Bioanalytical Considerations for your Dermal Pharmaceutical Programs
Does your drug require sustained release or suffer from first pass metabolism losses?
Have you considered transdermal delivery via cream gel or patch?
How does bioanalysis differ for oral or dermal delivery?
The dermis is the largest organ of the human body and provides a barrier and protection against the external environment. Sometimes it is necessary or desirable to treat diseases of the dermis or deliver drug through the dermis. Dermal delivery can provide controlled and sustained drug release over time as well as avoid first-pass metabolism and improve patient compliance. In these cases, topical dermal application through creams, gels and patches are the most common formulations. A comprehensive PK package to support these programs can be challenging and requires the analysis of multiple matrices.
Dermal PK and TK present different obstacles than oral delivery, among which are measurement of:
· Skin penetration rates
· Systemic exposure
· Local exposure
Typically, dermal delivery seeks one of two outcomes: high local concentration with minimal systemic exposure or maximal skin penetration and systemic exposure with minimal residual concentrations. In the case of skin penetration studies using a Franz diffusion cell, analysis may also need to accurately quantitate large concentration gradients. In these cases, it is necessary to develop wide range or dual range assays capable of measuring the extremes of the expected concentrations.
Plasma or serum typically serve as the primary matrix to determine systemic exposure, but secondary matrices such as tissue and dosing medium are also required for supporting data. In order to obtain representative data, homogenization of intact skin tissue or dissected epidermis, dermis and subcutaneous tissues is required. Stratum corneum tape stripping may be necessary and provides an additional matrix for extraction and evaluation. Having a bioanalytical lab skilled in working with a vast array of matrices can provide a real savings in method development time and cost.