Designing starch-based fenofibrate formulations using the melting method

Fenofibrate (FNF) is used to treat hyperlipidemia. However, FNF is a poorly water-soluble drug, and the dosage of commercial products is relatively high at 160 mg in a Lipidil® tablet. Therefore, this study aimed to develop an FNF-solid dispersion (SD) that solubilizes and stabilizes FNF. The melting method that uses the low melting point of FNF was employed. The dissolution percentage of FNF in the optimal formulation (SD2) increased by 1.2-, 1.3-, and 1.3-fold at 5 min compared to that of Lipidil® and increased by 2.0-, 2.1-, and 2.0-fold compared to the pure FNF in pH 1.2 media, distilled water, and pH 6.8 buffer, which included 0.025 M sodium lauryl sulfate, respectively.

Highlights

Fenofibrate (FNF) SD formulation with Starch#1500 and TPGS was prepared using a melting method.

The dissolution (%) of FNF in SD2 formulation is improved compared to those of Lipidil® and the other formulations.

The SD2 formulation is well maintained the stability (drug content and pre-dissolution [%]) for 6 months.

The SD2 formulation showed a dissolution percentage of nearly 100 % in all dissolution media after 60 min. The physicochemical properties of the SD2 formulation exhibited slight changes in the melting point and crystallinity of FNF. Moreover, the stability of the SD2 formulation was maintained for six months. In particular, it was challenging to secure stability when starch#1500 was excluded from the SD2 formulation. In conclusion, the dissolution percentage of FNF in the SD2 formulation was improved owing to the weak binding force between FNF and the excipients, stability was secured, and favorable results are expected in future animal experiments.

Materials

FNF was obtained from the Physical Pharmacy Laboratory (Chungnam National University). Aerosil® (200 and 300) were obtained from Evonik (Essen, Germany). Lactose (Flowlac®100) was purchased from DFE Pharma (Goch, Germany). Microcrystalline cellulose (MCC, Avicel®PH-102), Pearlitol® 160 C (mannitol), starch#1500, granular dicalcium phosphate anhydrate, and granular dicalcium phosphate dihydrate were obtained from Whawon Pharm (Seoul, Korea). Neusilin® (US2 and UFL2) was obtained from Fuji Chemical.

Jeong Sun Sohn, Ye Eun Choi, Jin-Seok Choi, Designing starch-based fenofibrate formulations using the melting method, International Journal of Biological Macromolecules, 2024, 132903, ISSN 0141-8130, https://doi.org/10.1016/j.ijbiomac.2024.132903.