The greatest obstacle for transdermal drug delivery is the stratum corneum that forms a primary rate limiting barrier to the permeation of drugs across the skin. It consists of dead, flattened cells filled with keratin that are embedded in a lipid matrix. The stratum corneum has been described as hydrophilic protein bricks embedded in a hydrophobic lipid mortar. There has been a considerable interest in the potential usefulness of the topical application of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indomethacin and diclofenac. These weak acidic drugs are effective in the treatment of rheumatoid arthritis and osteoarthritis.
However, the disadvantage of the topical route for drug delivery is that a relatively high dose is required to deliver therapeutic amounts of drug across the skin. To improve the topical delivery of drugs, several strategies are available including the use of penetration enhancers and optimization of drug release from the formulation. The pH of the formulation has an impact on the penetration rate of weak acidic and weak basic drugs.
The flux of ibuprofen from a saturated solution at pH values ranging from 2.2 to 9.0 using human skin in vitro has been studied. It was reported that flux of the drug increased with an increase in the pH of the solution. The reason behind this effect was unclear. However, ibuprofen was reported to show a considerable surface activity. Since surfactants are well known penetration enhancers, it is possible that ibuprofen has acted as surfactant and thus impaired the skin permeability barrier. Hence, it is planned to study effect of ibuprofen concentration, in saturated solutions, on its permeation across skin. It is a known concept that an increase in concentration of drug in the vehicle results in enhanced flux due to increased thermodynamic activity. One delivery mechanism was designed by keeping thermodynamic activity constant while increasing the drug concentration in the delivery mechanism. This was done by preparing saturated solutions of ibuprofen, of different concentrations, using disodium hydrogen phosphate solutions of various molar strengths. The permeation of ibuprofen from its saturated solutions across rat epidermis and human epidermis was studied, and the results were compared with those obtained from silastic membrane.
The transdermal route now ranks with oral treatment as the most successful innovative research area in drug delivery, with around 40% of the drug delivery candidate products under clinical evaluation related to transdermal or dermal system. The worldwide transdermal patch market approaches £ 2 billion, based on only ten drugs including scopolamine, nitroglycerine, clonidine, estrogen, testosterone, fentanyl, and nicotine, with a lidocaine patch soon to be marketed.
USPTO Backgrounds
USPTO Backgrounds