Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies

Publication: International Journal of Molecular Sciences


This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release agent for Verapamil HCl (BCS Class-I). Drug-loaded halloysite was prepared and tablet formulations were designed by varying amount of hydroxy propyl methyl cellulose (HPMC K4M). Physical characterization was carried out using SEM, FTIR, and DSC. Tabletability profiles were evaluated using USP1062 guidelines. Drug release kinetics were studied, and physiologically based pharmacokinetic (PBPK) modeling was performed. Compressed tablets possess satisfactory yield pressure of 625 MPa with adequate hardness and disintegration within 30 min. The initial release of the drug was due to surface drug on tablets, while the prolonged release at later time points (around 80 % drug release at 12 h) were due to halloysite loading. The FTIR spectra exhibited electrostatic attraction between the positively charged drug and the negatively charged Si-O-Si functional group of halloysite, while the thermogram showed Verapamil HCl melting point at ~146 °C with enthalpy change of −126.82 J/g. PBPK modeling exhibited PK parameters of optimized matrix formulation (VER-HNT3%) comparable to in vivo data. The study effectively demonstrated the potential of prepared biocomposite matrix as a commercially viable oral release modifying agent for highly soluble drugs.

By Tazeen Husain, Muhammad Harris Shoaib, Farrukh Rafiq Ahmed, Rabia Ismail Yousuf, Fahad Siddiqui, Muhammad Talha Saleem, Sadaf Farooqi, Sabahat Jabeen