Preparation and Evaluation of Novel Supersaturated Solid Dispersion of Magnolol : Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability

Overview

Journal AAPS PharmSciTech

Publisher Springer

Specialty Pharmacology

Date 2022 Mar 25

PMID 35332440

Authors

Jing Zhao

Pan Gao

Chengqiao Mu

Jingqi Ning

Wenbin Deng

Dongxu Ji

Haowei Sun

Xiangrong Zhang

Xinggang Yang

Affiliations

Soon will be listed here.

Abstract

This article aimed to design a new type of supersaturated solid dispersion (NS-SD) loaded with Magnolol (Mag) to raise the oral bioavailability in rats. In the light of the solubility parameters, phase solubility experiments, inhibition precipitation experiment, and in vitro release experiment, Plasdone-630 (PS-630) was selected as the optimum carrier. In addition, Mag-NS-SD was prepared by adding Monoglyceride (MG) and Lecithin High Potency (LHP) into the Mag-S-SD (Mag:PS-630 = 1:3), so as to reduce the dosage of carrier and improve the release rate. Using central composite design of response surface method, the prescription was further optimized. As the optimized condition was Mag:PS-630: MG: LHP = 1:3:0.8:0.266, the drug release rate was the fastest. Besides, after 45 min, the release rate was nearly 100%. The constructed Mag-S-SD and Mag-NS-SD were characterized by powder X-ray diffraction and infrared absorption spectrum. The XRD patterns of Mag-S-SD and Mag-NS-SD indicated that all APIs were amorphous. The IR spectra of Mag-S-SD and Mag-NS-SD demonstrated the existence of hydrogen bonding in the systems. Furthermore, in vivo pharmacokinetic study in rats revealed that compared with Mag and Mag-S-SD, Mag-NS-SD significantly increased the bioavailability (the relative bioavailability was 213.69% and 142.37%, separately). In this study, Mag-NS-SD was successfully prepared, which could improve the oral bioavailability and may increase the clinical application.

Citing Articles

Navigating the Solution to Drug Formulation Problems at Research and Development Stages by Amorphous Solid Dispersion Technology.

Tripathi D, B H M, Sahoo J, Kumari J Recent Adv Drug Deliv Formul. 2023; 18(2):79-99.

PMID: 38062659 DOI: 10.2174/0126673878271641231201065151.

Supersaturation-Based Drug Delivery Systems: Strategy for Bioavailability Enhancement of Poorly Water-Soluble Drugs.

Sharma A, Arora K, Mohapatra H, Sindhu R, Bulzan M, Cavalu S Molecules. 2022; 27(9).

PMID: 35566319 PMC: 9101434. DOI: 10.3390/molecules27092969.

References

Lee B, Choi S, Kim H, Park S, Rhim H, Kim H . Gintonin absorption in intestinal model systems. J Ginseng Res. 2018; 42(1):35-41. PMC: 5766688. DOI: 10.1016/j.jgr.2016.12.007. View

Wenlock M, Austin R, Barton P, Davis A, Leeson P . A comparison of physiochemical property profiles of development and marketed oral drugs. J Med Chem. 2003; 46(7):1250-6. DOI: 10.1021/jm021053p. View

Mu H, Holm R, Mullertz A . Lipid-based formulations for oral administration of poorly water-soluble drugs. Int J Pharm. 2013; 453(1):215-24. DOI: 10.1016/j.ijpharm.2013.03.054. View

Brouwers J, Brewster M, Augustijns P . Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability?. J Pharm Sci. 2009; 98(8):2549-72. DOI: 10.1002/jps.21650. View

Xu S, Dai W . Drug precipitation inhibitors in supersaturable formulations. Int J Pharm. 2013; 453(1):36-43. DOI: 10.1016/j.ijpharm.2013.05.013. View

