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Predicting the Percutaneous Penetration of Cosmetic Ingredients
By: Sara Farahmand, PhD, University of Cincinnati College of Pharmacy; and Howard I. Maibach, MD, PhD, University of California School of Medicine
Posted: March 30, 2010, from the April 2010 issue of Cosmetics & Toiletries.
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Gender: Although there are significant differences in the general appearance of skin and distribution of hair follicles between males and females, there is no convincing evidence to suggest major differences in barrier function. A pharmacokinetic study of nicotine demonstrated the higher values for apparent nicotine elimination rate constants in women. Greater subcutaneous lipid in women compared with men could be hypothesized to affect transdermal drug delivery but this has not been confirmed. In general, bioavailability and protein binding do not appear to be significantly affected by gender.14 Further studies are needed to address the gender effect on the efficiency of transdermal drug delivery.
Other: Formation of skin depots and the duration of effects varies in different subjects. This is known to cause interindividual variations in the plasma concentration profiles of clonidine after the delivery system’s removal. In some subjects the plasma concentration rises and in others, it declines.15 Local blood flow is considered as a limiting factor for the exchange rate of transdermally applied nicotine. This explains the increased drug release from the TTS during exercise.
Plasma Concentration and Molecule Properties
The models obtained here suggest the possibility of a determinant correlation between Cmax of transdermally administered drugs and their molecular properties. These models were developed based on the available data for all the pharmacokinetically studied marketed drugs except fentanyl and clonidine, which showed exceptionally high Cmax values. Since this trial evaluates the relationship of in vivo absorption data of transdermally applied drugs with their structural features, only a small data set was available. Although this may reduce the predictive power of the model for further molecules, correlations are evaluated for a relevant data set that corresponds to a group of drugs with proven clinical efficacy after transdermal absorption.
According to the standardized partial regression coefficients, the number of hydrogen bond acceptor groups (HA) has the largest contribution in predicting Cmax in both equations, in the context of the other predictor variables in the model. This finding is in accordance with the previous studies, where HA was determined to be a main parameter in predicting permeability coefficient.3
Eq. 4 and 5 disclose that the Cmax is positively correlated to the HA. Lipinski et al. proposed that a large number of hydrogen bond acceptor sites may potentially delay skin permeation. Poor absorption or permeation is more likely when there are more than five hydrogen bond donors or ten hydrogen bond acceptors present on the molecule.16