Showing papers by "Ayman El-Kattan published in 2000"

Enhancement of transdermal drug delivery: chemical and physical approaches.

Abstract: Transdermal drug delivery has been intensively studied over the last two decades because of the many advantages offered by this route of administration. However, the number of drugs used in transdermal drug delivery systems has been somewhat limited, in part resulting from the formidable barrier to drug permeation presented by the upper layer of the skin, the stratum corneum. In order to overcome this, different strategies have been implemented to render the skin more permeable to drugs. These strategies include both chemical and physical approaches. In this review, we outline the enhancing activities and mechanisms of action of some of the more extensively studied chemical penetration enhancers (oxazolidinones, propylene glycol, and epidermal enzymes). In addition, we discuss novel physical strategies, such as the use of microneedles or electroporation.

Evaluation of a human bio-engineered skin equivalent for drug permeation studies

Abstract: Purpose. To test the barrier function of a bio-engineered human skin (BHS) using three model drugs (caffeine, hydrocortisone, and tamoxifen) in vitro. To investigate the lipid composition and microscopic structure of the BHS. Methods. The human skin substitute was composed of both epidermal and dermal layers, the latter having a bovine collagen matrix. The permeability of the BHS to three model drugs was compared to that obtained in other percutaneous testing models (human cadaver skin, hairless mouse skin, and EpiDerm™). Lipid analysis of the BHS was performed by high performance thin layered chromatrography. Histological evalulation of the BHS was performed using routine H&E staining. Results. The BHS mimicked human skin in terms of lipid composition, gross ultrastructure, and the formation of a stratum corneum. However, the permeability of the BHS to caffeine, hydrocortisone, and tamoxifen was 3-4 fold higher than that of human cadaver skin. Conclusions. In summary, the results indicate that the BHS may be an acceptable in vitro model for drug permeability testing.

Effect of formulation variables on the percutaneous permeation of ketoprofen from gel formulations.

Abstract: The objectives of our study were to evaluate the effect of four terpene enhancers, enhancer lipophilicity, and ethanol concentration using hydroxypropyl cellulose (HPC) and two Pluronic F-127 (PF-127) gel formulations on the percutaneous permeation of ketoprofen. All experiments were conducted using hairless mouse skin in vitro. Data recorded over 24 hr was compared with that for control gels (containing no terpene) using Franz diffusion cells. In the three gel formulations, the highest increase in the ketoprofen permeation was observed using limonene followed by nerolidol, fenchone, and thymol. Relationships were established between terpene lipophilicity, enhancement ratios for ketoprofen flux (ERflux), and the cumulative amount of ketoprofen after 24 hr (Q24) from the three gel formulations. However, no correlation was established between terpene lipophilicity and ketoprofen skin content values at 24 hr. Ethanol had a synergistic effect on the enhancing activity of the terpenes. Increasing the concentration of ethanol from 10% to 50% was associated with an increase in the permeation of ketoprofen. For example, use of PF-127 gel control (no terpene was included) containing 10% ethanol resulted in a ketoprofen flux of 19 +/- 2 microg/cm2 h and 481 +/- 131 microg/cm2 for Q24. Furthermore, for PF-127 containing 33% ethanol the flux was 34 +/- 3 microg/cm2 h and Q24 was 1,420 +/- 111 microg/cm2. However, HPC gel control that contained 50% ethanol resulted in a ketoprofen flux of 67 +/- 6 microg/cm2 h and 2,839 +/- 222 microg/cm2 for Q24.