Transdermal Drug Delivery System of Aceclofenac for Rheumatoid Arthritis and the Effect of Permeation Enhancers: In vitro and in vivo Characterization

Abstract

A B S T R A C T Aceclofenac is a non steroidal anti inflammatory drug which is used to manage the chronic pain and inflammation in the patients of rheumatoid arthritis. But it is associated with short half-life (2-3 h) and gastro-intestinal side effects. To overcome these problems the transdermal delivery of aceclofenac can be investigated for prolonged relief from pain and local inflammation in arthritis. The transdermal films of aceclofenac were prepared using two different permeation enhancers (A nonionic surfactant-Span-20 and a terpene-d limonene) in two different concentrations with solvent evaporation method. The prepared transdermal films were subjected to physicochemical evaluations, ex vivo permeation and in vivo anti-inflammatory studies. The prepared matrix type transdermal films showed high drug content ranging from 94.90±1.40 to 98.20±2.60 with completely flat surface and the folding endurance in the range of 120.0±9.24 to 182.0±4.20. The scanning electron microscopy showed that the drug particles were dispersed in the matrix of the film and was found to be projected on the surface of film also. The ex vivo permeation study in the modified Franz diffusion apparatus through excised rat abdominal skin in pH 7.4 phosphate buffer showed prolonged drug permeation ranging from 61.02-93.4%. The films prepared with permeation enhancers showed greater percent drug permeated at the end of 24 h. The d-limonene showed the greater permeation enhancement effect as compared to that of Span 20. Increasing the concentration of enhancers showed the increased permeation of the drug. The transdermal films were found to be non-irritant to the skin in primary skin irritation test on Wistar rats. The transdermal films with permeation enhancers showed the greater anti inflammatory activity in carrageenan induced hind rat paw edema model. It was concluded that the transdermal films of aceclofenac have the great potential for the use in treatment of arthritis. And d-limonene can have greater effect on increasing the drug flux and eliciting the anti-inflammatory effect as compared to that of Span 20 for the transdermal delivery of aceclofenac.

Diclofenac transdermal patch versus the sustained release tablet: A randomized clinical trial in rheumatoid arthritic patients

“…The increase was directly proportional to the concentration of turpentine oil and was in good agreement with previous studies [18][19][20]. Several groups have also reported turpentine oil and terpene-based enhancers as promising penetration enhancers with a greater effect on increasing the flux and anti-inflammatory activity [21,22].…”

Evaluation of a root extract gel from <i>Urtica dioica</i> (Urticaceae) as analgesic and anti-inflammatory therapy in rheumatoid arthritis in mice

“…The conventionally used NSAIDs in RA have also been developed into topical or transdermal forms for various benefits, including reduced adverse effects, reduced drug dosage, improved patient compliance, and prolonged drug release [6,8,20]. Herbal drugs have long been used in traditional medicine for various conditions of pain and inflammation including arthritis.…”

“…However, oral NSAIDs are often needed at high dosing frequencies and show side effects, such as gastric irritation and moderate plasma level fluctuations, which may lead to the chance of an overdose. Thus, to overcome these limitations and to improve bioavailability, prolong the effects, and minimize side effects, topical or transdermal delivery has been investigated for various NSAIDs [6][7][8].…”

Preparation and assessment of ketamine hydrogels for prolonged transdermal anaesthesia

“…A standard irritant (0.8 % v/v aqueous solution of formaldehyde) was applied to Group IV (standard). After 24 h, the application sites were scored for erythema and oedema [18].…”