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

• Published in: AAPS PharmSciTech 2024-09, Vol.25 (7), p.221, Article 221
• Main Authors: Shin, Yuseon, Kim, Mikyung, Kim, Chaeyeon, Jeon, Hyewon, Koo, Jain, Oh, Jimin, Shin, Soyoung, Youn, Yu Seok, Lim, Chaemin, Oh, Kyung Taek
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedicine; Biotechnology; 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; Pharmacology/Toxicology; Pharmacy; Phthalazines - administration & dosage; Phthalazines - chemistry; Phthalazines - pharmacokinetics; Phthalazines - pharmacology; Piperazines - administration & dosage; Piperazines - chemistry; Piperazines - pharmacokinetics; Polyethylene Glycols - chemistry; Research Article; Solubility; Surface-Active Agents - chemistry
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-024-02927-2

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. Graphical Abstract