Solid Dispersions of Cefixime Using β-Cyclodextrin: Characterization and in vitro Evaluation

Authors: Nagasamy Venkatesh Dhandapani, Amged Awad El-Gied

Abstract:

Cefixime, a BCS class II drug, is insoluble in water but freely soluble in acetone and in alcohol. The aqueous solubility of cefixime in water is poor and exhibits exceptionally slow and intrinsic dissolution rate. In the present study, cefixime and β-Cyclodextrin (β-CD) solid dispersions were prepared with a view to study the effect and influence of β-CD on the solubility and dissolution rate of this poorly aqueous soluble drug. Phase solubility profile revealed that the solubility of cefixime was increased in the presence of β-CD and was classified as A_L-type. Effect of variable, such as drug:carrier ratio, was studied. Physical characterization of the solid dispersion was characterized by Fourier transform infrared spectroscopy (FT-IR) and Differential scanning calorimetry (DSC). These studies revealed that a distinct loss of drug crystallinity in the solid molecular dispersions is ostensibly accounting for enhancement of dissolution rate in distilled water. The drug release from the prepared solid dispersion exhibited a first order kinetics. Solid dispersions of cefixime showed a 6.77 times fold increase in dissolution rate over the pure drug.

Keywords: Cefixime, β-Cyclodextrin, solid dispersions, kneading method, dissolution, release kinetics.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1339912

References:

[1] Amidon GL, Lennernas H., Shah VP, Crison, JR. Pharm Res, 1995; 12: 413-420.
[2] Leuner C, Dressman J. Eur J Pharm Biopharm. 2000; 50: 47-60.
[3] Lipinski C. Am. Pharm. Rev. 2002; 5: 82-85.
[4] Hu J, Johnson KP, Williams, RO. Int J Pharm. 2004; 271: 145-154.
[5] Madhusudhan B, Rambhav D, Gudsoorkar VR, Shete JS, Apte SS. Studies on sulphamethoxazole solid dispersions and their tablets. Indian J. Pharm. Sci, 2002; 64(3): 233-238.
[6] Delahaye N, Duclos R, Saiter JM, Varnier S. Characterization of solid dispersions phase transitions using a new optical thermal analyzer. Drug Dev. Ind. Pharm., 1997; 23(3): 293-303.
[7] Okimoto K, Miyake M, Ibuki R, Yasumura M, Ohnishi N, Nakai T. Dissolution mechanism and rate of solid dispersion particles of nilvadipine with hydroxyl propyl methyl cellulose. Int. J. Pharm, 1997; 159: 85-93.
[8] Yamada T, Saito N, Imai T, Otagiri M. Effect of grinding with hydroxyl propyl cellulose on the dissolution and particle size of a poorly water soluble drug. Chem. Pharm. Bull, 1999;47(9): 1311-1313.
[9] Narang A, Srivastava A. Evaluation of solid dispersions of clofazimine. Drug Dev. Ind. Pharm, 1990;28: 875-882.
[10] Chiou WL and Riegelman S. Pharmaceutical applications of solid dispersion system. J. Pharm. Sci, 1971; 60: 1281-1302.
[11] Chiou WL and Riegelman S. Preparation and dissolution characterization of several fast release solid dispersions of griseofulvin. J. Pharm. Sci, 1969; 58: 1505-1510.
[12] Millic AJ, Rajic DS, Tasic LJ, Djuric S, Kasa P, Pintye HK. Etodolac and solid dispersion with β-cyclodextrin. Drug Dev. Ind. Pharm, 1997; 23(11): 1123-1129.
[13] Moyano JR, Arias MJ, Gines JM, Perez JI, Rabasco AM. Dissolution behavior of oxazepam in presence of cyclodextrins, Evaluation of oxazepam – dimers binary system. Drug Dev. Ind. Pharm, 1997; 23(4): 379-385.
[14] Prasanna SRV, Sunil Babu Koppula. International Journal Of Biopharma Research, 2013; 2 (3): 104-110
[15] Aftab Modi, Pralhad Tayade. AAPS PharmScitech, 2006; 7(3): Article 6.