AAPS PharmSciTech

, Volume 2, Issue 2, pp 29–37 | Cite as

Method to recover a lipophilic drug from hydroxypropyl methylcellulose matrix tablets

  • Robert O. Williams
  • Matthew A. Sykora
  • Vorapann Mahaguna
Article

Abstract

A reverse-phase high-performance liquid chromatographic (HPLC) method for recovery of the lipophilic drug, alprazolam, from matrix tablets containing the hydrophilic polymer hydroxypropyl methylcellulose (HPMC) was developed. Lipophilic drugs, such as alprazolam, are difficult to completely extract and quantitate from tablets containing HPMC polymer. The percentage of recoveries of alprazolam from placebo powder spiked with alprazolam stock solution and from placebo powder mixed with alprazolam powder were about 100% and 85% to 95%, respectively. The validated method using water to completely dissolve HPMC before the addition of a strong solvent to dissolve and extract the drug from the HPMC solution was shown to be the most reproducible method. Different molecular weight distributions of the HPMC polymer, such as HPMC-K4M and HPMC-K100LV, did not influence the dissolution results of alprazolam using this validated method. Similarly, the excipients composing the matrix tablet formulations, such as dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, calcium sulfate dihydrate, sucrose, dextrose, and lactose monohydrate, did not influence the percent recovery of alprazolam. The recovery method reported herein was shown to be the most efficient to achieve complete recovery of alprazolam from powder blends and tablets containing a variety of excipients and different grades of HPMC.

Keywords

Alprazolam hydroxypropyl methylcellulose HPMC matrix tablet liquid chromatography 

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References

  1. 1.
    Alderman DA. A review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms. Int J Pharm Tech Prod Mfg. 1984;5:1–9.Google Scholar
  2. 2.
    The Dow Chemical Company. Using methocel cellulose ethers for controlled release of drugs in hydrophilic matrix systems. Midland, MI: The Dow Chemical Company; 2000.Google Scholar
  3. 3.
    Budavari S, O’Neil MJ, Smith A, Heckelman PE, Kinneary JK. The Merck index: An encyclopedia of chemicals, drugs, and biologicals, 12th ed. Whitehouse Station, NJ: Merck & Co, Inc; 1996.Google Scholar
  4. 4.
    Kumar V, Banker GS. Chemically modified cellulosic polymers. Drug Dev Ind Pharm. 1993;19:1–31.CrossRefGoogle Scholar
  5. 5.
    Archer WL. Hansen solubility parameters for selected cellulose ether derivatives and their use in the pharmaceutical industry. Drug Dev Ind Pharm. 1992;18:599–616.CrossRefGoogle Scholar
  6. 6.
    Kibbe AH. Handbook of pharmaceutical excipients. 3rd ed. Washington, DC: American Pharmaceutical Association; 2000.Google Scholar
  7. 7.
    The Dow Chemical Company. METHOCEL cellulose ethers. Technical handbook. Midland, MI: The Dow Chemical Company; 1998.Google Scholar
  8. 8.
    Dortune B, Ozer L, Uyanik N. Development and in vitro evaluation of a buccoadhesive pindolol tablet formulation. Drug Dev Ind Pharm. 1998;24:281–288.Google Scholar
  9. 9.
    Dortune B, Gunal N. Release of acetazolamide from swellable hydroxypropylmethylcellulose matrix tablets. Drug Dev Ind Pharm. 1997;23:1245–1249.CrossRefGoogle Scholar
  10. 10.
    Greenblatt DJ, Arendt RM, Abernethy DR, Giles HG, Sellers EM, Shader RI.In vitro quantitation of benzodiazepine lipophilicity relation toin vivo distribution. Br J Anaesth. 1983;55:985–989.CrossRefGoogle Scholar
  11. 11.
    Garzone PD, Kroboth PD. Pharmacokinetics of the newer benzodiazepines. Clin Pharmacokin. 1989;16:337–364.CrossRefGoogle Scholar
  12. 12.
    Carelli V, Di Colo G, Nannipieri E, Serafini MF. Enhancement effects in the permeation of alprazolam through hairless mouse skin. Int J Pharm. 1992;88:89–97.CrossRefGoogle Scholar
  13. 13.
    Carelli V, Di Colo G, Nannipieri E, Serafini MF. Enhancement effect in the percutaneous absorption of alprazolam through human skin in vitro. Drug Dev Ind Pharm. 1994;20:1673–1681.CrossRefGoogle Scholar
  14. 14.
    The United States Pharmacopeial Convention. Alprazolam. In: USP 24/NF 19. Philadelphia: National Publishing; 1999:64–65.Google Scholar
  15. 15.
    Snyder LR, Kirkland JJ, Glajch JL. Completing the method: validation and transfer. In: Snyder LR, Kirkland JJ, Glajch JL., eds. Practical HPLC method development. 2 ed. New York: John Wiley & Sons; 1997: 705.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2001

Authors and Affiliations

  • Robert O. Williams
    • 1
  • Matthew A. Sykora
    • 1
  • Vorapann Mahaguna
    • 1
  1. 1.Division of Pharmaceutics, College of PharmacyThe University of TexasAustin

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