Alternate solid form synthesis, characterization and stability of phosphodiesterase 4 inhibitor

Abstract

Abstract Apremialst is a phosphodiesterase 4 (PDE 4) inhibitor. It is used for the treatment of psoriatic arthritis. It is a low soluble and low permeable BCS class IV drug. In the current study, Apremilast alternate solid form (amorphous) is synthesized to address the low solubility issue. The synthesis consists of antisolvent precipitation technique using n-heptane as an antisolvent and acetone as a solvent. The obtained amorphous form has successfully scaled up to 100 g using same method. The synthesized amorphous form is characterized using PXRD, DSC, TGA, Dynamic Vapour Sorption analyser (DVS) and HPLC technique. X-ray halo pattern along with MDSC glass transition temperature of 77.63 °C (I) are the evidence for the amorphous nature of the Apremilast solid form and stability of the amorphous form. Dynamic water vapour sorption analysis is revealed the ease of handling property of the amorphous solid form with slightly hygroscopic nature. Amorphous form had shown multi fold solubility advantages over the Apremialst counterpart marketed crystalline Form-B in water and biological compartment related USP buffers. Intrinsic dissolution rate of amorphous form also has the same advantage. The prepared amorphous form is robust to pharmaceutical process operations like milling, compaction, drying and high humidity. Appremilast amorphous form is stable for 6 months at 40 °C and 75% RH for 6 months. In the light of current studies, amorphous form of the Apremilast may be taken up for the drug product development.