Development of Apremilast Solid Dispersion Using TPGS and PVPVA with Enhanced Solubility and Bioavailability

• Published in: AAPS PharmSciTech 2021-04, Vol.22 (4), p.142, Article 142
• Main Authors: Yang, Liuhong, Wu, Penghui, Xu, Jinchao, Xie, Dihuan, Wang, Zhongqing, Wang, Qian, Chen, Yong, Li, Chuan Hua, Zhang, Jiaxin, Chen, Hangping, Quan, Guilan
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calorimetry, Differential Scanning; Dosage Forms; Pharmacology/Toxicology; Pharmacy; Phosphodiesterase 4 Inhibitors - chemistry; Phosphodiesterase 4 Inhibitors - pharmacokinetics; Povidone - analogs & derivatives; Povidone - chemistry; Powder Diffraction; Rats; Research Article; Solubility; Spectroscopy, Fourier Transform Infrared; Thalidomide - analogs & derivatives; Thalidomide - chemistry; Thalidomide - pharmacokinetics; Vitamin E - chemistry
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-021-02005-x

Apremilast (APST) is an effective inhibitor of phosphodieasterase 4 (PDE4) which is the first oral drug for the treatment of adult patients with active psoriatic arthritis. However, Apremilast ’ s low solubility restricts its dissolution and bioavailability. In this study, APST solid dispersion with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) was developed to improve the dissolution and bioavailability of APST by spray drying. A series of TPGS were synthesized to elucidate the effect of the ratio of monoester to diester on solubilizing capacity. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were used to characterize the solid dispersion, and the results showed that APST was amorphous in solid dispersion. In vitro dissolution study showed that the dissolution rate of solid dispersion in phosphate buffered saline (pH 6.8) was remarkably increased, reaching a release of 90% within 10 min. Moreover, in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, its C max and AUC last were nearly 22- and 12.9-fold greater as compared to APST form B, respectively. In conclusion, APST solid dispersion with TPGS and PVPVA is an alternative drug delivery system to improve the solubility and oral bioavailability of APST.