JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2016, 65(6):211-215 | DOI: 10.36290/csf.2016.041

Influence of drug concentration and blending technology on the content uniformity of mixture for low dose warfarin tablets

Jan Elbl*, Jan Muselík, Aleš Franc, Jana Mikušová, Zuzana Dolejší, David Vetchý
Ústav technologie léků, Farmaceutická fakulta, Veterinární a farmaceutická univerzita, Brno

Warfarin is a drug with narrow therapeutic index. Individualization of dose and thorough therapy monitoring is compensated by long time use in praxis and low therapy cost. Considering the low dose usually administered, critical parameter of solid dosage form is its uniformity of content. It has to not only meet the criteria set by pharmacopoeia, but to meet them on statisticall significant level also.
This experimental study asseses impact of warfarin concentration and blending time after adition of lubricant on uniformity of content of mixtures and tablets made of them. It concludes, that concentration in 2-2,7% range is optimal and its increase or decrease has a negative effect on uniformity of content. It also confirms 5 minutes of blending after lubricant addition to be adequate, as employing longer blending times leads to mixture overblending.

Keywords: content uniformity; warfarin; blending time; narrow therapeutic index

Received: November 25, 2016; Accepted: December 7, 2016; Published: June 1, 2016  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Elbl J, Muselík J, Franc A, Mikušová J, Dolejší Z, Vetchý D. Influence of drug concentration and blending technology on the content uniformity of mixture for low dose warfarin tablets. Čes. slov. farm. 2016;65(6):211-215. doi: 10.36290/csf.2016.041.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Wardrop D., Keeling D. The story of the discovery of heparin and warfarin. Brit. J. Haem. 2008; 141, 757-763. Go to original source... Go to PubMed...
    2. Cundiff D. K. Insufficient evidence supporting low-intensity warfarin for venous thromboembolism prophylaxis. Med. Gen. Med. 2003; 5(3), 2.
    3. Lawren M. V., Zhanel G. Z. Clinical significance of bioequivalence and interchangeability of narrow therapeutic range drugs: focus on warfarins. J. Pharm. Pharmaceut. Sci. 1998; 3, 92-94.
    4. Jaffer A., Bragg L. Practical tips for warfarin dosing and monitoring. Clev. Clin. J. Med. 2003; 70, 361-371. Go to original source... Go to PubMed...
    5. Warfarin sodium antitrust litigation. United states court of appeals for the third circuit. http://www2.ca3.uscourts.gov/opinarch/023603p.pdf (21. 11. 2016).
    6. Sawoniak A. E., Shalansky A. F., Zed P. J., Sundreji R. Formulary considerations related to warfarin interchangeability. Can. J. Hosp. Pharm. 2002; 55, 215-218.
    7. Franc A., Muselík J. Způsob přípravy pevné lékové formy se sodnou solí warfarinu ve formě klatrátu izopropanolu. VFU Brno. Patent CZ304136 (2. 10. 2013).
    8. Muselík J., Franc A., Doležel P., Goněc R., Krondlová A., Lukášová I. Influence of process parameters on content uniformity of a low dose active pharmaceutical ingredient in a tablet formulation according to GMP. Acta Pharm. 2014; 64, 355-367. Go to original source... Go to PubMed...
    9. Muselík J., Franc A., Štarková J., Matějková Z. Optimalizace technologických postupů pro přípravu tablet s nízkým obsahem warfarinu metodou přímého lisování. Čes. slov. Farm. 2014; 63, 217-221. Go to original source...
    10. Franc A., Muselík J., Máslová R., Hadrabová J. Obsahová stejnoměrnost směsí a tablet obsahujících warfarin. Čes. slov. Farm. 2013; 62, 177-181.

    Return to the content


    Czech and Slovak Pharmacy

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.