Ibuprofen absorption rates

The differences in absorption rate and bioavailability between the tablets prepared with the differing batches of ibuprofen are clearly evident despite the fact that their in vitro dissolution profiles can be practically superimposed when tested according to the USP XXI ibuprofen Tablets monograph. 

F. Jamali, N. N. Singh, E M. Easutto, R. T. Courts, and A. S. Russell, "Pharmacokinetics of ibuprofen enantiomers in man following oral administration of tablets with different absorption rates," Pharm. Res., 5 40-43 (1988), R. T. Foster, E Jamali, A. S. Russell, and S. R. AlbeUa, "Pharmacokinetics of ketoprofen enantiomers in young and elderly arthritic patients following single and multiple doses," ]. Pharm. ScL, 77 191-195 (1988). 

Fig. 10 Comparison of absorption rates of ibuprofen from Softgel and tablet.

Jamah, F. Singh, N.N. Pasutto, F.M. Russell, A.S. Coutts, R.T. Pharmacokinetics of ibuprofen enantiomers in humans following oral administration of tablets with different absorption rates. Pharm. Res. 1988, 5, 40-43. 

Similar findings suggesting presystemic GI inversion with ibuprofen have been described by Avgerinos and Hutt [92]. However, a C ax S/R ratio alone does not unequivocally demonstrate inversion this is only demonstrated through an increase in ratio with an increase in 7) ax- Other laboratories have also shown a similar trend of increasing C ax S/R ratio with prolongation of T ax [93]. After administration of racemic ibuprofen to humans, the Tmax values for the enantiomers were found to be identical, but the mean Cmax for the S-ibuprofen exceeded that of the R-isomer [94]. Absorption rate dependency of ibuprofen inversion has also been demonstrated in the rat [95]. Theoretical proof of this presystemic inversion was put forward employing newly developed pharmacokinetic equations [96]. Furthermore, food-induced reduction of the rate of ibuprofen delivery may mimic the effect of a sustained release preparation and also supports the concept of presystemic GI inversion [97]. 

Sattari, S. Jamali, F. Evidence of absorption rate dependency of ibuprofen inversion in the rat. Chirality 1994, 6, 435-439. 

From physicochemical viewpoints, enantiomers and racemates are often very different from one another. For example, it has been shown that individual enantiomers of ibuprofen have greater water solubility and faster dissolution than their racemates (30). A formulation of S-ibuprofen, therefore, may have more rapid absorption and consequently a shorter onset of analgesia. This is important, as evidence exists in the literature in support of a meaningful relationship between ibuprofen serum concentrations and its analgesic effects (31). Hence, a more rapidly absorbed formulation may provide shorter onset of action, Therefore, as a pain reliever, stereochemically pure NSAIDs may be preferable to their respective race-mates. Furthermore, one may take advantage of the single enantiomer s greater solubility to prepare various soluble formulations of NSAIDs and products with an accelerated dissolution rate. 

A small reduction in ketoprofen absorption occurred with aluminium-magnesium hydroxide, but dexketoprofen, ibuprofen and flurbiprofen were not affected, and naproxen showed a slight increase in rate and extent of absorption. Aluminium phosphate had no effect on ketoprofen absorption. 

Magnesium hydroxide appears to improve the rate of absorption of some acidic NSAIDs (which become more soluble as the pH rises) such as ibuprofen and flurbiprofen. Why this increased the gastric toxicity of ibuprofen in the one pharmacodynamic study is unclear. Sodium bicarbonate appears to have a similar effect on rate of absorption. Aluminium antacids do not produce soluble salts with these NSAIDs, and may therefore reduce the rate/extent of absorption. 

A single-dose, crossover study in 6 healthy fasting subjects found that the simultaneous use of colestyramine 8 g modestly reduced the AUC of a single 400-mg oral dose of ibuprofen by 26% and reduced its maximum serum levels by 34%. The rate of absorption was also reduced. Conversely, colestipol 10 g had no significant effect on the pharmacokinetics of ibuprofen. ... 

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