Formulation development, characterization, and mechanistic PBPK modeling of metoclopramide loaded halloysite nanotube (HNT) based drug-in-adhesive type transdermal drug delivery system

Abstract

Abstract Metoclopramide is an antiemetic agent prescribed for motion sickness, cancer chemotherapy, and pregnancy. The present work aimed to design a metoclopramide-loaded halloysite nanotubes (HNTs) drug-in-adhesive transdermal drug delivery system. Four formulations F1, F2, and F3 with different ratios of HNTs to metoclopramide and a F4 without HNTs were developed using acrylic adhesive DURO-TAK 387–2510 by the solvent casting method. These formulated patches were thoroughly evaluated and in-vitro release and permeation studies were performed. The optimized formulation was analyzed using skin irritation, SEM, DSC, and FTIR studies. The GASTROPLUS TCAT model was used to predict the in-vivo performance. HNT-based formulations exhibited controlled drug release, achieving approximately 60% in 4 h, compared to over 80% release in the same period from the formulation without HNT. The optimized formulation (F3) demonstrated a lag time of 1.802 h with a flux of 0.103 mg/cm2/hr. The shelf life was 19.279 months at 5 ± 3 °C. The C max , T max , AUC t, and AUC inf were predicted as 40.84 ng/mL, 6.32 h, 561.51 ng/mL×h and 599.61 ng/mL×h for a 30 mg patch. The study demonstrated that metoclopramide can be effectively loaded into HNTs and proved safe and effective in drug-in-adhesive type transdermal systems using HNTs as a drug carrier.

Keywords

• Transdermal, Halloysite nanotube
• Metoclopramide
• DURO-TAK 387–2510
• Drug-in-adhesive
• Physiological based pharmacokinetics (PBPK)