Application of synthetic membranes in establishing bio-predictive IVPT for testosterone transdermal gel

Loqman A Mohamed; Nahid Kamal; Khaled H Elfakhri; Sarah Ibrahim; Muhammad Ashraf; Ahmed S Zidan

doi:10.1016/j.ijpharm.2020.119572

Application of synthetic membranes in establishing bio-predictive IVPT for testosterone transdermal gel

Int J Pharm. 2020 Aug 30:586:119572. doi: 10.1016/j.ijpharm.2020.119572. Epub 2020 Jun 26.

Authors

Loqman A Mohamed¹, Nahid Kamal², Khaled H Elfakhri², Sarah Ibrahim³, Muhammad Ashraf², Ahmed S Zidan⁴

Affiliations

¹ Division of Pharmaceutical Manufacturing II, Office of Pharmaceutical Manufacturing Assessment, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, MD 20993, USA.
² Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, MD 20993, USA.
³ Division of Bioequivalence, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, MD 20993, USA.
⁴ Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, MD 20993, USA. Electronic address: Ahmed.Zidan@fda.hhs.gov.

PMID: 32599131
DOI: 10.1016/j.ijpharm.2020.119572

Abstract

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 AUC_0-24 and C_max. 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 × X^3.6. 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 AUC_0-24 and C_max. 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.

Keywords: IVIVR; Percutaneous absorption; Permeation; Synthetic membranes; Testosterone gel.

Published by Elsevier B.V.

Publication types

Validation Study

MeSH terms

Administration, Cutaneous
Area Under Curve
Diffusion
Drug Liberation
Gels
Humans
In Vitro Techniques
Male
Membranes, Artificial*
Permeability
Randomized Controlled Trials as Topic
Skin / metabolism*
Skin Absorption*
Testosterone / administration & dosage*
Testosterone / pharmacokinetics

Substances

Gels
Membranes, Artificial
Testosterone