ArticleEuropean journal of drug metabolism and pharmacokinetics2016
Enhancement of Dissolution Rate and Intestinal Stability of Clopidogrel Hydrogen Sulfate.
Article in European journal of drug metabolism and pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 19 citations in OpenAlex.
- Compounded Nonsterile Preparations and FDA-Approved Commercially Available Liquid Products for Children: A North American Update.Pharmaceutics · 2022Article
- Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability Enhancement of Poorly Water-Soluble Drugs.Pharmaceutics · 2018Review
- Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid.PloS one · 2017Article
- Hydrogen-Rich Saline Promotes the Recovery of Renal Function after Ischemia/Reperfusion Injury in Rats via Anti-apoptosis and Anti-inflammation.Frontiers in pharmacology · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesClopidogrel is an antiplatelet and antithrombotic prodrug. It has poor oral bioavailability due to poor dissolution and possible premature degradation in the intestine. Accordingly, the objective of this study was to enhance clopidogrel dissolution rate and to reduce its premature degradation in rabbit intestine.
methodsSolid dispersion (SD) systems of clopidogrel with gelucire 50/13 and/or cremophor RH40 were prepared using fusion technique. The SD systems were characterized with respect to drug dissolution. The characterization included thermal analysis and infrared investigations. The stability of clopidogrel in the fluid extracted from small intestinal and colonic mucosal surfaces was monitored both in absence and presence of cremophor or gelucire.
resultsSD formation enhanced drug dissolution with the enhancement increasing at higher concentrations of either cremophor or gelucire. The ternary SD of clopidogrel with cremophor and gelucire reflected synergism between them. This synergism was manifested by enhanced dissolution efficiency of drug to reach 85 % at pH 6.8 and 89 % at pH 7.4 compared to unprocessed drug which liberated 16.2 and 15.2 % at the same pH values, respectively. Enhanced dissolution from SD was mainly due to micellar solubilization for cremophor and was due to change in the crystalline nature of drug with a contribution to self-emulsification in case of gelucire. Clopidogrel showed premature degradation in the intestinal fluid. Cremophor RH 40 reduced this degradation but gelucire failed in this respect.
conclusionThe study introduced SD system for enhanced dissolution rate of clopidogrel with a potential of reduced premature degradation in the intestine.
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