International Journal of Nanomedicine (Aug 2022)

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

  • Sikandar M,
  • Shoaib MH,
  • Yousuf RI,
  • Ahmed FR,
  • Ali FR,
  • Saleem MT,
  • Ahmed K,
  • Sarfaraz S,
  • Jabeen S,
  • Siddiqui F,
  • Husain T,
  • Qazi F,
  • Imtiaz MS

Journal volume & issue
Vol. Volume 17
pp. 3463 – 3481

Abstract

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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 Imtiaz1 1Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan; 2Jinnah College of Pharmacy, Sohail University, Karachi, 74000, Pakistan; 3Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, PakistanCorrespondence: Muhammad Harris Shoaib, Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan, Email [email protected]; [email protected]: 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: halloysite nanotube, transdermal, nanocomposite, controlled release, GastroPlus

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