Abstract
The aim of the present study was to improve the solubility of poorly water soluble drug lovastatin (LS) by solid dispersion (SD) techniques using modified locust bean gum (MLBG) as a carrier. The locust bean gum (LBG) was modified by heating and there observed irreversible decrease in viscosity, whereas swelling property remains unaffected. The advantage of modification of LBG was illustrated by difference in dissolution profiles of their SD. Effect of polymer concentration and methods of preparation on solubility enhancement were studied using solubility and dissolution studies, respectively. The result of solubility study showed increase in solubility of LS with increase in concentration of MLBG. It was found that the dissolution rate of LS from its SD was dependent on the method of preparation of solid dispersions. Dissolution study revealed that the modified solvent evaporation is most convenient and effective method for solubility enhancement of poorly water soluble drug LS, among various methods of preparation of SD. The prepared SDs were characterized by differential scanning calorimetry, scanning electron microscopy, and X-ray diffraction study. In vivo study was performed by measuring 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG Co-A) reductase inhibition activity. Significant reduction in HMG Co-A reductase activity was observed in case of solid dispersions of LS than plain LS. In conclusion, MLBG could be used as a potential carrier in enhancing the dissolution rate and bioavailability of LS.
Similar content being viewed by others
References
G. V. Murali Mohan Babu, Ch. D. S. Prasad, and K. V. Raman Murthy. Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water soluble drug nimodipine. Int. J. Pharm. 234:1–17 (2002).
S. Roller, and S. A. Jones. Handbook of fat replacers, CRS, Boca Raton, FL, 1996.
F. Ohwavworhu, and T. Adelakun. Phosphoric acid-mediated depolymerization and decrystallization of α-cellulose obtained from Corn Cob: Preparation of low crystallinity cellulose and some physicochemical properties. Trop. J. Pharm. Res. 4:509–516 (2004).
K. Reddy, S. Mutalik, and S. Reddy. Once daily sustained release matrix tablets of nicorandil: Formulation and in vitro evaluation. AAPS PharmSciTech. 4:E61–E66 (2003).
A. Modi, and P. Tayade. Enhancement of dissolution profile by solid dispersion (kneading) technique. AAPS PharmSciTech. 7:E1–E6 (2006).
A. Paradkar, A. A. Ambike, and B. K. Jadhav. Characterization of curcumin—PVP solid dispersion obtained by spray drying. Int. J. Pharm. 271:281–286 (2004).
B. Chauhan, S. Shimpi, and A. Paradkar. Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying techniques. Eur. J. Pharm. Sci. 26:219–230 (2004).
E. J. Kim, M. K. Chun, J. S. Jang, I. H. Lee, K. R. Lee, and H. K. Choi. Preparation of a solid dispersion of felodipine using a solvent wetting method. Eur. J. Pharm. Biopharm. 64:200–205 (2006).
Y. Rane, R. Mashru, M. Sankalia, and J. Sankalia. Effect of hydrophilic swellable polymers on dissolution enhancement of carbamazepine solid dispersions studied using response surface methodology. AAPS PharmSciTech. 8:E1–E11 (2007).
A. Venugopala Rao, and S. Ramkrishnan. Indirect assessment of hydroxymethyl glutaryl CoA reductase (NADPH) activity in liver tissue. Clin. Chem. 21:1523–1525 (1975).
Y. Chao, J. S. Chen, V. M. Hunt, G. W. Kuron, J. D. Karkas, R. Liou, and A. W. Alberts. Lowering of plasma cholesterol levels in animals by lovastatin and simvastatin. Eur. J. Clin. Pharmacol. 40(Suppl 1):S 11–S 14 (1991).
A. Portero, C. Rermunan-Lopez, and J. L. Vila-Jato. Effect of chitosan and glutamate enhancing the dissolution properties of poorly water soluble drug nifedipine. Int. J. Pharm. 175:75–84 (1998).
Acknowledgment
Authors are thankful to Biocon, Banglore, India and Taiyo Lucid Pvt. Ltd., Mumbai, India for providing gift sample of lovastatin and locust bean gum, respectively.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Patel, M., Tekade, A., Gattani, S. et al. Solubility Enhancement of Lovastatin by Modified Locust Bean Gum Using Solid Dispersion Techniques. AAPS PharmSciTech 9, 1262–1269 (2008). https://doi.org/10.1208/s12249-008-9171-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-008-9171-4