The development of a novel simultaneous in vitro dissolution - in situ perfusion system as a potential tool for studying the absorption of solid oral formulation in rat.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science B.V Country of Publication: Netherlands NLM ID: 9317982 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0720 (Electronic) Linking ISSN: 09280987 NLM ISO Abbreviation: Eur J Pharm Sci Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier Science B.V
      Original Publication: Amsterdam ; New York : Elsevier, c1993-
    • Subject Terms:
      Excipients*/chemistry ; Biopharmaceutics*; Animals ; Rats ; Solubility ; Tablets/chemistry ; Perfusion ; Administration, Oral
    • Abstract:
      The aim of this work is to develop a novel simultaneous in vitro dissolution - in situ perfusion system (SDPS) as a potential tool to evaluate the in vivo performance of solid oral formulation in rat. The innovative nitrendipine (NTD) tablet of Bayotensin mite® made in Germany was used as reference listed drug (RLD), and five generic products from Chinese market were compared with RLD using the in vitro dissolution test method specified by the orange book and the SDPS method developed in this study. Four self-prepared NTD tablets with different proportions of microcrystalline cellulose/starch were employed to investigate the discriminatory ability of the SDPS for formulation. In addition, the predictivity of the SDPS in relation to data from in vivo pharmaceutics studies was evaluated. The 45-min dissolution test and multiple-pH dissolution profiles of generic product 1 and 2 have no difference compared with the RLD, but their dissolution profiles from the SDPS showed statistically significant differences. A biexponential formula successfully described the concentration profiles of self-prepared formulations in SDPS experiments. The k dis (0.08 ± 0.01 ∼ 0.2 ± 0.03 min -1 ) and k a (about 2.30 × 10 -3 min -1 ) values calculated by the formulas of F1-F3 suggested that the used excipients had no effect on the intestinal absorption of NTD, and it might be the property of active pharmaceutical ingredient that led to the difference among the generics. Furthermore, the in vivo rat pharmacokinetics study results of F1-F3 showed a good correlation (R 2  = 0.99) with the SDPS data. In summary, the SDPS is a promising tool to detect the unexpected quality changes of pharmaceutical products in weakly regulated markets, facilitate formulation screening, and potentially reduce animal testing for estimating the in vivo absorption behavior of solid oral formulations. The absorption performance of generic drugs in vivo should be further investigated.
      Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2023. Published by Elsevier B.V.)
    • Contributed Indexing:
      Keywords: Generic drugs; In situ perfusion; In vitro dissolution; Intestinal absorption; Nitrendipine; Oral solid formulation
    • Accession Number:
      0 (Tablets)
      0 (Excipients)
    • Publication Date:
      Date Created: 20231002 Date Completed: 20231106 Latest Revision: 20231106
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.ejps.2023.106601
    • Accession Number:
      37783379