Department of Inorganic & Analytical Chemistry, Collegium Pharmaceuticum, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland; Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, Odense 5230, Denmark.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, Odense 5230, Denmark.
Int J Pharm. 2023 Sep 25;644:123294. doi: 10.1016/j.ijpharm.2023.123294. Epub 2023 Aug 6.
Amorphous solid dispersions (ASD) represent a viable formulation strategy to improve dissolution and bioavailability of poorly soluble drugs. Our study aimed to evaluate the feasibility and potential role of hydrogenated phospholipid (HPL) as a matrix material and solubilizing additive for binary (alone) or ternary (in combination with polymers) solid dispersions, using fenofibrate (FEN) as the model drug. FEN, incorporated within ASDs by melting or freeze-drying (up to 20% m/m), stayed amorphous during short-term stability studies. The solubility enhancing potential of HPL depended on the dissolution medium. In terms of enhancing in vitro permeation, solid dispersions with HPL were found equally or slightly more potent as compared to the polymer-based ASD. For studied ASD, in vitro permeation was found substantially enhanced as compared to a suspension of crystalline FEN and at least equal compared to marketed formulations under comparable conditions (literature data). Additionally, while the permeation of neat FEN and FEN in binary solid dispersions was affected by the dissolution medium (i.e., the "prandial state"), for ternary solid dispersions the permeation was independent of the "prandial state" (FaSSIF = FeSSIF). This suggests that ternary solid dispersions containing both polymer and HPL may represent a viable formulation strategy to mitigate fenofibrate's food effect.
无定形固体分散体（ASD）是一种提高难溶性药物溶解和生物利用度的可行制剂策略。本研究旨在评估氢化磷脂（HPL）作为基质材料和增溶剂的可行性和潜在作用，用于二元（单独）或三元（与聚合物结合）固体分散体，以非诺贝特（FEN）为模型药物。通过熔融或冷冻干燥（高达 20%m/m）将 FEN 掺入 ASDs 中，在短期稳定性研究中保持无定形状态。HPL 的增溶潜力取决于溶解介质。就体外渗透增强而言，与基于聚合物的 ASD 相比，含有 HPL 的固体分散体具有同等或稍强的作用。对于研究的 ASD，与结晶 FEN 的混悬液相比，体外渗透有了显著增强，并且在可比条件下至少与市售制剂相当（文献数据）。此外，虽然纯 FEN 和二元固体分散体中 FEN 的渗透受到溶解介质的影响（即“进食状态”），但对于三元固体分散体，渗透不受“进食状态”的影响（FaSSIF=FeSSIF）。这表明含有聚合物和 HPL 的三元固体分散体可能是减轻非诺贝特食物效应的一种可行制剂策略。
