Selection of amorphous solid dispersion matrix/carriers for Luteolin

Abstract

Luteolin (LUT), a bioflavonoid found in many plants, shows significant formulation problems due to its poor aqueous solubility and water stability [1]. One way to overcome these limitations is to formulate the drug in suitable amorphous solid dispersions (ASDs) [2]. However, the selection of a proper ASD matrix/carrier is a nontrivial task. Therefore, the aim of the present study is to evaluate several polymeric matrix/carriers and select the most promising for the preparation of a stable LUT ASD system. Initially, the glass forming ability of LUT was evaluated using a DSC-based method [3]. Results showed that the API is a good glass former since no thermal events were observed during drugʼs quench-cooling and reheating. Then, six commonly used polymeric ASD matrix/carriers (namely povidone, PVP, coPovidone, coPVP, hydroxypropyl cellulose, HPC-SL, hydroxypropyl methyl cellulose acetate succinate, HPMC-AS, Eudragit® RS, Eud-RS, and Soluplus®, SOL) were tested as to whether they can inhibit successfully LUTʼs recrystallization. In this vein, binary ASDs were prepared using the film-casting method. Then, the ASD casts were placed in accelerating storage conditions (40 ± 2 oC/75 ± 5% RH) and the formation of LUT crystals was evaluated via polarized light microscopy. In the case of the pure API, and ASDs using Eud-RS, HPC-SL, HPMC-AS and SOL, high drugʼs recrystallization was recorded starting from day one. On the contrary, binary LUT ASDs using PVP and coPVP showed good amorphous stability, up to 21 days of storage, attributed to API-polymer strong intermolecular interactions (revealed via ATR-FTIR spectroscopy).