Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic properties

Abstract

Direct tabletting of pharmaceutical materials is desirable to reduce the cost of production (1). However, compressing a high-dosed drug directly requires good micromeritic properties, such as flowability, and good and reproducible compression behavior. Spherical crystallization technique transforms directly the fine particles produced in crystallization or in the reaction process into a spherical shape. Agglomerates exhibit improved secondary characteristics, like flowability and compressibility, so that direct tabletting or coating is possible without further processing (mixing, agglomeration, sieving, etc.) (2, 3). Celecoxib, a non-steroidal anti-inflammatory drug (NSAID), is the first selective cyclooxygenase-2 inhibitor used in the treatment of osteoarthritis and rheumatoid arthritis in adult patients (4). Celecoxib exhibits poor flow and compression charac- Celecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP) using acetone, water and chloroform as solvent, non-solvent and bridging liquid, respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning electron microscopy (SEM). The IR spectroscopy and DSC results indicated the absence of any interactions between drug and additives. XRD studies showed a decrease in crystallinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The loading efficiency (% or mg drug per 100 mg crystals) was in the range of 93.9 ± 2.3 and 97.3 ± 1.3% (n = 3) with all formulations. The aqueous solubility and dissolution rate of the drug from crystals was significantly (p < 0.05) increased (nearly two times). The solubility and in vitro drug release rates increased with an increase in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal posseses a good spherical shape with smooth and regular surface.

Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer

“…The sink conditions was maintained by adding 0.25% (w/v) SDS in 1000 ml distilled water. 8,9 Each vessel was introduced the amount of sample equivalent to 40 mg celecoxib. At pre-determined time intervals, samples were withdrawn from the vessels through a 5 µm membrane filter (Millipore) followed by their spectrophotometric analysis employing a UV detector (UV-160A, Shimadzu, Japan) at 253 nm.…”

Recrystallization of Drugs: Significance on Pharmaceutical Processing

“…Moreover, the aqueous solubility and dissolution rate of the drug from crystals was notably increased nearly two times, with an increase in PVP concentration. In general, this technique may be applicable for producing oral solid dosage forms of other drugs with improved dissolution rate and oral bioavailability (Gupta et al, 2007). Correspondingly, use of these systems has the potential to facilitate drug development by saving valuable time in selecting the optimal physical or chemical characteristics of a given compound.…”

A Design of Experiment Approach for Optimization and Characterization of Etodolac Ternary System Using Spray Drying

“…The higher solubility of ETO in the basic media of intestine might be due to the acidic nature of ETO (indole acetic acid derivative) with a p a [30,31]. SS of plain ETO and its physical mixtures in simulated gastric fluid (SGF) pH 1.2 and phosphate buffer system (PBS) pH 6.8 with different carriers in the different selected ratios are depicted in table 2.…”