Optimization of transdermal permeation of non-steroidal anti-inflammatory agents and sunscreens

Ion pair formation has been utilized by many researchers to improve the permeation of various drugs through the skin, other biological and synthetic membranes. This technique is further being explored to increase the permeation of two well known non-steroidal anti-inflammatory drugs (NSAID's)---ibuprofen and benzydamine. Nuclear magnetic resonance (NMR) spectroscopy was used to demonstrate the existence of ion pairs and to rationalize the permeation behavior in terms of molecular interactions. The permeation of ibuprofen sodium was studied at various pH values and it was found that the flux across PDMS membrane increased significantly with increase in pH from 4.0 to 7.0. The permeability coefficient increased with the increase in the amount of unionized acid. To study the effect of ion pairing on the permeability of ibuprofen, ibuprofen was paired with different counter amines and highest flux was measured from ibuprofen triethylamine.; Similarly, the flux for benzydamine hydrochloride increased significantly with the amount of unionized base. Permeation of benzydamine hydrochloride across excised human skin showed similar profile as through PDMS. The octanol/water partition coefficient was directly related to steady state flux. To study the effect of ion pairing on penetration, benzydamine was paired with ibuprofen, benzoate or octane sulphonate ions. The NMR chemical shift changes were more significant when benzydamine was paired with ibuprofen or benzoate, which suggested that benzydamine was able to interact more strongly with ibuprofen and benzoate rather than with octane sulphonate. This was also reflected in the permeation characteristics, where ibuprofen and benzoate ions significantly increased the permeation of benzydamine.; A volunteer study was done in order to assess the penetration of sunscreens into and across the skin after topical application for commercial sunscreen formulation. Further, the effect of anatomical site on percutaneous absorption of sunscreen was measured. The volunteer study confirmed the systemic absorption of oxybenzone. A comparison of the skin penetration of sunscreen at different anatomical sites (face and back) demonstrates that as much as twice amount is present or retained in facial stratum corneum. This suggests that less amount of sunscreen would be required to produce the same protection as would be required on the back.; Further, studies were done to reduce the percutaneous absorption of oxybenzone. Effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) on the release and permeation of the sunscreen agent oxybenzone was investigated. The interaction between oxybenzone and HPbetaCD was studied by phase solubility analysis, thermal analysis and nuclear magnetic resonance spectroscopy. UV transmittance studies indicated that the presence of HPbetaCD did not suppress the UV absorbing properties of oxybenzone. The release and membrane permeation of oxybenzone was significantly reduced in the presence of equimolar, 2 times molar and 1, 2 and 4% of HPbetaCD. It is concluded that HPbetaCD can reduce the release/membrane diffusion of oxybenzone whilst retaining its efficacy as a sunscreen agent. This formulation strategy may be useful in controlling skin penetration of topically applied sunscreens and other chemicals. (Abstract shortened by UMI.)...