PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2001 June; 2(2): 29–37.
Published online 2001 June 6. doi:  10.1208/pt020208
PMCID: PMC2750474

Method to recover a lipophilic drug from hydroxypropyl methylcellulose matrix tablets

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

Full Text

The Full Text of this article is available as a PDF (160K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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.
2. Using methocel cellulose ethers for controlled release of drugs in hydrophilic matrix systems. Midland, MI: The Dow Chemical Company; 2000.
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.
4. Kumar V, Banker GS. Chemically modified cellulosic polymers. Drug Dev Ind Pharm. 1993;19:1–31. doi: 10.3109/03639049309038760. [Cross Ref]
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. doi: 10.3109/03639049209043713. [Cross Ref]
6. Kibbe AH. Handbook of pharmaceutical excipients. 3rd ed. Washington, DC: American Pharmaceutical Association; 2000.
7. METHOCEL cellulose ethers. Midland, MI: The Dow Chemical Company; 1998.
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. [PubMed]
9. Dortune B, Gunal N. Release of acetazolamide from swellable hydroxypropylmethylcellulose matrix tablets. Drug Dev Ind Pharm. 1997;23:1245–1249. doi: 10.3109/03639049709146165. [Cross Ref]
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. doi: 10.1093/bja/55.10.985. [PubMed] [Cross Ref]
11. Garzone PD, Kroboth PD. Pharmacokinetics of the newer benzodiazepines. Clin Pharmacokin. 1989;16:337–364. doi: 10.2165/00003088-198916060-00002. [PubMed] [Cross Ref]
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. doi: 10.1016/0378-5173(92)90306-M. [Cross Ref]
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. doi: 10.3109/03639049409050207. [Cross Ref]
14. USP 24/NF 19. Philadelphia: National Publishing; 1999. Alprazolam; pp. 64–65.
15. Snyder LR, Kirkland JJ, Glajch JL. Completing the method: validation and transfer. In: Snyder LR, Kirkland JJ, Glajch JL., editors. Practical HPLC method development. 2 ed. New York: John Wiley & Sons; 1997. pp. 705–705.

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists