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Preliminary toxicokinetic study with different crystal forms of S (+)-ibuprofen (dexibuprofen) and R,S-ibuprofen in rats.
Arzneimittelforschung. 1997 Jun; 47(6):750-4.A

Abstract

The aim of the study was to gain information on the plasma concentration-time profiles of both ibuprofen (CAS 15687-27-1) enantiomers in the rat after single oral application of two different crystal forms of S (+)-ibuprofen (dexibrufen, CAS 51146-56-6) and racemic ibuprofen in order to optimize blood-sampling times in a subsequent subchronic toxicity study. The application of either commercial racemic ibuprofen or recrystallised S (+)-ibuprofen (60 mg/kg) to two groups of 4 rats per blood sampling term was carried out in order to define Cmax and tmax and AUC of the plasma-concentrations of the ibuprofen enantiomers. The crystals of commercial (manufactured according to an usual manufacturing procedure) and recrystallised (S(+)- and racemic ibuprofen were different in respect to their shape and size. The recrystallised crystal species of S (+)- and racemic ibuprofen has better galenic (tabletting-) properties and tablets containing the modified S (+)-ibuprofen species showed favorable clinical results. The toxicokinetic behaviour of the recrystallised species was investigated in comparison to the commercial crystal species because of its slightly but significantly slower dissolution rate in simulated gastric and enteric juice. As the AUC0-24 h S-(+)-ibuprofen and the AUC0-24 h, R-(-)-ibuprofen after application of commercial and recrystallised crystal species were not different, the crystal form apparently did not exert an influence on the extent of absorption of S-(+)-ibuprofen and racemic ibuprofen in the rat. The rat has a high inversion capacity and the inversion of R-(-)-ibuprofen after application of commercial and recrystallised racemic ibuprofen was nearly complete in this study. The effects of crystallinity on solubility in simulated media in vitro did not correlate to the findings on the extent of absorption in the rat in vivo.

Authors+Show Affiliations

Department of Research and Development, Gebro Broschek GmbH, Fieberbrunn, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

9239454

Citation

Walser, S, et al. "Preliminary Toxicokinetic Study With Different Crystal Forms of S (+)-ibuprofen (dexibuprofen) and R,S-ibuprofen in Rats." Arzneimittel-Forschung, vol. 47, no. 6, 1997, pp. 750-4.
Walser S, Hruby R, Hesse E, et al. Preliminary toxicokinetic study with different crystal forms of S (+)-ibuprofen (dexibuprofen) and R,S-ibuprofen in rats. Arzneimittelforschung. 1997;47(6):750-4.
Walser, S., Hruby, R., Hesse, E., Heinzl, H., & Mascher, H. (1997). Preliminary toxicokinetic study with different crystal forms of S (+)-ibuprofen (dexibuprofen) and R,S-ibuprofen in rats. Arzneimittel-Forschung, 47(6), 750-4.
Walser S, et al. Preliminary Toxicokinetic Study With Different Crystal Forms of S (+)-ibuprofen (dexibuprofen) and R,S-ibuprofen in Rats. Arzneimittelforschung. 1997;47(6):750-4. PubMed PMID: 9239454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preliminary toxicokinetic study with different crystal forms of S (+)-ibuprofen (dexibuprofen) and R,S-ibuprofen in rats. AU - Walser,S, AU - Hruby,R, AU - Hesse,E, AU - Heinzl,H, AU - Mascher,H, PY - 1997/6/1/pubmed PY - 1997/6/1/medline PY - 1997/6/1/entrez SP - 750 EP - 4 JF - Arzneimittel-Forschung JO - Arzneimittelforschung VL - 47 IS - 6 N2 - The aim of the study was to gain information on the plasma concentration-time profiles of both ibuprofen (CAS 15687-27-1) enantiomers in the rat after single oral application of two different crystal forms of S (+)-ibuprofen (dexibrufen, CAS 51146-56-6) and racemic ibuprofen in order to optimize blood-sampling times in a subsequent subchronic toxicity study. The application of either commercial racemic ibuprofen or recrystallised S (+)-ibuprofen (60 mg/kg) to two groups of 4 rats per blood sampling term was carried out in order to define Cmax and tmax and AUC of the plasma-concentrations of the ibuprofen enantiomers. The crystals of commercial (manufactured according to an usual manufacturing procedure) and recrystallised (S(+)- and racemic ibuprofen were different in respect to their shape and size. The recrystallised crystal species of S (+)- and racemic ibuprofen has better galenic (tabletting-) properties and tablets containing the modified S (+)-ibuprofen species showed favorable clinical results. The toxicokinetic behaviour of the recrystallised species was investigated in comparison to the commercial crystal species because of its slightly but significantly slower dissolution rate in simulated gastric and enteric juice. As the AUC0-24 h S-(+)-ibuprofen and the AUC0-24 h, R-(-)-ibuprofen after application of commercial and recrystallised crystal species were not different, the crystal form apparently did not exert an influence on the extent of absorption of S-(+)-ibuprofen and racemic ibuprofen in the rat. The rat has a high inversion capacity and the inversion of R-(-)-ibuprofen after application of commercial and recrystallised racemic ibuprofen was nearly complete in this study. The effects of crystallinity on solubility in simulated media in vitro did not correlate to the findings on the extent of absorption in the rat in vivo. SN - 0004-4172 UR - https://www.unboundmedicine.com/medline/citation/9239454/Preliminary_toxicokinetic_study_with_different_crystal_forms_of_S__+__ibuprofen__dexibuprofen__and_RS_ibuprofen_in_rats_ DB - PRIME DP - Unbound Medicine ER -