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. 2022 Aug 4:17:3463-3481.
doi: 10.2147/IJN.S367540. eCollection 2022.

Nanoclay-Based Composite Films for Transdermal Drug Delivery: Development, Characterization, and in silico Modeling and Simulation

Muhammad Sikandar  1 , Muhammad Harris Shoaib  1 , Rabia Ismail Yousuf  1 , Farrukh Rafiq Ahmed  1 , Fatima Ramzan Ali  1   2 , Muhammad Talha Saleem  1 , Kamran Ahmed  1 , Sana Sarfaraz  3 , Sabahat Jabeen  1 , Fahad Siddiqui  1 , Tazeen Husain  1 , Faaiza Qazi  1 , Muhammad Suleman Imtiaz  1
Affiliations

Nanoclay-Based Composite Films for Transdermal Drug Delivery: Development, Characterization, and in silico Modeling and Simulation

Muhammad Sikandar et al. Int J Nanomedicine. .

Abstract

Purpose: Halloysite nanotubes (HNTs) are a versatile and highly investigated clay mineral due to their natural availability, low cost, strong mechanical strength, biocompatibility, and binding properties. The present work explores its role for retarding and controlling the drug release from the composite polymer matrix material.

Methods: For this purpose, nanocomposite films comprising propranolol HCl and different concentrations of HNTs were formulated using the "solution casting method". The menthol in a concentration of 1% w/v was used as a permeation enhancer, and its effect on release and permeation was also determined. Quality characteristics of the nanocomposite were determined, and in vitro release and permeation studies were performed using the Franz diffusion system. The data was analyzed using various mathematical models and permeation parameters. Optimized formulation was also subjected to skin irritation test, FTIR, DSC, and SEM study. Systemic absorption and disposition of propranolol HCl from the nanocomposites were predicted using the GastroPlus TCAT® model.

Results: The control in drug release rate was associated with the higher concentration of HNTs. F8 released 50% of propranolol within 8 hours (drug, HNTs ratio, 1:2). The optimized formulation (F6) with drug: HNTs (2:1), exhibited drug release 80% in 4 hours, with maximum flux of 145.812 µg/cm2hr. The optimized formulation was found to be a non-irritant for skin with a shelf life of 35.46 months (28-30 ℃). The in silico model predicted Cmax, Tmax, AUCt , and AUCinf as 32.113 ng/mL, 16.58 h, 942.34 ng/mL×h, and 1102.9 ng/mL×h, respectively.

Conclusion: The study demonstrated that HNTs could be effectively used as rate controlling agent in matrix type transdermal formulations.

Keywords: GastroPlus; controlled release; halloysite nanotube; nanocomposite; transdermal.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Diagrammatic illustrations of propranolol-loaded HNTs-PVA nanocomposite transdermal films.
Figure 2
Figure 2
The in vitro release profile of propranolol HCl transdermal nanocomposite film formulations (F1–F8).
Figure 3
Figure 3
The in vitro permeation profile of propranolol HCl transdermal nanocomposite film formulations (F1–F8).
Figure 4
Figure 4
HPLC-UV chromatogram of propranolol HCl (A and B) and transdermal nanocomposite formulation F6 (C and D).
Figure 5
Figure 5
FTIR spectrum of the propranolol HCl, HNT’s, PVA, methanol and transdermal nanocomposite formulation F6.
Figure 6
Figure 6
Thermograms, representing thermal transitions, of (A) propranolol HCl (B) HNT (C) PVA (D) PVA/HNT nanocomposite film and (E) optimized formulation F6.
Figure 7
Figure 7
SEM image of PVA film (A) without HNTs and (B) with HNTs.
Figure 8
Figure 8
Irritation study on mice. (A) animals in the animal cage (B) animal skin shaved (C) film applied on the shaved skin (D) the skin after removal of the patch (E) control animal after treatment with formalin, irritation or redness on the skin can be seen.
Figure 9
Figure 9
Plasma concentration–time profiles of (A) propranolol HCl oral 80 mg tablet formulation and simulated 20 mg transdermal nanocomposite propranolol film formulation F6 (B) propranolol HCl oral 80 mg tablet formulation and simulation of multiple doses (4 doses) of F6 using GastroplusTM PBPK modeling software.
See this image and copyright information in PMC

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