AAPS PharmSciTech

, 10:1243 | Cite as

Cogrinding as a Tool to Produce Sustained Release Behavior for Theophylline Particles Containing Magnesium Stearate

  • Ali Nokhodchi
  • Ononuju N. Okwudarue
  • Hadi Valizadeh
  • Mohammad N. Momin
Research Article

Abstract

The aim of the present study was to explore the cogrinding technique as a tool to slow down the drug release from capsule formulations. To this end, the physical mixtures of theophylline–magnesium stearate were prepared and subjected to different milling times (1, 15, 30, 120 min). In order to investigate the effect of magnesium stearate concentration on drug release, various concentrations of magnesium stearate (1%, 3%, 5%, and 10%, w/w) were used. The dissolution rate of the drug from coground samples and physical mixtures were determined at pH 6.5 according to USP. The results showed that all coground formulations showed slower release rates than their physical mixture counterparts. The effect of cogrinding time on the drug release was complex. Cogrinding time had no significant effect on drug release when the amount of magnesium stearate was 1% (w/w). When the amount of magnesium stearate was increased from 1% to 3% and cogrinding time increased from 1 to 5 min, there was a significant reduction in drug release. Beyond 5-min cogrinding, the drug release increased again. For coground samples containing 5% or 10% (w/w) magnesium stearate, generally, the highest drug release was obtained at higher cogrinding time. This was due to a significant increase in surface area of particles available for dissolution as proven by scanning electron microscopy results. Fourier transform infrared and differential scanning calorimetry results ruled out any significant interaction between theophylline and magnesium stearate in solid state.

Key words

cogrinding dissolution grinding time magnesium stearate ratio of drug to carrier solid-state characterization 

