Modification of the crystal habit of celecoxib for improved processability

Abstract

Crystallization is often used in the pharmaceutical industry for purification and isolation of drugs, and also as a means of generating polymorphs or isomorphs. The aim of this study was to investigate the role of extrinsic crystallization parameters on the crystallized product, with special emphasis on improving the mechanical properties of acicular celecoxib. Celecoxib isomorphs were prepared using different techniques (solvent crystallization and vapour diffusion) and crystallization conditions (solvents, stirring, degree of supersaturation, crystallization temperature and seeding). Powder X-ray diffractometry, spectroscopic and thermal methods were used to investigate physical characteristics of crystals. Growth kinetics and aggregation dynamics of crystallization in polar and non-polar solvents were simulated using a dynamic light scattering method. The quick appearance of broad peaks over the range of 10-8000 nm in chloroform during crystallization simulation studies indicated faster aggregation in non-polar solvents. Aspect ratio, flow, compressibility and surface area of recrystallized products were also determined. Surface topography was determined by atomic force microscopy and the lath-shaped crystals (aspect ratio of 2-4) exhibited a roughness index of 1.79 in comparison with 2.92 for needles. Overall, the lath-shaped isomorphs exhibited improved flow and better compressibility.

Role of excipients in the crystallization of Albendazole

“…The aspect ratio (AR) for control batch and treated crystals was found to be 3.12 ± 1.62, 1.90 ± 0.72 (2:1) and 2.16 ± 0.34 (3:1), respectively. This modified habit of treated crystals with least AR imparted better flow property compared with pure ABZ and control batch [29]. Flow property of pure drug was poor (Table 2) because of small and irregular shaped particles with a strong tendency to aggregate because of electrostatic charge generated on their surface [20,21].…”

“…Treated crystals showed even more improved flow characteristics compared with pure drug as well as control batch crystals. Equidimensional shape of treated crystals was responsible for its good flow property compared with pure ABZ [29]. However, small agglomerated pure ABZ crystals were responsible for its poor flow and stickiness because of electrostatic charge generation on its surface.…”

“…Sample was put on the slide (minimum of 300 particles) and particle size was determined by measuring longest dimension of each particle. Mean aspect ratio (AR) which is defined as the ratio of length (longest dimension from edge to edge of a particle oriented parallel to the ocular scale) to the width (the longest dimension of the particle measured at right angles of the length) of the particle, was determined [29]. The size of 300 randomly selected particles from prepared batch was measured.…”

Recrystallization of Drugs: Significance on Pharmaceutical Processing

“…Variety of papers in this case is representative of the suitability of this drug for spherical crystallization process to enhance the flow, compressibility and solubility properties of seems to be a beneficial objective to improve the following therapeutic efficacy of celecoxib (Banga et al, 2007). Paradkar et al improved the micromeritic and compressional properties of celecoxib by a spherical crystallization process using the solvent change method.…”

Physicochemical Characterization of Pharmaceutical Solids

“…An evaluation of various habits of celecoxib showed that the lath-shaped crystals had better flow and compressibility characteristics (Banga et al, 2007). Swaminathan and Kildsig (2000) demonstrated that the surface roughness of particle carriers had a significant effect on the stability of powder mixtures.…”