Formulation of metoclopramide HCl gastroretentive film and in vitro- in silico prediction using Gastroplus® PBPK software

Abstract

The new trends in pharmaceutical studies focus on targeting drug delivery and computer software that help in the body environment simulation, such as Gastroplus® software. The interest of this study is to prepare a gastroretentive film of metoclopramide HCl (MTC) that was followed by applying the in silico approach to estimate the in vivo prepared formulations. The films were prepared from HPMC E5 and sodium alginate polymers as primary polymers with the aid of secondary polymers. The sodium alginate high proportions films showed instant and long floating duration reaching 24 h but with variable folding endurance. Moreover, sodium alginate films with their secondary polymers carbopol and HPMC E5 slowed the release of MTC. The floating and slow-release patterns assessed the gastroretentive properties of sodium alginate films and were further examined by a mucoadhesive study that guaranteed mucosal adhesion, and the film's FESEM images showed similar top morphology, but different side view structures. Last, the pharmacokinetic profile of selected films that approached the gastroretentive properties was in silico predicted depending on in vitro release study and floating duration employing the physiological-based pharmacokinetic model in Gastroplus® software. The model determines this prediction found successfully of intravenous and immediate oral release tablets (10 and 30 mg) of MTC. The simulation showed a high amount of MTC retained for long periods in the stomach to Sod.Alginate-3, Sod.Alginate-8, and Sod.Alginate-10 films (films of secondary polymers carbopol and HPMC E5) aid in reaching the optimum site of absorption jejunum 1 due to the slow MTC release.

Keywords: Gastroplus®; Gastroretentive films; Metoclopramide HCl; PBPK.

Fig. 1

In vitro MTC release for different films where Figure A represents HPMC E5 films with Carbopol® 934 NF, Figure B represents sodium alginate with Carbopol® 934 NF films, Figure C shows the sodium alginate with HPMC K4M films, and Figure D exhibits sodium alginate with HPMC E5 film as this study was done in triplicate in 900 ml acidic media 0.1 N HCl pH 1.2.

Fig. 2

FESEM picture of the films. (A and B) top and cross-section of HPMC E5-2. (C and D) top and cross-section of Sod. Alginate-9. (E and F) top and cross-section of Sod. Alginate-3. (G and H) top and cross-section of Sod. Alginate-8. (I and J) top and cross-section of Sod. Alginate-10. Images (A, E, and G) in the left column were scaled against 200 nm, and images (C and I) in the left column were scaled against 500 nm, whereas images in the right column were scaled against 10 µm.

Fig. 3

A and B are Gastroplus® figures as the dotted line represents the observed data while the solid represents the MTC predicted values after IV and oral immediate-release tablet administration of 10 mg, respectively. Figure C represents the predicted model for oral immediate-release 30 mg.

Fig. 4

Predected plasma concentration–time curves of selected films.

Fig. 5

Predicting data A- The regional absorption of the 10 mg MTC selected gastroretentive films. B- The MTC amount retained in the stomach for 24 h of each MTC gstroretentive film. C- The MTC amount retained in the stomach for each MTC gstroretentive film in the first 2 h of simulated time. These data were obtained from Gastroplus® software (version 9.8, SimulationPlus Inc., Lancaster, CA, USA).