pH-dependent dissolution behavior of a weakly basic BCS class II drug, clopidogrel

Incecayir T., Olğaç S., Yildiz A., Saar S., Kodan E.

Latin American Journal of Pharmacy, cilt.38, sa.10, ss.1921-1928, 2019 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38 Sayı: 10
  • Basım Tarihi: 2019
  • Dergi Adı: Latin American Journal of Pharmacy
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1921-1928
  • Anahtar Kelimeler: Clopidogrel, Dissolution, Generic, Innovator, Permeability, Similarity
  • Gazi Üniversitesi Adresli: Hayır

Özet

The purpose of this study was to investigate the pH-dependent dissolution of clopidogrel, a poorly soluble weakly basic antiplatelet agent and compare the in vitro dissolution of its innovator and generic products to assess its biopharmaceutical properties. Dissolution tests were carried out using USP Apparatus II with pH 1.2 HCl, pH 4.5 acetate and pH 6.8 phosphate buffers. Based on f2 similarity test, none of the test products exhibited similarity to reference. The physicochemical analysis demonstrated that the unionized fraction (fu) of clopidogrel at jejunal pH 6.0 is similar to that at ileal pH 7.4, explaining clopidogrel’s high and non regional dependent intestinal permeability. Overall, this study indicated complete dissolution of clopidogrel products in stomach, and it is likely to be present in a supersaturated state in the upper intestine, where it is rapidly absorbed before precipitating at the high pH values of the distal regions of the small intestine.