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. 2022 Apr 9;14(8):1528.
doi: 10.3390/polym14081528.

Formulation and Evaluation of Transdermal Gel Containing Tacrolimus-Loaded Spanlastics: In Vitro, Ex Vivo and In Vivo Studies

Randa Mohammed Zaki  1   2 , Mohamed A Ibrahim  3   4 , Doaa H Alshora  3 , Amal El Sayeh Abou El Ela  3   5
Affiliations

Formulation and Evaluation of Transdermal Gel Containing Tacrolimus-Loaded Spanlastics: In Vitro, Ex Vivo and In Vivo Studies

Randa Mohammed Zaki et al. Polymers (Basel). .

Abstract

Our goal was to prepare Span 60-based elastic nanovesicles (spanlastics (SPLs)) of tacrolimus (TCR) using the adapted ethanol injection method, characterize them, and evaluate their ability to improve the transdermal permeation of the active substance. The impact of two different concentrations of penetration enhancers, namely, propylene glycol and oleic acid, on the entrapment efficiency, vesicle size, and zeta potential was assessed. Moreover, in vitro release through a semipermeable membrane and ex vivo penetration through hairless rat skin were performed. Morphological examination and pharmacokinetics were performed for one selected formulation (F3OA1). TCR-loaded SPLs were effectively formulated with two different concentrations of permeation enhancers, and the effect of these enhancers on their physicochemical properties differed in accordance with the concentration and kind of enhancer used. The results of in vitro release displayed a considerable (p < 0.05) enhancement compared to the suspension of the pure drug, and there was a correlation between the in vitro and ex vivo results. The selected TCR-loaded nanovesicles incorporated into a gel base showed appreciable advantages over the oral drug suspension and the TCR-loaded gel. Additionally, the pharmacokinetic parameters were significantly (p < 0.05) improved based on our findings. Moreover, the AUC0−7 ng·h/mL form F3 OA1 was 3.36-fold higher than that after the administration of the TCR oral suspension.

Keywords: drug permeation; penetration enhancers; spanlastics; tacrolimus; transdermal gel.

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Conflict of interest statement

The authors hereby report that there are no conflicts of interest. The authors alone are accountable for the content and writing of this article.

Figures

Figure 1
Figure 1
TEM image of selected TCR-loaded SPL formulation (F3 OA 1).
Figure 2
Figure 2
(A) Pure TCR drug used and (B) DSC thermograms of selected lyophilized TCR-loaded SPLs (F3 OA 1).
Figure 3
Figure 3
In vitro release data of different permeation enhancers containing TCR-loaded SPLs. Results (n = 3) are presented as mean ± SD.
Figure 4
Figure 4
Ex vivo permeation data of different permeation enhancers containing TCR-loaded SPLs. Results (n = 3) are presented as mean ± SD.
Figure 5
Figure 5
In vitro release of TCR from F3 OA 1 SPL gel, and F3 OA 1 SPLs (n = 3, mean ± SD).
Figure 6
Figure 6
Ex vivo permeation of TCR from F3 OA 1 SPLs gel and F3 OA 1 SPLs (n = 3, mean ± SD) in rat skin.
Figure 7
Figure 7
Plasma concentration–time profile of TCR from F3 OA 1 SPLs gel compared to TCR-loaded gel and oral drug suspension in rats. Results (n = 5) are presented as mean ± SD.
See this image and copyright information in PMC

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