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. 2022 Aug 12;13(8):1304.
doi: 10.3390/mi13081304.

Simvastatin Loaded Dissolvable Microneedle Patches with Improved Pharmacokinetic Performance

Zulcaif  1 , Nadiah Zafar  1 , Asif Mahmood  2 , Rai Muhammad Sarfraz  3 , Abdelhamid Elaissari  4
Affiliations

Simvastatin Loaded Dissolvable Microneedle Patches with Improved Pharmacokinetic Performance

Zulcaif et al. Micromachines (Basel). .

Abstract

Microneedle patches (MNPs) are one of the emerging approaches for drug delivery involving minimal invasion and improved skin penetration of macro- and micro-entities. Herein, we report dissolvable microneedle patches (dMNPs) as a novel tool for better systemic delivery of Simvastatin in the management of hypocholesteremia. Thiolated chitosan (TC), polyvinyl pyrolidone (PVP) and polyvinyl alcohol (PVA) were employed in the development of dMNPs. Developed patches were characterized through SEM, FTIR, DSC, TGA, PXRD, dissolution testing, tensile strength, elongation (%), skin irritation studies, moisture content and pharmacokinetic evaluation. dMNP F26 exhibited excellent tensile strength (9.85 MPa), penetration potential (~700 µm), moisture content (5.95%), elongation (35.54%) and Simvastatin release of 77.92%. Pharmacokinetic properties were also improved, i.e., Cmax 1.97 µg/mL, tmax 9 h, MRT 19.9 h and AUC 46.24 µg·h/mL as compared to Simvastatin solution displaying Cmax 2.55 µg/mL, tmax 3 h, MRT 5.91 h and AUC 14.20 µg·h/mL thus confirming higher and improved bioavailability. Kinetic modelling revealed zero order as the best fit model based on regression coefficient. Histopathological findings proved the biocompatibility of the developed dMNPs.

Keywords: PVA; PVP-K30; dissolving microneedle; pharmacokinetic profile; simvastatin; sustained release; thiolated chitosan; transdermal drug delivery.

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Conflict of interest statement

Authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Microneedle patch F26, (a) macroscopic aerial view, (b) macroscopic side view and (c) microscopic view showing clear pointed needles.
Figure 2
Figure 2
(a) Results of thickness, tensile strength and elongation (%), (b) schematic diagram to represent measurement of tensile strength and elongation of dMNP.
Figure 3
Figure 3
SEM photomicrographs of F26 at different magnification powers (a) ×40, (b) ×40 (aerial view), (c) ×100 (side view) and (d) ×500.
Figure 4
Figure 4
Post insertion microscopic view of the layers, (a) microneedle patch applied on paraffin M film 09 layers, (b) MNP removed from layers, (c) 1st layer of paraffin M film, (d) 2nd layer of paraffin M film, (e) 3rd layer of paraffin M film, (f) 4th layer of paraffin M film, (g) 5th layer of paraffin M film, (h) 6th layer of paraffin M film, (i) sharp microneedles applied on layers, (j) after MNP insertion microscopic view, (k) microscopic view of 1st layer, (l) microscopic view of 2nd layer, (m) microscopic view of 3rd layer, (n) microscopic view of 4th layer, (o) microscopic view of 5th layer, (p) microscopic view of 6th layer with absence of microneedle mark.
Figure 5
Figure 5
FTIR Spectra of (a) PVP-K30, (b) PVA (c) Thiolated Chitosan, (d) Simvastatin and (e) Simvastatin loaded dMNP.
Figure 6
Figure 6
DSC thermograms of (a) PVA, (b) thiolated chitosan, (c) PVP-k30, (d) Simvastatin and (e) Simvastatin loaded dMNPs.
Figure 7
Figure 7
TGA thermograms of (a) PVA, (b) Thiolated Chitosan, (c) PVP, (d) Simvastatin and (e) Dissolvable microneedle patch.
Figure 8
Figure 8
PXRD diffractograms of (a) Simvastatin, (b) PVA, (c) Thiolated chitosan, (d) PVP and (e) Simvastatin-loaded dMNPs.
Figure 9
Figure 9
Irritation testing after application of dMNP, (a) Microneedle patch loaded with Simvastatin on skin before application at 0 h, (b) After 48 h of application.
Figure 10
Figure 10
Histopathological examination of rabbit skin (a) before application of dMNP (b) after application of dMNP for 30 s and (c) after application of dMNP for 1 min.
Figure 11
Figure 11
In vitro release of Simvastatin loaded dMNP and Simvastatin solution at pH 7.4.
Figure 12
Figure 12
HPLC chromatographs of Simvastatin, (a) in mobile phase, (b) in spiked plasma and (c) after application of dMNP.
Figure 13
Figure 13
Plasma concentration vs. time graph.
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