Development of novel gastroretentive salbutamol sulfate-loaded sodium alginate-pectin bubble beads prepared by co-axial needle air-injection method and in vivo clinical evaluation by ultrasound studies

Eur J Pharm Sci. 2018 Sep 15:122:359-373. doi: 10.1016/j.ejps.2018.07.019. Epub 2018 Jul 12.

Abstract

In the present study, the salbutamol sulfate-loaded sodium alginate-pectin (SS-loaded SA-PEC) bubble beads have been optimized and evaluated for drug loading, in vitro drug release, in vivo floating behavior in the stomach, etc. Nine batches (F1-F9) of bubble beads with different SA and PEC contents were prepared by novel co-axial needle air-injection method and related to their percent drug loading efficiency (%DLE) and percent drug release at 4 h (%R4h) as response factors. The multivariate analysis has shown the effect of SA/PEC ratio, total polymer content, as well as their interaction on %DLE and %R4h. In the quantitative modeling, the satisfactory adjustment of the linear models (along with interaction terms) with the experimental data for both %DLE and %R4h has confirmed the findings of the multivariate analysis. The optimized SS-loaded SA-PEC bubble beads based on 2D (contours), 3D, desirability, and overlay plots has exhibited %DLE of 87.35 ± 2.48% (n = 3 and error = 2.94%) and %R4h of 85.79 ± 2.98% (n = 3 and error = 0.25%). The in vitro drug release studies have shown almost complete (≥85%) SS release from all the batches within 4-6 h in simulated gastric fluid (SGF) pH 1.2. The in vivo clinical findings by ultrasound studies have shown excellent floatation (>6 h) behavior of bubble beads in the upper gastrointestinal tract (GIT) and efficient stomach-specific gastroretention.

Keywords: Air or gas; Bubbles; Drug delivery; Floating beads; Needles; Optimization; Ultrasound imaging.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists* / administration & dosage
  • Adrenergic beta-2 Receptor Agonists* / chemistry
  • Albuterol* / administration & dosage
  • Albuterol* / chemistry
  • Alginates* / administration & dosage
  • Alginates* / chemistry
  • Drug Delivery Systems*
  • Drug Liberation
  • Gastrointestinal Tract / diagnostic imaging
  • Glucuronic Acid / administration & dosage
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / administration & dosage
  • Hexuronic Acids / chemistry
  • Humans
  • Pectins* / administration & dosage
  • Pectins* / chemistry
  • Ultrasonography

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Alginates
  • Hexuronic Acids
  • Pectins
  • Glucuronic Acid
  • Albuterol