Preparation of microcrystals of piroxicam monohydrate by antisolvent precipitation via microfabricated metallic membranes with ordered pore arrays

Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallisation via metallic membranes with ordered pore arrays. Crystallisation was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7–34 μm and was controlled by the PRX concentration in the feed solution (15 −25 g L−1), antisolvent/solvent volume ratio (5–30), and the type of antisolvent (Milli-Q water or 0.1−0.5 wt% aqueous solutions of hydroxypropyl methyl2 cellulose (HPMC), polyvinyl alcohol or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L−1 PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt% HPMC solution stirred at 1,500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilisation of microcrystals against agglomeration than polyvinyl alcohol and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystalliser. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals.