The current study investigated the use of synthetic membranes in developing a bio-predictive in vitro permeation testing (IVPT) method for 1.62% testosterone gel. The IVPT studies were carried out using both Franz (FC), and Flow-through (FTC) diffusion cells. The experimental variables included the type of synthetic membranes (hydrophilic polyamide nylon, polysulfone tuffryn and STRAT-M (SM) membrane) and the type of receiver media (phosphate buffer containing various concentrations of sodium lauryl sulfate). In vivo drug release rates were obtained from published reports for 1.62% testosterone gel applied to either abdominal area (treatment group A), upper arms/shoulders (treatment group B), or alternating between abdomen and arms/shoulders (treatment group C). The in vitro-in vivo correlations were established using GastroPlus software. The best IVPT method was selected based on establishing point-to-point correlation with the in vivo data of treatment group A with minimal prediction errors (%PE) of AUC0-24 and Cmax. The results showed that the IVPT method which employed the FTC diffusion system, SM membrane and phosphate buffer without surfactant established the best IVIVR model with a correlation coefficient (R2) of 0.9966 and an exponential function of Y = (1.35)5 × X3.6. The in vivo data obtained from treatment group A and B was used for internal validation of the prediction model. The validation data was acceptable, with %PE of less than 10% for both AUC0-24 and Cmax. In conclusion, these results suggest that bio-predictive IVPT methods for testosterone gels may be developed using synthetic membranes and diffusion apparatus by varying the composition of the receiver medium.
By Mohamed LA, Kamal N, Elfakhri KH, Ibrahim S, Ashraf M, Zidan AS