Comparative Evaluation of Solubility and Dissolution Enhancement of Bicalutamide Solid by Dispersion Technique

Bicalutamide is poorly water soluble Anti- Cancer drug used in prostate cancer. Due to poor solubility of drug, its bioavailability rate is limited by drug dissolution. In the present study, an attempt has been made to increase solubility and dissolution of Bicalutamide by solid dispersion technique using Solvent Evaporation and Hot Melt method with PEG- 6000 (Poly ethylene glycol), PVP K-90 (Poly vinyl pyrrolidone), and Poloxamer F-68.

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Effects of various parameters such as type of carrier system used, drug: carrier ratio were studied. The evaluation of solid dispersion was done by IR spectroscopy, solubility and dissolution studies. Improvement in dissolution of drug was observed in all solid dispersions as compared to pure drug. The dissolution rate of Bicalutamide was directly proportional to increment in proportion of the carrier  Pure Bicalutamide showed only 48% drug release in 1 hour whereas the Solid dispersion prepared by Solvent Evaporation method, using PEG 6000 showed faster in vitro drug release.

Poorly water soluble compounds have solubility and dissolution related bioavailability problems. The dissolution rate is directly proportional to solubility of drug. Drugs with low aqueous solubility have low dissolution rates and hence suffer from poor oral bioavailability. The solid dispersion approach has been widely used to improve the solubility, dissolution rate, and consequently the bioavailability of poorly water soluble drugs. Solid dispersion is defined as dispersion of one or more active ingredients in an inert carrier or matrix at solid state prepared by melting, solvent, or melting solvent method. The release mechanism of drug from variety of solid dispersions depends upon the physical properties of carriers as well as drug substance and preparation method. 

There are number of carriers used in the preparation of solid dispersion like acids, sugars, polymeric materials, surfactants4. Bicalutamide N-[4-cyano-3-(trifluoromethyl) phenyl]-3-[(4-fluorophenyl) sulfonyl]-2-hydroxy-2- methylpropanamide) 5 is an oral non steroidal anti-androgen used in the treatment of prostate cancer and hirsutism. It was first launched in the 1995 as combination treatment for advanced prostate cancer and subsequently launched as monotherapy for the treatment of earlier stages of diseases6. The present investigation was an attempt to improve the dissolution rate of Bicalutamide by solid dispersion using PEG- 6000, PVP K-90, and Poloxamer F-68 as carriers. Solid dispersion of Bicalutamide was prepared by Solvent Evaporation and Hot Melt method using three different proportions of drug: carrier. All the solid dispersions were characterized for IR spectroscopy, solubility study and dissolution study.

The whole 6 pages article is available for download here.