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

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.

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Materials

Olaparib was sourced from MedKoo Biosciences, Inc. (Morrisville, NC, USA). 1-Butanol, tetraglycol, Pluronic L121, P123, F127, cottonseed oil, Span 80, and PVP K30 (average molecular weight 40-kDa) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Coconut oil, triacetin, isopropyl myristate, soybean oil, Tween 80, Span 80, Span 20, and mineral oil were acquired from Daejung Chemicals Co. (Siheung, South Korea). Peceol, Labrafil M 1994 CS, Labrafil M 2125, Labrasol, Transcutol P, Capryol 90, and Labrafac™ Lipophile WL 1349 were obtained from Gattefossé (Saint-Priest Cedex, France). Capmul MCM and Captex 355 were gifted from Abitec Corporation (Columbus, OH, USA). Propylene glycol, Tween 20, olive oil, and high-performance liquid chromatography (HPLC)-grade ethanol (EtOH) were purchased from Duksan Pure Chemical (Ansan, South Korea). Polyethylene glycol (PEG) 200, 400, 600, oleic acid, and Tween 60 were obtained from Samchun Pure Chemi-cal (Gyeonggi-Do, South Korea). Colloidal silica (Aerosil® 200 Pharma) came from Evonik industries AG (Essen, Germany). HPLC-grade acetonitrile was purchased from Honeywell Burdick &  Jackson® (Muskegon, MI, USA). All other chemicals used were of analytical grade.

Shin, Y., Kim, M., Kim, C. et al. Development and Characterization of Olaparib-Loaded Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Pharmaceutical Applications. AAPS PharmSciTech 25, 221 (2024). https://doi.org/10.1208/s12249-024-02927-2