Gao P, Rush B, Pfund W, Huang T, Bauer J, Morozowich W . Development of a supersaturable SEDDS (S-SEDDS) formulation of paclitaxel with improved oral bioavailability. J Pharm Sci. 2003; 92(12):2386-98. DOI: 10.1002/jps.10511. View

Huang Y, Dai W . Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B. 2015; 4(1):18-25. PMC: 4590721. DOI: 10.1016/j.apsb.2013.11.001. View

Urbanetz N, Lippold B . Solid dispersions of nimodipine and polyethylene glycol 2000: dissolution properties and physico-chemical characterisation. Eur J Pharm Biopharm. 2004; 59(1):107-18. DOI: 10.1016/j.ejpb.2004.08.005. View

Tsunashima D, Yamashita K, Ogawara K, Sako K, Higaki K . Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method. J Pharm Pharmacol. 2016; 68(3):316-23. DOI: 10.1111/jphp.12515. View

11.

Xia D, Yu H, Tao J, Zeng J, Zhu Q, Zhu C . Supersaturated polymeric micelles for oral cyclosporine A delivery: The role of Soluplus-sodium dodecyl sulfate complex. Colloids Surf B Biointerfaces. 2016; 141:301-310. DOI: 10.1016/j.colsurfb.2016.01.047. View

12.

Chavan R, Modi S, Bansal A . Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib. Int J Pharm. 2015; 495(1):374-384. DOI: 10.1016/j.ijpharm.2015.09.011. View

13.

Agarwal V, Siddiqui A, Ali H, Nazzal S . Dissolution and powder flow characterization of solid self-emulsified drug delivery system (SEDDS). Int J Pharm. 2008; 366(1-2):44-52. DOI: 10.1016/j.ijpharm.2008.08.046. View

14.

Lin M, Chen M, Chen T, Chang H, Chou T . Magnolol ameliorates lipopolysaccharide-induced acute lung injury in rats through PPAR-γ-dependent inhibition of NF-kB activation. Int Immunopharmacol. 2015; 28(1):270-8. DOI: 10.1016/j.intimp.2015.05.051. View

15.

Pacult J, Rams-Baron M, Chrzaszcz B, Jachowicz R, Paluch M . Effect of Polymer Chain Length on the Physical Stability of Amorphous Drug-Polymer Blends at Ambient Pressure. Mol Pharm. 2018; 15(7):2807-2815. DOI: 10.1021/acs.molpharmaceut.8b00312. View

16.

Li Y, Lu M, Wu C . PVP VA64 as a novel release-modifier for sustained-release mini-matrices prepared via hot melt extrusion. Drug Deliv Transl Res. 2017; 8(6):1670-1678. DOI: 10.1007/s13346-017-0437-9. View

17.

Yu H, Xia D, Zhu Q, Zhu C, Chen D, Gan Y . Supersaturated polymeric micelles for oral cyclosporine A delivery. Eur J Pharm Biopharm. 2013; 85(3 Pt B):1325-36. DOI: 10.1016/j.ejpb.2013.08.003. View

18.

Kuentz M, Holm R, Elder D . Methodology of oral formulation selection in the pharmaceutical industry. Eur J Pharm Sci. 2015; 87:136-63. DOI: 10.1016/j.ejps.2015.12.008. View

19.

Forster A, Hempenstall J, Tucker I, Rades T . Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis. Int J Pharm. 2001; 226(1-2):147-61. DOI: 10.1016/s0378-5173(01)00801-8. View

20.

Bloch D, Elegakey M, SPEISER P . Solid dispersion of chlorthalidone in urea phase diagram and dissolution characteristics. Pharm Acta Helv. 1982; 57(8):231-5. View

21.

Zhu C, Gong S, Ding J, Yu M, Ahmad E, Feng Y . Supersaturated polymeric micelles for oral silybin delivery: the role of the Soluplus-PVPVA complex. Acta Pharm Sin B. 2019; 9(1):107-117. PMC: 6361729. DOI: 10.1016/j.apsb.2018.09.004. View