Development of Abuse-Deterrent Formulations Using Sucrose Acetate Isobutyrate

AAPS PharmSciTech. 2020 Mar 4;21(3):99. doi: 10.1208/s12249-020-01646-8.

Abstract

The objective of the present investigation was to understand the effect of sucrose acetate isobutyrate (SAIB) on abuse-deterrent properties (ADPs) of abuse-deterrent formulations (ADFs) based on Polyox™. SAIB would enhance ADPs of Polyox™-based formulations due to its glassy liquid and hydrophobic properties. Formulations were prepared by granulation followed by compression and heat curing at 90°C. The formulations were evaluated for surface morphology, hardness, manipulation in coffee grinder, particle size distribution, drug (pseudoephedrine hydrochloride) extraction in water, alcohol, 0.1 N HCl, 0.1 N NaOH at room temperature and elevated temperature using microwave and oven, syringeability and injectability, and dissolution. The heat curing of formulations significantly increased the hardness (> 490 N). Addition of SAIB imparted elasticity to formulations and decreased brittleness as indicated by lower values of work done and gradient compared to control formulations. After grinding, about 7.7-25.6% of the powder remained on the sieve (1 mm pore opening), D90 was 53.1-136.7 μm more, and Q (fraction < 500 μm) was 17.8-40.7% less in SAIB-based formulations compared to control formulations. Drug extraction between control and test intact formulations was similar. However, drug extraction was 23.9-42.5% (water), 20.6-26.1% (0.1 N HCl), and 37.4-50.6% (0.1 N NaOH) less in SAIB-based powder cured and uncured formulations compared to control formulations. Dissolution varied from 65.6 ± 4.2 to 97.6 ± 4.0% in 9 h from the formulations. In conclusion, addition of SAIB to Polyox™-based ADFs has synergistic effect on ADPs. This would further decrease potential of drug abuse/misuse by various routes.

Keywords: abuse-deterrent formulations; hardness; solvent extraction; sucrose acetate isobutyrate; syringeability and injectability.

MeSH terms

  • Abuse-Deterrent Formulations / methods*
  • Abuse-Deterrent Formulations / trends
  • Drug Compounding / methods*
  • Drug Compounding / trends
  • Drug Development / methods*
  • Drug Development / trends
  • Hardness
  • Opioid-Related Disorders / drug therapy
  • Opioid-Related Disorders / metabolism
  • Particle Size
  • Powders
  • Sucrose / administration & dosage
  • Sucrose / analogs & derivatives*
  • Sucrose / chemistry
  • X-Ray Diffraction / methods
  • X-Ray Diffraction / trends

Substances

  • Abuse-Deterrent Formulations
  • Powders
  • Sucrose
  • sucrose acetate isobutyrate