Abstract
The purpose of the present investigation was to increase the solubility and dissolution rate of celecoxib (CLX) by preparing microcrystals of drug by solvent change precipitation. This procedure was optimized in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. CLX agglomerates were prepared with brij35 (stabilizer agent) using acetone as solvent, water as non-solvent, respectively. The agglomerates were characterized by DSC, XRD, FTIR studies. A full-factorial design was employed to study the effect of independent variables, the amounts of stirring rate (X1), volume of organic solvent (X2), volume of aqueous solvent (X3), time of stirring (X4), concentration of Brij (X5), concentration of Tween 80 (X6), concentration of HPMC (X7) on dependent variables, particle size (PS), drug content (DC), drug released after 15 min (Q15), crystal yield (CY), Gibbs free energy change (ΔG°tr), antalpy change (ΔH) and saturated solubility (Ss). The DSC and FTIR results indicated the absence of any interactions between drug and stabilizers. These studies showed a decrease in crystalinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The drug content and crystal yield were in the range of 32.84-48.22% and 64.55-83.33% with all formulations, respectively. The solubility and drug release rates increased with an increase in concentration of stabilizer. The results show that microcrystals of the drug in stabilizer considerably enhanced the dissolution rate.
Highlights
Micronization is the common method to increase specific surface area
A fullfactorial design was employed to study the effect of independent variables, the amounts of stirring rate (X1), volume of organic solvent (X2), volume of aqueous solvent (X3), time of stirring (X4), concentration of Brij (X5), concentration of Tween 80 (X6), concentration of Hydrxypropylmethyl Cellulose (HPMC) (X7) on dependent variables, particle size (PS), drug content (DC), drug released after 15 min (Q15), crystal yield (CY), Gibbs free energy change (ΔG°tr), antalpy change (ΔH) and saturated solubility (Ss)
The results show that microcrystals of the drug in stabilizer considerably enhanced the dissolution rate
Summary
Micronization is the common method to increase specific surface area. Various types of mechanical mills are used to reduce the large crystals into smaller. Micronization means transfer of the coarse drug powder to an ultrafine powder with a mean particle size being typically in the range of 2-5 μm, size distributions normally ranges from approximately 0.1 to 25 μm. Very recently micronization doesn’t lead to a very effective increment in the bioavailability.[1] The bioavailability intrinsically related to drug particle size. By reducing particle size, increased surface area improves the dissolution properties. In this method, typically, low excipient to drug ratios is required. Formulations are generally well tolerated provided that strong surfactants are not required for stabilization
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