Solubility and dissolution enhancement of HPMC ‑ based solid dispersions of carbamazepine by hot‑melt extrusion technique

Sharadchandra Dagadu Javeer, Purnima Dhanraj Amin

Abstract


The objective of this study was to investigate solid dispersions (SDs) of poorly water soluble drug carbamazepine (CBZ),
prepared using low viscosity grade hydroxypropyl methyl cellulose (HPMC) (Methocel® E3 LV and Methocel® E5 LV)
by hot‑melt extrusion (HME) technology. Saturation solubility and dissolution profile of CBZ was studied. Characterization
of hot‑melt extruded samples was done by Fourier transform infrared spectroscopy (FTIR), differential scanning
calorimetry (DSC), and X‑ray diffraction studies (XRD). The result of the study showed the conversion of crystalline form
of drug into amorphous form indicating increase in saturation solubility and dissolution rate of CBZ.
Key words: Carbamazepine, hot‑melt extrusion, hydroxypropyl methyl cellulose

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References


Naima Z, Siro T, Juan‑Manuel GD, Chantal C, René C, Jerome D.

Interactions between carbamazepine and polyethylene glycol (PEG)

: Characteristics of physical, solid dispersed and eutectic mixtures.

Eur J Pharm Sci 2001;12:395‑404.

Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to

improve oral bioavailability of poor water soluble drugs. Drug Discov

Today 2007;12:1068‑75.

Craig DQ. The mechanisms of drug release from solid dispersions in

water‑soluble polymers. Int J Pharm 2002;231:131‑44.

Serajuddin AT. Solid dispersion of poorly water‑soluble drugs: Early

promises, subsequent problems, and recent break‑throughs. J Pharm

Sci 1999;88:1058‑66.

Breitenbach J. Melt extrusion: From process to drug delivery technology.

Eur J Pharm Biopharm 2000;54:107‑17.

Leuner C, Dressman J. Improving drug solubility for oral delivery using

solid dispersions. Eur J Pharm Biopharm 2000;50:47‑60.

Klein CE, Chiu YL, Awni W, Zhu T, Heuser RS, Doan T, et al. The tablet

formulation of lopinavir/ritonavir provides similar bioavailability to the soft‑gelatin capsule formulation with less pharmacokinetic variability and

diminished food effect. J Acquir Immune Defic Syndr 2007;44:401‑10.

Miller DA, McConville JT, Yang W, Williams RO 3rd, McGinity JW.

Hot‑melt extrusion for enhanced delivery of drug particles. J Pharm

Sci 2007;96:361‑76.

Radl S, Tritthart T, Khinast JG. A novel design for hot‑melt extrusion

pelletizers. Chem Eng Sci 2010;65:1976‑88.

Hardung H, Djuric D, Ali S. Combining HME and solubilization:

Soluplus - the solid solution. Drug Deliv Technol 2010;10:20‑7.

Patterson JE, James MB, Forster AH, Rades T. Melt extrusion and spray

drying of carbamazepine and dipyridamole with polyvinylpyrrolidone/

vinyl acetate copolymers. Drug Dev Ind Pharm 2008;34:95‑106.

Rowe RC, Sheskey PJ, Quinn ME. Handbook of pharmaceutical

excipients, 6th ed. London: Pharmaceutical Press; 2009. p. 326‑9.

Higuchi T, Connors KA. Phase‑solubility techniques. Adv Anal Chem

Instrum 1965;4:117‑212.

United States Pharmacopeia National Formulary, USP30/NF 25.

Dissolution Carbamazepine tablets. Rockville MD: United States

Pharmacopeial Convention, Inc.; 2007. p. 1616.

Rosen MJ. Surfactants and interfacial phenomena. 3rd ed. New Jersy:

Wiley Interscience Publication; 2004. p. 1‑2.

Kipouros K, Kachrimanis K, Nikolakakis I, Tserki V, Malamataris S.

Simultaneous quantification of carbamazepine crystal forms in ternary

mixtures (I, III and IV) by diffuse reflectance spectroscopy (DRIFTS) and

multivariate calibration. J Pharm Sci 2006;95:2419‑31.

Grzesiak AL, Lang M, Kim K, Matzges AJ. Comparison of the four

anhydrous polymorphs of carbamazepine and the crystal structure of

form I. J Pharm Sci 2003;92:2260‑71.

Corrigan OI, Holohan EM. Amorphous spray‑dried hydroflumethia

zide-polyvinylpyrrolidone systems: Physicochemical properties. J Pharm

Pharmacol 1984;36:217‑21.




DOI: http://dx.doi.org/10.22377/ajp.v8i2.348

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