Zerion Pharma A/S, Fruebjergvej 3, 2100, Copenhagen, Denmark.
Science for Novartis Pharma AG, Lichtstrasse 35, Ch-4002, Basel, Switzerland.
Pharm Res. 2023 Jul;40(7):1865-1872. doi: 10.1007/s11095-023-03542-9. Epub 2023 May 26.
Whey protein isolate (WPI) has previously been shown to be a promising new excipient for the development of amorphous solid dispersions (ASD) at a high drug loading of 50% (w/w). Whilst WPI is a protein mixture, comprising mainly the three proteins β-lactoglobulin (BLG), α-lactalbumin (ALA), casein glycomacropeptides (CGMP), the individual contributions of these three proteins to the overall performance of whey protein based ASDs has still not been investigated. In addition, the limitations of the technology at even higher drug loadings (i.e., more than 50%) have not yet been explored. In this study, BLG, ALA, CGMP and WPI were each prepared as ASDs with the two poorly water-soluble drugs (Compound A and Compound B) at 50%, 60% and 70% drug loadings.
Solid state characterization, dissolution rate and physical stability of the obtained samples were analyzed.
All the obtained samples were amorphous and showed faster dissolution rates compared to the respective pure crystalline drugs. However, the BLG based formulations-at least for Compound A-were outperforming the other ASDs in terms of stability, dissolution enhancement and solubility increase.
Overall, the study confirmed that the investigated whey proteins showed their potential in developing ASDs even at high drug loadings of up to 70%.
乳清蛋白分离物（WPI）已被证明是一种很有前途的新型赋形剂，可用于开发高载药量为 50%（w/w）的无定形固体分散体（ASD）。虽然 WPI 是一种蛋白质混合物，主要由三种蛋白质β-乳球蛋白（BLG）、α-乳白蛋白（ALA）和酪蛋白糖巨肽（CGMP）组成，但这三种蛋白质对乳清蛋白基 ASD 整体性能的各自贡献仍未得到研究。此外，该技术在更高载药量（即 50%以上）下的局限性尚未得到探索。在这项研究中，BLG、ALA、CGMP 和 WPI 分别与两种水溶性较差的药物（化合物 A 和化合物 B）以 50%、60%和 70%的载药量制备成 ASD。
对所得样品的固态特性、溶出速率和物理稳定性进行了分析。
所有得到的样品均为无定形，与各自的纯晶型药物相比，溶出速率更快。然而，BLG 基制剂——至少对于化合物 A——在稳定性、溶出增强和溶解度提高方面优于其他 ASD。
总的来说，该研究证实，即使在高达 70%的高载药量下，所研究的乳清蛋白在开发 ASD 方面也显示出了潜力。
