Investigation of Stabilized Amorphous Solid Dispersions to Improve Oral Olaparib Absorption

• Main Authors: Taehan Yun (Author), Sumin Lee (Author), Seowan Yun (Author), Daeyeong Cho (Author), Kyuho Bang (Author), Kyeongsoo Kim (Author)
• Format: Book
• Published: MDPI AG, 2024-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

In this study, we investigated the formulation of stable solid dispersions to enhance the bioavailability of olaparib (OLA), a therapeutic agent for ovarian cancer and breast cancer characterized as a BCS class IV drug with low solubility and low permeability. Various polymers were screened based on solubility tests, and OLA-loaded solid dispersions were prepared using spray drying. The physicochemical properties of these dispersions were investigated via scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier Transform Infrared Spectroscopy (FT-IR). Subsequent dissolution tests, along with assessments of morphological and crystallinity changes in aqueous solutions, led to the selection of a hypromellose (HPMC)-based OLA solid dispersion as the optimal formulation. HPMC was effective at maintaining the supersaturation of OLA in aqueous solutions and exhibited a stable amorphous state without recrystallization. In an in vivo study, this HPMC-based OLA solid dispersion significantly enhanced bioavailability, increasing AUC_0-24 by 4.19-fold and C_max by more than 10.68-fold compared to OLA drug powder (crystalline OLA). Our results highlight the effectiveness of HPMC-based solid dispersions in enhancing the oral bioavailability of OLA and suggest that they could be an effective tool for the development of oral drug formulations.

Item Description

10.3390/pharmaceutics16070958
1999-4923