Enhanced Stability and Improved Oral Absorption of Enzalutamide with Self-Nanoemulsifying Drug Delivery System.

The purpose of this study is to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral absorption of poorly water-soluble enzalutamide (ENZ). Considering the rapid recrystallization of the drug, based on solubility and crystallization tests in various oils, surfactants and co-surfactants, Labrafac PG 10%, Solutol HS15 80%, and Transcutol P 10%, which showed the most stable particle size and polydispersity index (PDI) without drug precipitation, were selected as the optimal SNEDDS formulation. The optimized SNEDDS formulation showed excellent dissolution profiles for all the drugs released at 10 min of dissolution due to the increased surface area with a small particle size of approximately 16 nm. Additionally, it was confirmed to be stable without significant differences in physical and chemical properties for 6 months under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) and stressed conditions (60 ± 2 °C). Associated with the high dissolutions of ENZ, pharmacokinetic parameters were also greatly improved. Specifically, the AUC was 1.9 times higher and the Cmax was 1.8 times higher than those of commercial products (Xtandi® soft capsule), resulting in improved oral absorption. Taken together with the results mentioned above, the SNEDDS could be an effective tool as a formulation for ENZ and other similar drugs.

Enhanced Stability and Compatibility of Montelukast and Levocetirizine in a Fixed-Dose Combination Monolayer Tablet.

The purpose of this study was to enhance the stability of montelukast and levocetirizine for the development of a fixed-dose combination (FDC) monolayer tablet. To evaluate the compatibility of montelukast and levocetirizine, a mixture of the two drugs was prepared, and changes in the appearance characteristics and impurity content were observed in a dry oven at 60 °C. Excipients that contributed minimally to impurity increases were selected to minimize drug interactions. Mannitol, microcrystalline cellulose, croscarmellose sodium, hypromellose, and sodium citrate were chosen as excipients, and montelukast-levocetirizine FDC monolayer tablets were prepared by wet granulating the two drugs separately. A separate granulation of montelukast and levocetirizine, along with the addition of sodium citrate as a pH stabilizer, minimized the changes in tablet appearance and impurity levels. The prepared tablets demonstrated release profiles equivalent to those of commercial products in comparative dissolution tests. Subsequent stability testing at 40 ± 2 °C and 75 ± 5% RH for 6 months confirmed that the drug content, dissolution rate, and impurity content met the specified acceptance criteria. In conclusion, the montelukast-levocetirizine FDC monolayer tablet developed in this study offers a potential alternative to commercial products.

The Impact of Polymers on Enzalutamide Solid Self-Nanoemulsifying Drug Delivery System and Improved Bioavailability.

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.