In-vitro assessment of indomethacin release from dermatological formulations using cellulose membrane, excised pig and human cadaver skin barriers

Indomethacin/Indometacin is a non-steroidal anti-inflammatory drug (NSAID) that exhibits antipyretic and analgesic properties. Indomethacin has been shown to be an effective anti-inflammatory agent, appropriate for long-term use in rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. Indomethacin is available as a capsule dosage form in three different strengths, 25; 50 and SR 75 mg. It is also available as suspension in the strength of 25 mg/ml and 50 mg suppository.;The main disadvantage of oral non-selective COX inhibitors NSAIDs are they can be toxic to kidney and increases the risk of gastrointestinal bleeding. A population using NSAID's are at increased risk for serious gastrointestinal (GI) complications. NSAIDs such as Indomethacin, Meloxicam, Ibuprofen etc may cause ulcers, bleeding, or holes in the stomach or intestine. The risk of having a heart attack or a stroke is also increased in people who take non-steroidal anti-inflammatory drugs (NSAIDs).;An attempt was made to evaluate the feasibility of developing topical formulations of this drug, as a means to overcome its gastrointestinal complications and cardiovascular risks when administered as an oral dosage form.;Various dermatological formulations of Indomethacin were formulated using bases like HPMC gel and anionic and non-ionic emulsion based cream with an optimum pH and further evaluated for in vitro drug release characteristics using cellulose membrane, pig skin and human cadaver skin. The hierarchy of drug release was observed to be as follows: HPMC gel system > non-ionic emulsion based cream > anionic emulsion based cream. Further, the effects of various penetration enhancers like Propylene Glycol (PG) , Dimethyl Sulfoxide (DMSO) and Diethylene glycol modoethyl ether (DGME) at a concentration of 5%, 10% and 15% on drug release were evaluated. In most cases, the addition of enhancers had a little or no effect in enhancing the drug release from these bases.;Furthermore, Pig skin and Human cadaver skin were used as a barrier to assess the in-vivo drug release from the formulation. The release of drug was significantly reduced compared to cellulose membrane data with the similar release pattern. The release data were treated to determine the physical parameters that influence drug diffusion, and the values for the steady flux and diffusion coefficient were found to be the highest with HPMC gel based formulation containing 1% Indomethacin with 5 % DMSO as the penetration enhancer yielding the lowest values for the lag time and partition coefficient.