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

Abstract

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.

Drug Delivery Nano-Platforms for Advanced Cancer Therapy

“…For example in work of Shi et al HNTs covered with 3-amino-propyl-triethoxysilane (APTES) were given as an antisense oligonucleotide to the HeLa cells [148]. Some researches describe the systematic investigations of HNTs to fabricate the oral drug delivery platform on the base of commercially available drugs including resveratrol, paclitaxel, verapamil [132,[149][150][151][152][153][154][155][156]. Recently, Lazzara et al conducted an extensive in vitro toxicity and genotoxicity analysis of hal-loysite nanotubes from various sources in HeLa, CHO and HepG2 cell lines and concluded that halloysite has good biocompatibility at low doses and short exposure times [157].…”

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling

“…The samples were attached to aluminum stubs with double side adhesive carbon tape, gold coated (250 0A JFC-1500 JEOL), and sputter coater. SEM photographs were recorded and examined (Husain et al, 2021).…”

A Novel Efficient Piscine Oral Nano-Vaccine Delivery System: Modified Halloysite Nanotubes (HNTs) Preventing Streptococcosis Disease in Tilapia (Oreochromis sp.)

“…In addition, due to their hollow shape, they can promote encapsulated efficacy and can also help to protect susceptible biological molecules through the host’s delivering tract [ 17 ]. So far, a variety of advantageous applications based on native HNTs has been researched, including biologic nanocarriers [ 18 , 19 , 20 , 21 , 22 ]. Nevertheless, several studies have suggested that functionalized HNTs manufactured by grafting their surfaces with some substances can enhance their desirable characteristics for use in drug delivery systems [ 23 , 24 ].…”