Using Acetone/Water Binary Solvent to Enhance the Stability and Bioavailability of Spray Dried Enzalutamide/HPMC-AS Solid Dispersions

Abstract

We demonstrated a facile approach, by adjusting the solvent ratio of water/acetone binary mixture, to alter the intermolecular interactions between Enzalutamide (ENZ) and hydroxypropyl methylcellulose acetate succinate (HPMC-AS) for spray drying process, which can be readily implemented to produce spray-dried dispersions (SDD) with enhanced stability and bioavailability.The prepared SDD of ENZ/HPMC-AS were examined systematically in terms of particle size, morphology, dissolution, solubility, stability, and bioavailability. Our results show that the introduction of water (up to 30% volume fraction) can effectively reduce the hydrodynamic diameter of HPMC-AS from approximately 220 nm to 160 nm (a reduction of c.a. 20%), which increases the miscibility of the drug and polymer, delaying or inhibiting the crystallization of ENZ during the spray drying process, resulting in a homogeneous amorphous phase. The benefits of using acetone/water binary mixture were subsequently evidenced by an increased specific surface area, improved dissolution profile and relative bioavailability, enhanced stability, and elevated drug release rate. This fundamental finding underpins the great potential of using binary mixture for spray drying process to process active pharmaceutical ingredients (APIs) that are otherwise challenging to handle.

Cocrystal and Coamorphous Solid Forms of Enzalutamide with Saccharin: Structural Characterization and Dissolution Studies

“…Additional insights into the structural features of the cocrystal and coamorphous forms of Enz with Schr were gained from the vibrational spectroscopy analysis. As Figure illustrates, the FT-IR spectrum of the parent Enz contains the main bands at 3434 cm –1 (N–H stretching), 3091 cm –1 (C–H aromatic stretching), 2947 cm –1 (C–H aliphatic stretching), 2234 cm –1 (CN stretching), and 1771 and 1666 cm –1 (CO stretching) in accord with the literature data . Although amorphization of Enz resulted in the broadening of the peaks, no significant shift in peak positions was observed in the amide and fingerprint regions, indicating minor alteration of molecular arrangement compared to the crystalline material.…”

“…As Figure 6 illustrates, the FT-IR spectrum of the parent Enz contains the main bands at 3434 cm −1 (N−H stretching), 3091 cm −1 (C− H aromatic stretching), 2947 cm −1 (C−H aliphatic stretching), 2234 cm −1 (C�N stretching), and 1771 and 1666 cm −1 (C� O stretching) in accord with the literature data. 13 Although amorphization of Enz resulted in the broadening of the peaks, 71 no significant shift in peak positions was observed in the amide and fingerprint regions, indicating minor alteration of molecular arrangement compared to the crystalline material. The most prominent peaks in the Schr spectrum are the following: 3402 and 3094 cm −1 (N−H stretching), 2975 cm −1 (C−H aromatic stretching), 1718 cm −1 (C�O stretching), and 1336 and 1177 cm −1 (asymmetric and symmetric SO 2 stretching) 72−74 (Figure 6).…”

“…However, due to the recommended dose of 160 mg, patients have to take the medicine four times a day, which may lead to inconsistency when it comes to medication adherence. To increase the drug loading and simultaneously improve its dissolution performance, supersaturating delivery systems have been developed by incorporating amorphous enzalutamide into various polymer matrices to form amorphous solid dispersions. − A nanocarrier based on graphene oxide has been applied to dispose of the solubility problem and to create a complex composition for the intravenous administration of Enz . In addition, Volkova et al have shown that even though the aqueous solubility of Enz can be substantially improved by polymers and cyclodextrins, these excipients have a detrimental effect on the permeability of the drug compound …”

Hydrogen-Bonded Networks in Acetone-Alcohol Binary Mixture: Molecular Dynamics Study

“…Molecular Dynamics (MD) simulations are used widely to study the structural and dynamical properties of multicomponent liquid mixtures [10][11][12][13]. However, not many studies have been conducted on acetone-alcohol binary mixtures, especially for higher alcohols.…”

Thermodynamics and Intermolecular Interactions of Nicotinamide in Neat and Binary Solutions: Experimental Measurements and COSMO-RS Concentration Dependent Reactions Investigations

“…Binary solvents have been successfully applied in various areas, including materials engineering, green chemistry technologies, and pharmacy. Some recently published reports provide interesting applications, for example a bioavailability enhancement of enzalutamide via spray drying technique using acetone-water binary solvents [ 33 ], lignin extraction from waste sawdust [ 34 ], the application of anti-solvent effects in perovskite solar cell manufacturing [ 35 , 36 , 37 ], and the supercritical fluid extraction of various phytochemicals such as phenolic compounds [ 38 ] and alkaloids [ 39 ]. The above mentioned applications demonstrate the usefulness of both solubility increase (co-solvation) and solubility decrease (anti-solvation).…”