Acta Pharm. 57 (2007) 287-300

10.2478/v10007-007-0023-7

full paper

Original research paper

Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizers

RAVINDRA S. DHUMAL, SHAMKANT L. SHIMPI and ANANT R. PARADKAR*

arparadkar@rediffmail.com

Department of Pharmaceutics, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy and Research Centre, Erandawane, Pune-411 038, Maharashtra, India

Accepted June 11, 2007

The purpose of this study was to obtain an amorphous system with minimum unit operations that will prevent recrystallization of amorphous drugs since preparation, during processing (compression) and further storage. Amorphous celecoxib, solid dispersion (SD) of celecoxib with polyvinyl pyrrollidone (PVP) and co-precipitate with PVP and carrageenean (CAR) in different ratios were prepared by the spray drying technique and compressed into tablets. Saturation solubility and dissolution studies were performed to differentiate performance after processing. Differential scanning calorimetry and X-ray powder diffraction revealed amorphous form of celecoxib, whereas infrared spectroscopy revealed hydrogen bonding between celecoxib and PVP. The dissolution profile of the solid dispersion and co-precipitate improved compared to celecoxib and amorphous celecoxib. Amorphous celecoxib was not stable on storage whereas the solid dispersion and co-precipitate powders were stable for 3 months. Tablets of the solid dispersion of celecoxib with PVP and physical mixture with PVP and carrageenean showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenean showed no evidence of crystallinity during stability studies with comparable dissolution profiles. This extraordinary stability of spray-dried co-precipitate tablets may be attributed to the cushioning action provided by the viscoelastic polymer CAR and hydrogen bonding interaction between celecoxib and PVP. The present study demonstrates the synergistic effect of combining two types of stabilizers, PVP and CAR, on the stability of amorphous drug during compression and storage as compared to their effect when used alone.

Keywords: celecoxib, amorphous, solid dispersion, co-precipitate, PVP, carrageenean, compression, stability, tableting