Optimizing and Evaluating the Transdermal Permeation of Hydrocortisone Transfersomes Formulation Based on Digital Analysis of the In Vitro Drug Release and Ex Vivo Studies

Abstract

Background: Transfersomes can be used to enhance transdermal drug delivery due to their flexibility and ability to incorporate various molecules. For example, hydrocortisone (HC), a corticosteroid, is taken by different routes and serves as immunosuppressive, anticancer, and antiallergenic; however, it is poorly absorbed by the skin.

Objective: Therefore, the current study suggested HC-loaded transfersomes as an alternative route of administration for reaching deeper skin layers or systemic circulation, to reduce the side effects of HC and improve its bioavailability.

Methods: HC transfersomes were prepared by the thin-film hydration method and characterized for their vesicular size, zeta potential, drug entrapment efficiency, elasticity, FTIR spectroscopy, in vitro drug release, ex vivo permeation, and irritancy in rabbits. The optimized formulation, F15 (containing HC 20 mg, egg phosphatidylcholine (EPC) 400 mg, and 75 mg of Span 80), was chosen because it showed the highest (p< 0.05) EE% (60.4±0.80) and optimized sustained in vitro drug release (Q8 = 87.9±0.6%).

Results: Extensive analysis of the drug release data from all formulas was performed using the DDSolver software which quantitatively confirmed the successful formulation. The Weibull equation was the best model to fit the release data compared to others, and the release mechanism was Fickian diffusion.

Conclusion: The simulated pharmacokinetic parameters showed that F15 had the highest AUC, MDT, and DE. Furthermore, F15 significantly enhanced HC permeation by 12-folds compared to the control through the excised rat's skin. The skin irritancy test has proven F15 safety and skin compatibility.

Keywords: DDSolver; Transfersomes; edge activator; hydrocortisone; in vitro release; permeation; transdermal.

Fig. (1)

Preparation technique of HC transfersomes by thin-film hydration method.

Fig. (2)

Optical microscopic images of some of the prepared HC transfersomes at 40x magnification.

Fig. (3)

The hydrophilic-hydrophobic balance of edge activators used in HC transfersomes formulations.

Fig. (4)

In vitro release of HC from the prepared transfersomes containing: a) SC; b) Span 20; c) Span 80; d) Brij 52; and e) Brij 58.

Fig. (5)

The correlation of residuals (Qo-Qc) versus time for HC transfersomal formulations (F1-F15) by different dissolution modelings.

Fig. (6)

The correlation of HC released amount (Qo) versus the predicted amount of HC released (Qc) of F1-F15 by the Weibull model, generated by DDSolver.

Fig. (7)

FT-IR spectra of a) HC; b) EPC; and c) F15, respectively.

Fig. (8)

SEM photographs a) Blank formula and; b) F15 transfersomes. The mean vesicle size of HC-loaded transfersomes significantly increased (p< 0.05) than the blank transfersomes, indicating the drug’s loading into the vesicles.

Fig. (9)

Cumulative HC permeated amount from F15 the reference product and the control through excised rat’s skin. Results are mean± SD (n =3).

Fig. (10)

Linear correlation of the percentage of drugs permeated in the ex vivo study compared to the percentage of drug release in vitro for the selected formula F15. The short Error Bars indicate the values are concentrated and reliable.

Fig. (11)

Pictures of the skin irritation study carried out in rabbits for the control (histamine injection) and F15 transfersomal formula; 1h and 6h after sample application.