A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin
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,...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/126 |
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| author | Xuezhi Zhuo Maud Margrethe Brekstad Kjellin Zarah Schaal Tengyu Zhang Korbinian Löbmann Donglei Leng |
| author_facet | Xuezhi Zhuo Maud Margrethe Brekstad Kjellin Zarah Schaal Tengyu Zhang Korbinian Löbmann Donglei Leng |
| author_sort | Xuezhi Zhuo |
| collection | DOAJ |
| description | 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<sup>®</sup> 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% (<i>w</i>/<i>w</i>) 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. |
| first_indexed | 2024-03-09T11:27:25Z |
| format | Article |
| id | doaj.art-468e59b7884941d0b6e951dacb38b72d |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:27:25Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-468e59b7884941d0b6e951dacb38b72d2023-11-30T23:58:03ZengMDPI AGPharmaceutics1999-49232022-12-0115112610.3390/pharmaceutics15010126A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with RifaximinXuezhi Zhuo0Maud Margrethe Brekstad Kjellin1Zarah Schaal2Tengyu Zhang3Korbinian Löbmann4Donglei Leng5Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, DenmarkDepartment of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, DenmarkDepartment of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, DenmarkDepartment of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, DenmarkDepartment of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, DenmarkZerion Pharma A/S, Blokken 11, DK-3460 Birkerød, DenmarkAmorphous 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<sup>®</sup> 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% (<i>w</i>/<i>w</i>) 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.https://www.mdpi.com/1999-4923/15/1/126amorphous solid dispersionβ-lactoglobulinpolymerdissolutionnanocrystal |
| spellingShingle | Xuezhi Zhuo Maud Margrethe Brekstad Kjellin Zarah Schaal Tengyu Zhang Korbinian Löbmann Donglei Leng A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin Pharmaceutics amorphous solid dispersion β-lactoglobulin polymer dissolution nanocrystal |
| title | A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin |
| title_full | A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin |
| title_fullStr | A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin |
| title_full_unstemmed | A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin |
| title_short | A Comparative Study between A Protein Based Amorphous Formulation and Other Dissolution Rate Enhancing Approaches: A Case Study with Rifaximin |
| title_sort | comparative study between a protein based amorphous formulation and other dissolution rate enhancing approaches a case study with rifaximin |
| topic | amorphous solid dispersion β-lactoglobulin polymer dissolution nanocrystal |
| url | https://www.mdpi.com/1999-4923/15/1/126 |
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