Developing a stable aqueous enteric coating formulation with hydroxypropyl methylcellulose acetate succinate (HPMCAS-MF) and colloidal silicon dioxide as anti-tacking agent

Int J Pharm. 2018 May 5;542(1-2):108-116. doi: 10.1016/j.ijpharm.2018.02.025. Epub 2018 Feb 16.

Abstract

The purpose of this study was to use statistical design of experiments to develop a stable aqueous enteric coating formulation containing stabilizing excipients, such as polyethylene glycol that can minimize hydroxypropyl methylcellulose acetate succinate aggregation and minimize spray-nozzle clogging at elevated processing temperatures. The mechanisms of stabilization (i.e. charge stabilization and molecular interactions) were studied by performing zeta potential and FTIR studies. Electrostatic stabilization by sodium lauryl sulfate and hydrogen bonding by polyethylene glycol provided dispersion stability and yielded a stable aqueous coating formulation that prevented spray-nozzle clogging. An enteric coated tablet with better gastric resistance was obtained by incorporating fumed silica (Aerosil® R972) as the anti-tacking agent instead of talc. Dissolution testing on the riboflavin enteric coated tablets showed a good enteric release profile without releasing riboflavin in 0.1 N HCl, and completely disintegrating within 10 min in phosphate buffer (pH 6.8).

Keywords: Fourier transform infrared spectroscopy; Hydrogen bonding; PEG 4000; Principal component analysis; Spray – nozzle clogging; hydroxypropyl methylcellulose acetate succinate (HPMCAS).

MeSH terms

  • Chemistry, Pharmaceutical
  • Drug Liberation
  • Drug Stability
  • Hydrochloric Acid / chemistry
  • Methylcellulose / analogs & derivatives*
  • Methylcellulose / chemistry
  • Plasticizers / chemistry
  • Polyethylene Glycols / chemistry
  • Riboflavin / chemistry
  • Silicon Dioxide / chemistry*
  • Sodium Dodecyl Sulfate / chemistry
  • Tablets, Enteric-Coated
  • Talc / chemistry
  • Vitamin B 12 / chemistry

Substances

  • Plasticizers
  • Tablets, Enteric-Coated
  • Talc
  • Sodium Dodecyl Sulfate
  • Polyethylene Glycols
  • polyethylene glycol 4000
  • hydroxypropylmethylcellulose acetate succinate
  • Silicon Dioxide
  • Methylcellulose
  • Vitamin B 12
  • Hydrochloric Acid
  • Riboflavin