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Investigating Halloysite Nanotubes as a Potential Platform for Oral Modified Delivery of Different BCS Class Drugs: Characterization, Optimization, and Evaluation of Drug Release Kinetics

Authors Husain T, Shoaib MH, Ahmed FR, Yousuf RI, Farooqi S, Siddiqui F, Imtiaz MS, Maboos M, Jabeen S

Received 1 January 2021

Accepted for publication 17 February 2021

Published 1 March 2021 Volume 2021:16 Pages 1725—1741

DOI https://doi.org/10.2147/IJN.S299261

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J. Webster


Tazeen Husain, Muhammad Harris Shoaib, Farrukh Rafiq Ahmed, Rabia Ismail Yousuf, Sadaf Farooqi, Fahad Siddiqui, Muhammad Suleman Imtiaz, Madiha Maboos, Sabahat Jabeen

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan

Correspondence: Muhammad Harris Shoaib; Farrukh Rafiq Ahmed
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan
Email [email protected]; [email protected]

Purpose: This study systematically investigated the potential of four model drugs (verapamil HCl, flurbiprofen, atenolol, and furosemide), each belonging to a different class of Biopharmaceutics Classification Systems (BCS) to be developed into oral modified release dosage forms after loading with halloysite nanotubes (HNTs).
Methods: The drugs were studied for their loading (mass gain %) by varying solvent system, method, pH, and ratios of loading into the nanotubes using D-optimal split-plot design with the help of Design Expert software. Drug-loaded halloysites were characterized by XRD, DTA, FTIR, SEM, and HPLC-UV-based assay procedures. Dissolution studies were also performed in dissolution media with pH 1.2, 4.5, and 6.8. Moreover, the optimized samples were evaluated under stress stability conditions for determining prospects for the development of oral dosage forms.
Results: As confirmed with the results of XRD and DTA, the drugs were found to be converted into amorphous form after loading with halloysite (HNTs). The drugs were loaded in the range of ∼ 7– 9% for the four drugs, with agitation providing satisfactory and equivalent loading as compared to vacuum plus agitation based reported methods. FTIR results revealed either only weak electrostatic (verapamil HCl and flurbiprofen) or no interaction with the surface structure of the HNTs. The dissolution profiling depicted significantly retarded release of drugs with Fickian diffusion from a polydisperse system as a model that suits well for the development of oral dosage forms. HPLC-UV-based assay indicated that except furosemide (BCS class IV), the other three drugs are quite suitable for development for oral dosage forms.
Conclusion: The four drugs investigated undergo phase transformation with HNTs. While agitation is an optimum method for loading drugs with various physicochemical attributes into HNTs; solvent system, loading ratios and pH play an important role in the loading efficiency respective to the drug properties. The study supports the capability of developing HNT-based modified release oral dosage forms for drugs with high solubility.

Keywords: halloysite nanotubes, HNT, biopharmaceutics classification system, drug release kinetics, verapamil HCl, flurbiprofen, atenolol, furosemide, XRD, DTA, FTIR, SEM

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