Reference

  1. 1.
    Vogt M, Kunath K, Dressman JB. Cogrinding enhances the oral bioavailability of EMD 57033, a poorly water soluble drug in dogs. Eur J Pharm Biopharm. 2008;68:338–45.CrossRefPubMedGoogle Scholar
  2. 2.
    Barzegar-Jalali M, Nayebi AM, Valizadeh H, Hanaee J, Barzegar-Jalali A, Adibkia K, et al. Evaluation of in vitro–in vivo correlation and anticonvulsive effect of carbamazepine after cogrinding with microcrystalline cellulose. J Pharm Pharmaceut Sci. 2006;9:307–16.Google Scholar
  3. 3.
    Nakai Y, Nakajima S, Yamamoto K, Terada K, Konno T. Effects of grinding on the physical and chemical properties of crystalline medicinals with microcrystalline cellulose. IV. Chem Pharm Bull. 1980;28:652.PubMedGoogle Scholar
  4. 4.
    Sawayanagi Y, Nambu N, Nagai T. Enhancement of dissolution properties of prednisolone from ground mixtures with chitin or chitosan. Chem Pharm Bull. 1983;31:2507–9.Google Scholar
  5. 5.
    Yamamoto K, Nakano M, Arita K, Takayama Y, Nakai Y. Dissolution behavior and bioavailability of phenytoin from a ground mixture with microcrystalline cellulose. J Pharm Sci. 1976;65:1484.CrossRefPubMedGoogle Scholar
  6. 6.
    Vogt M, Kunath K, Dressman JB. Dissolution improvment of four poorly water soluble drugs by cogrinding with commonly used excipients. Eur J Pharm Biopharm. 2008;68:330–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Vogt M, Kunath K, Dressman JB. Dissolution enhancement of fenofibrate by micronization, cogrinding and spray-drying: comparison with commercial preparations. Eur J Pharm Biopharm. 2008;68:283–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Shokri J, Hanaee J, Barzegar-Jalali M, Changizi R, Rahbar M, Nokhodchi A. Improvement of the dissolution rate of indomethacin by a cogrinding technique using polyethylene glycols of various molecular weights. J Drug Del Sci Tech. 2006;16:203–9.Google Scholar
  9. 9.
    Nokhodchi A, Javadzadeh Y, Siahi MR, Barzegar-Jalali M. The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (indomethacin) from liquisolid compacts. J Pharm Pharmaceut Sci. 2005;8:18–25.Google Scholar
  10. 10.
    Nokhodchi A, Talari R, Valizadeh H, Barzegar-Jalali M. An investigation on the solid dispersions of chordazepoxide. Int J Biomed Sci. 2007;3:211–7.Google Scholar
  11. 11.
    Liversidge GG, Cundy KC. Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int J Pharm. 1995;125:91–7.CrossRefGoogle Scholar
  12. 12.
    Yang KY, Glemza R, Jarowski CI. Effects of amorphous silicon dioxides on drug dissolution. J Pharm Sci. 1979;68:560–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Watanabe T, Ohno I, Wakiyama N, Kusai A, Senna M. Controlled dissolution properties of indomethacin by compounding with silica. STP Pharma Sciences. 2002;12:363–7.Google Scholar
  14. 14.
    Bahl D, Hudak J, Bogner R. Comparison of the ability of various pharmaceutical silicates to amorphize and enhance dissolution of indomethacin upon co-grinding. Pharm Dev Technol. 2008;13:255–69.CrossRefPubMedGoogle Scholar
  15. 15.
    Bahl D, Bogner RH. Amorphization alone does not account for the enhancement of solubility of drug co-ground with silicate: the case of indomethacin. AAPS Pharm Sci Tech. 2008;9:146–53.CrossRefGoogle Scholar
  16. 16.
    Durig T, Fassihi R. Mechanistic evaluation of binary effects of magnesium stearate and talc as dissolution retardants at 85% drug loading in an experiment. J Pharm Sci. 1997;86:1092–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Khan KA. Concept of dissolution efficiency. J Pharm Pharmacol. 1975;27:48–9.PubMedGoogle Scholar
  18. 18.
    Nokhodchi A, Khaseh P, Ghafourian T, Siahi-Shadbad MR. The role of various surfactants and fillers in controlling the release rate of theophylline from HPMC matrices. STP Pharma Sciences. 1999;9:555–60.Google Scholar
  19. 19.
    Li-Hua W, Chowhan ZT. Drug–excipient interactions resulting from powder mixing. V. Role of sodium lauryl sulphate. Int J Pharm. 1990;60:61–78.CrossRefGoogle Scholar
  20. 20.
    Pyramides G, Robinson JW, Zito SW. The combined use of DSC and TGA for the thermal analysis of atenolol tablets. J Pharm Biomed Anal. 1995;13:103–10.CrossRefPubMedGoogle Scholar
  21. 21.
    Oliveira GG, Ferraz HG, Matos JSR. Thermoanalytical study of glibenclamide and excipients. J Therm Anal Calorimetry. 2005;79:267–70.CrossRefGoogle Scholar
  22. 22.
    Marini A, Berbenni V, Moioli S, Bruni G, Cofrancesco P, Margheritis C, et al. Drug–excipient compatibility studies by physico-chemical techniques—the case of indomethacin. J Therm Anal Calorimetry. 2003;73:529–45.CrossRefGoogle Scholar
  23. 23.
    Verma RK, Garg S. Compatibility studies between isosorbide mononitrate and selected excipients used in the development of extended release formulations. J Pharm Biomed Anal. 2004;35:449–58.CrossRefPubMedGoogle Scholar
  24. 24.
    Cunha-Filho MSS, Martínez-Pacheco R, Landín M. Compatibility of the antitumoral β-lapachone with different solid dosage forms excipients. J Pharm Biomed Anal. 2007;45:590–8.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Ali Nokhodchi
    • 1
  • Ononuju N. Okwudarue
    • 1
  • Hadi Valizadeh
    • 2
  • Mohammad N. Momin
    • 1
  1. 1.Medway School of PharmacyUniversity of KentKentUK
  2. 2.Faculty of Pharmacy and Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran

Personalised recommendations