TY - JOUR

T1 - A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches

T2 - A Case Study with Rifaximin

AU - Zhuo, Xuezhi

AU - Margrethe Brekstad Kjellin, Maud

AU - Schaal, Zarah

AU - Zhang, Tengyu

AU - Löbmann, Korbinian

AU - Leng, Donglei

N1 - Funding Information: X.Z. would like to thank the China Scholarship Council (CSC No: 201908210313) for financial support. Arla Foods Ingredients Group P/S is thanked for providing the samples of Lacprodan BLG Pharma Grade. ®

PY - 2023

Y1 - 2023

N2 - Amorphous solid dispersions (ASDs) based on proteins as co-formers have previously shown promising potential to improve the solubility and bioavailability of poorly water-soluble drugs. In particular, whey proteins have shown to be promising co-formers and amorphous stabilizers in ASD formulations, including at high drug loading. In this study, the feasibility of the whey protein β-lactoglobulin (BLG) as a co-former in ASDs was compared to the more traditional ASD co-formers based on synthetic polymers (hydroxypropyl methylcellulose acetate succinate and Eudragit® L) as well as to a nanocrystalline formulation. The poorly water-soluble drug rifaximin (RFX) was chosen as the model drug. All drug/co-former formulations were prepared as fully amorphous ASDs by spray drying at 50% (w/w) drug loading. The BLG-based ASD had the highest glass transition temperature and showed a faster dissolution rate and higher drug solubility in three release media with different pH values (1.2, 4.5, and 6.5) compared to the polymer-based ASDs and the nanocrystalline RFX. In conclusion, BLG is a promising co-former and amorphous stabilizer of RFX in ASD formulations, superior to the selected polymer-based ASD systems or the nanocrystalline formulation.

AB - Amorphous solid dispersions (ASDs) based on proteins as co-formers have previously shown promising potential to improve the solubility and bioavailability of poorly water-soluble drugs. In particular, whey proteins have shown to be promising co-formers and amorphous stabilizers in ASD formulations, including at high drug loading. In this study, the feasibility of the whey protein β-lactoglobulin (BLG) as a co-former in ASDs was compared to the more traditional ASD co-formers based on synthetic polymers (hydroxypropyl methylcellulose acetate succinate and Eudragit® L) as well as to a nanocrystalline formulation. The poorly water-soluble drug rifaximin (RFX) was chosen as the model drug. All drug/co-former formulations were prepared as fully amorphous ASDs by spray drying at 50% (w/w) drug loading. The BLG-based ASD had the highest glass transition temperature and showed a faster dissolution rate and higher drug solubility in three release media with different pH values (1.2, 4.5, and 6.5) compared to the polymer-based ASDs and the nanocrystalline RFX. In conclusion, BLG is a promising co-former and amorphous stabilizer of RFX in ASD formulations, superior to the selected polymer-based ASD systems or the nanocrystalline formulation.

KW - amorphous solid dispersion

KW - dissolution

KW - nanocrystal

KW - polymer

KW - β-lactoglobulin

U2 - 10.3390/pharmaceutics15010126

DO - 10.3390/pharmaceutics15010126

M3 - Journal article

C2 - 36678757

AN - SCOPUS:85146579370

VL - 15

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 1

M1 - 126

ER -