Development of Novel Indole-3-Aldehyde-Loaded Gastro-Resistant Spray-Dried Microparticles for Postbiotic Small Intestine Local Delivery

J Pharm Sci. 2018 Sep;107(9):2341-2353. doi: 10.1016/j.xphs.2018.04.023. Epub 2018 Apr 30.

Abstract

Considering the recent evidence on the therapeutic potential of postbiotics, this study focused on 2 main goals: (1) to develop an enteric microparticle (MP) formulation for intestinal localized delivery of indole-3-aldehyde (3-IAld) (a microbial-derived metabolite produced by the host's lactobacilli during the catabolic pathway of tryptophan) and (2) to provide support in the employment of spray-drying as innovative one-step manufacturing technique for enteric products. For this purpose, special attention was taken in the knowledge of the influence of equipment setup and feedstock properties on MP enteric behavior. Eudragit® S100 and L100 and ethyl cellulose were used as wall materials and NaOH and ethanol solutions as solvent systems. 3-IAld loading was maintained at 10% w/w. As postulated, feedstock properties influenced spray-drying regime. In addition, they prevailed over other spray-drying process factors in determining MP enteric behavior. Albeit the high buckling regime that produced crumped particles, gastro resistance was obtained by spray-drying 2:1 Eudragit® S100:L100 with 30% w/w ethyl cellulose in ethanol solution. These results support the use of spray-drying as a method for manufacturing gastro-resistant MP. The obtained 3-IAld-loaded enteric MP will be useful to investigate novel postbiotic-based treatments in different therapeutic areas.

Keywords: controlled release; dissolution; drug delivery; microencapsulation; spray-drying.

MeSH terms

  • Cellulose / administration & dosage
  • Cellulose / analogs & derivatives
  • Cellulose / chemistry
  • Cellulose / pharmacokinetics
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Drug Development / methods*
  • Drug Liberation*
  • Indoles / administration & dosage
  • Indoles / chemistry*
  • Indoles / pharmacokinetics
  • Intestine, Small*
  • Microspheres*
  • Particle Size
  • Polymethacrylic Acids / administration & dosage
  • Polymethacrylic Acids / chemistry
  • Polymethacrylic Acids / pharmacokinetics
  • Stomach

Substances

  • Delayed-Action Preparations
  • Indoles
  • Polymethacrylic Acids
  • methylmethacrylate-methacrylic acid copolymer
  • indole-3-carbaldehyde
  • ethyl cellulose
  • Cellulose