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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Apremilast (APST) is an oral phosphodiesterase 4 (PDE4) inhibitor for active psoriatic arthritis.
• Low solubility of APST limits its dissolution and oral bioavailability.
• Novel drug delivery systems are needed to overcome APST's solubility challenges.

Purpose of the Study:

• To develop and characterize an APST solid dispersion to improve its dissolution and oral bioavailability.
• To investigate the impact of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) on APST properties.
• To evaluate the in vitro and in vivo performance of the developed solid dispersion.

Main Methods:

• Spray drying was employed to create APST solid dispersions with TPGS and PVPVA.
• TPGS variants were synthesized to optimize solubilizing capacity.
• Solid state characterization used X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR).
• In vitro dissolution studies were conducted in phosphate buffered saline (pH 6.8).
• In vivo pharmacokinetic studies were performed in rats.

Main Results:

• The solid dispersion successfully rendered APST amorphous.
• In vitro dissolution showed a remarkable increase, with 90% release within 10 minutes.
• In vivo studies demonstrated significant improvements in APST bioavailability, with Cmax and AUClast increasing 22- and 12.9-fold, respectively, compared to APST form B.

Conclusions:

• APST solid dispersion with TPGS and PVPVA is an effective strategy to enhance drug solubility.
• This formulation represents a promising alternative drug delivery system for improving APST oral bioavailability.
• The developed solid dispersion offers a viable approach for treating psoriatic arthritis with improved therapeutic outcomes.