PREPARATION AND CHARACTERIZATION OF SOLID DISPERSION FAMOTIDINE â€“ MANNITOL BY CO-GRINDING METHOD
Objective: This study aims to prepare and characterize solid dispersion of famotidine using mannitol to enhance the solubility and dissolution rate.
Methods: Solid dispersions were prepared by co-grinding method in 9 formulas. The ratio of famotidine and mannitol was varied (1:1, 1:2, 2:1 w/w),
and each ratio was milled at three different times (30, 60, and 90 minutes). The physical mixture was also prepared as comparison at ratio 1:1 w/w.
Solid dispersions were characterized by X-ray diffraction analysis, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry
(DSC) analysis, scanning electron microscopy (SEM), particle size analysis, solubility, and dissolution rate study. The assay of famotidine was done
using a UV spectrophotometer.
Results: The highest solubility of famotidine in solid dispersion was obtained in F2 (ratio 1:2 and grinding time 30 minutes). The solubility of intact
famotidine, physical mixture, and solid dispersion F2 was 1.630Â±0.027, 2.757Â±0.096, and 3.272Â±0.076 mg/ml, respectively. X-ray diffractogram of
solid dispersion F2 showed a decrease in the peak intensity of famotidine. Thermogram of DSC showed a decrease of famotidine melting point for both
physical mixture and solid dispersion. Photomicrograph of SEM indicated the changes in morphology solid dispersion compared to intact substances.
FTIR analysis showed no chemical interaction between famotidine and mannitol. The particle size analysis showed a reduction in the particle size
of the solid dispersion. The dissolution result after 60 minutes was 85.029%, 86.166%, 92.057% for intact famotidine, physical mixture, and solid
dispersion F2, respectively.
Conclusion: Solid dispersion increased solubility and dissolution rate.
Keywords: Solid dispersion, Famotidine, Mannitol, Co-grinding, Solubility.
1. Smith JL, Gamal MA, Chremos AN, Graham DY. Famotidine, a new H2-receptor antagonist. Effect on parietal, nonparietal, and pepsin secretion in man. Dig Dis Sci 1985;30(4):308-12.
2. Dammann HG, MÃ¼ller P, Simon B. 24 hour intragastric acidity and single night-time dose of three H-2-blockers. Lancet 1983;2(8358):1078.
3. Fernandes NC, Jagdale SC, Chabukswar AR, Kuchekar BS. Superdisintegrants effect on three model drugs from different BCS classes. Res J Pharm Tech 2009;2(2):335-7.
4. Fahmy RH, Kassem MA. Enhancement of famotidine dissolution rate through liquisolid tablets formulation: In vitro and in vivo evaluation.
Fig. 3: Scanning electron microscopy at magnification Ã—500 of (a) intact famotidine, (b) intact mannitol, (c) physical mixture, and (d) solid dispersion F2
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Fitriani et al.
Eur J Pharm Biopharm 2008;69(3):993-1003.
5. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46(1-3):3-26.
6. Serajuddin AT. Salt formation to improve drug solubility. Adv Drug Deliv Rev 2007;59(7):603-16.
7. Rasenack N, MÃ¼ller BW. Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharm Res 2002;19(12):1894-900.
8. Gupta R, Prajapati SK, Pattnaik S. Performance and evaluation of floating microspheres of famotidine and comparison of their physical properties. Int J Pharm Pharm Sci 2012;4 Suppl 5:376-82.
9. Octavia MD, Halim A, Zaini E. Preparation of simvastatin-Î² cyclodextrin inclusion complexes using co-evaporation technique. J Chem Pharm Res 2015;7(2):740-7.
10. Rangel-Yagui CO, Pessoa A Jr, Tavares LC. Micellarsolubilization of drugs. J Pharm Pharm Sci 2005;8(2):147-63.
11. Salman, Ardiansyah, Nasrul E, Rivai H, Ben ES, Zaini E. Physicochemical characterization of amorphous solid dispersion of ketoprofen-polyvinylpyrorolidone K-30. Int J Pharm Pharm Sci 2014;7(2):209-12.
12. Kalia A, Poddar M. Solid dispersions: An approach towards enhancing dissolution rate. Int J Pharm Pharm Sci 2011;3(4):9-19.
13. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000;50(1):47-60.
14. Yang C, Xu X, Wang J, An Z. Use of the co-grinding method to enhance the dissolution behavior of a poorly water-soluble drug: Generation of solvent-free drug-polymer solid dispersions. Chem Pharm Bull (Tokyo) 2012;60(7):837-45.
15. Chono S, Takeda E, Seki T, Morimoto K. Enhancement of the dissolution rate and gastrointestinal absorption of pranlukast as a model poorly water-soluble drug by grinding with gelatin. Int J Pharm 2008;347(1-2):71-8.
16. Zhong L, Zhu X, Luo X, Su W. Dissolution properties and physical characterization of telmisartan-chitosan solid dispersions prepared by mechanochemical activation. AAPS PharmSciTech 2013;14(2):541-50.
17. Nassab PR, RajkÃ³ R, SzabÃ³-RÃ©vÃ©sz P. Physicochemical characterization of meloxicam-mannitol binary systems. J Pharm Biomed Anal 2006;41(4):1191-7.
18. Zaini E, Witarsah AS, Agustin R. Enhancement of dissolution rate of meloxicam by co-grinding technique using hydroxypropyl methylcellulose. J Chem Pharm Res 2014;6(11):263-7.
19. Muehlenfeld C, Kann B, Windbergs M, Thommes M. Solid dispersion prepared by continuous cogrinding in an air jet mill. J Pharm Sci 2013;102(11):4132-9.
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