Development and Characterization of Olaparib-Loaded Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Pharmaceutical Applications

AAPS PharmSciTech. 2024 Sep 24;25(7):221. doi: 10.1208/s12249-024-02927-2.

Abstract

This study aims to enhance the solubility of Olaparib, classified as biopharmaceutical classification system (BCS) class IV due to its low solubility and bioavailability using a solid self-nanoemulsifying drug delivery system (S-SNEDDS). For this purpose, SNEDDS formulations were created using Capmul MCM as the oil, Tween 80 as the surfactant, and PEG 400 as the co-surfactant. The SNEDDS formulation containing olaparib (OLS-352), selected as the optimal formulation, showed a mean droplet size of 87.0 ± 0.4 nm and drug content of 5.53 ± 0.09%. OLS-352 also demonstrated anticancer activity against commonly studied ovarian (SK-OV-3) and breast (MCF-7) cancer cell lines. Aerosil® 200 and polyvinylpyrrolidone (PVP) K30 were selected as solid carriers, and S-SNEDDS formulations were prepared using the spray drying method. The drug concentration in S-SNEDDS showed no significant changes (98.4 ± 0.30%, 25℃) with temperature fluctuations during the 4-week period, demonstrating improved storage stability compared to liquid SNEDDS (L-SNEDDS). Dissolution tests under simulated gastric and intestinal conditions revealed enhanced drug release profiles compared to those of the raw drug. Additionally, the S-SNEDDS formulation showed a fourfold greater absorption in the Caco-2 assay than the raw drug, suggesting that S-SNEDDS could improve the oral bioavailability of poorly soluble drugs like olaparib, thus enhancing therapeutic outcomes. Furthermore, this study holds significance in crafting a potent and cost-effective pharmaceutical formulation tailored for the oral delivery of poorly soluble drugs.

Keywords: BCS class IV; bioavailability; olaparib; solid SNEDDS; spray drying.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Biological Availability*
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Drug Carriers / chemistry
  • Drug Compounding / methods
  • Drug Delivery Systems* / methods
  • Drug Liberation
  • Drug Stability
  • Emulsions* / chemistry
  • Humans
  • MCF-7 Cells
  • Nanoparticles / chemistry
  • Particle Size
  • Phthalazines* / administration & dosage
  • Phthalazines* / chemistry
  • Phthalazines* / pharmacokinetics
  • Phthalazines* / pharmacology
  • Piperazines* / administration & dosage
  • Piperazines* / chemistry
  • Piperazines* / pharmacokinetics
  • Polyethylene Glycols / chemistry
  • Solubility*
  • Surface-Active Agents / chemistry

Substances

  • Piperazines
  • olaparib
  • Phthalazines
  • Emulsions
  • Antineoplastic Agents
  • Surface-Active Agents
  • Drug Carriers
  • Polyethylene Glycols