivery systems becomes as important as the development as the drugs themselves.
  
  The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.
  
  The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.

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