TY - JOUR

T1 - Mechanisms of Drug Solubility Enhancement Induced by β-Lactoglobulin-Based Amorphous Solid Dispersions

AU - Zhuo, Xuezhi

AU - Sener, Zeyneb

AU - Kabedev, Aleksei

AU - Zhao, Min

AU - Arnous, Anis

AU - Leng, Donglei

AU - Foderà, Vito

AU - Löbmann, Korbinian

N1 - Funding Information: The China Scholarship Council (CSC, No. 201908210313) is acknowledged for financial support for X.Z. VILLUM FONDEN by the Villum Young Investigator Grant “Protein Superstructure as Smart Biomaterials (ProSmart)” 2018–2023 (Project Number: 19175) and Novo Nordisk Foundation (Project NNF 0065260) are acknowledged for supporting the project. Arla Foods Ingredients Group P/S is thanked for providing the samples of Lacprodan BLG Pharma Grade. Publisher Copyright: © 2023 American Chemical Society

PY - 2023

Y1 - 2023

N2 - Protein-based amorphous solid dispersions (ASDs) have emerged as a promising approach for enhancing solubility in comparison to crystalline drugs. The dissolution behavior of protein-based amorphous solid dispersions (ASDs) was investigated in various pH media. ASDs of four poorly soluble model drugs with acidic (furosemide and indomethacin), basic (carvedilol), and neutral (celecoxib) properties were prepared by spray drying at 30 wt % drug loading with the protein β-lactoglobulin (BLG). The effect of spray-dried BLG (SD-BLG) solubility and protein binding ability with dissolved drugs in solution were investigated to retrieve the mechanisms governing the improvement of drug solubility from the BLG-based ASDs. Powder dissolution results showed that all ASDs obtained a higher maximum concentration (Cmax) compared to the respective pure crystalline drugs. It was found that the solubility increase of the drugs from the ASDs was to a large extent dependent on the solubility of the pure SD-BLG at the investigated pH values (low solubility at pH near the isoelectric point (pI) of BLG). Furthermore, drug-protein interactions in a solution were observed, in particular at pH values where the drugs were neutral. These drug-protein interactions also resulted, to some extent, in the stabilization of the drug in supersaturation.

AB - Protein-based amorphous solid dispersions (ASDs) have emerged as a promising approach for enhancing solubility in comparison to crystalline drugs. The dissolution behavior of protein-based amorphous solid dispersions (ASDs) was investigated in various pH media. ASDs of four poorly soluble model drugs with acidic (furosemide and indomethacin), basic (carvedilol), and neutral (celecoxib) properties were prepared by spray drying at 30 wt % drug loading with the protein β-lactoglobulin (BLG). The effect of spray-dried BLG (SD-BLG) solubility and protein binding ability with dissolved drugs in solution were investigated to retrieve the mechanisms governing the improvement of drug solubility from the BLG-based ASDs. Powder dissolution results showed that all ASDs obtained a higher maximum concentration (Cmax) compared to the respective pure crystalline drugs. It was found that the solubility increase of the drugs from the ASDs was to a large extent dependent on the solubility of the pure SD-BLG at the investigated pH values (low solubility at pH near the isoelectric point (pI) of BLG). Furthermore, drug-protein interactions in a solution were observed, in particular at pH values where the drugs were neutral. These drug-protein interactions also resulted, to some extent, in the stabilization of the drug in supersaturation.

KW - amorphous solid dispersion

KW - binding ability

KW - dissolution

KW - supersaturation

KW - β-lactoglobulin

U2 - 10.1021/acs.molpharmaceut.3c00577

DO - 10.1021/acs.molpharmaceut.3c00577

M3 - Journal article

C2 - 37669430

AN - SCOPUS:85171788442

VL - 20

SP - 5206

EP - 5213

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 10

ER -