Ibuprofen lysinate, quicker and less variable: relative bioavailability compared to ibuprofen base in a pediatric suspension dosage form

Ferrero-Cafiero, Juan M; Gich, Ignasi; Puntes, Montserrat; Martínez, Joan; Ballester, María Rosa; Coimbra, Jimena; Mathison, Yaira; Tarré, Maite; Font, Xavier; Antonijoan, Rosa María

doi:10.5414/cp202368

Cited by 6 publications

(7 citation statements)

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“…In order to enhance the dissolution rate of IBU in the stomach, soft gelatin capsules filled with solubilized IBU [14] or IBU salt conjugates, e.g., IBU-arginine [13,15,16] or IBU-lysine [12,17], are used. In particular, it was shown in healthy volunteers that film-coated tablets had 39% lower C max and 3.2 times higher t max (min) values than soft gel capsules of IBU [14].…”

Section: Introductionmentioning

confidence: 99%

Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility

et al. 2019

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The formulation of arylpropionic acid derivatives (profens), which are poorly soluble Biopharmaceutical Classification System (BCS) Type II drugs, has a strong impact on their therapeutic action. This article shows that heat-treated powder mixtures of free acid profens with high surface area Cladophora cellulose induces drug amorphization and results in enhanced solubility and bioavailability. Similar mixtures produced using conventional low surface area cellulose, i.e., microcrystalline cellulose, does not produce the same effect. The concept is thoroughly described and links the solid-state characterization data, such as differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infra-red spectroscopy, with in vitro dissolution in biorelevant media and in vivo pharmacokinetic analysis in rats. The concept is demonstrated for several substances from the profens group, including ibuprofen (main model drug), ketoprofen, flurbiprofen, and naproxen. The presented approach opens new ways to produce solid dosage forms of profen drugs in their free acidic form as alternatives to existing analogues, e.g., drug-salt conjugates or soft gel liquid capsules.

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Section: Introductionmentioning

confidence: 99%

Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility

et al. 2019

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“…No severe adverse events were reported. Both curves were well characterized; in all cases AUC 0 t covered more than 80% of the AUC 0 ∞ …”

Section: Resultsmentioning

confidence: 88%

“…Both curves were well characterized; in all cases AUC 0 t covered more than 80% of the AUC 0 ∞. 9 Average concentration-time curves for S-ibuprofen, Ribuprofen, and the sum of both enantiomers of test and reference formulations are shown in Figure 1. The summary of pharmacokinetic parameters obtained with both formulations is presented in Table 1.…”

Section: Resultsmentioning

confidence: 89%

“…The study population, clinical study design and treatments, pharmacokinetic sampling, analytical methods, and safety and tolerability assessments are described in a previous publication by Ferrero‐Cafiero et al In summary, 24 healthy volunteers adults (12 females and 12 males) were included and the trial followed a standard bioequivalence design: a randomized, open‐label, single‐dose, balanced, two‐way crossover study conducted in the fasting state. Ethics guidelines and regulations were followed.…”

Section: Methodsmentioning

confidence: 99%

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Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base

et al. 2016

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The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R-ibuprofen and S-ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R-ibuprofen and for S-ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method. The 90% confidence interval (90% CI) that would have been obtained with an achiral bioanalytical method (90% CI: Cmax: 117.69-134.46; AUC0 (t) : 104.75-114.45) would have precluded the conclusion of bioequivalence. This conclusion cannot be generalized to the active enantiomer (90% CI: Cmax : 103.36-118.38; AUC0 (t) : 96.52-103.12), for which bioequivalence can be concluded, and/or the distomer (90% CI: Cmax : 132.97-151.33; AUC0 (t) : 115.91-135.77) for which a larger difference was observed. Chiral bioanalytical methods should be required when 1) the enantiomers exhibit different pharmacodynamics and 2) the exposure (AUC or Cmax ) ratio of enantiomers is modified by a difference in the rate of absorption. Furthermore, the bioequivalence conclusion should be based on all enantiomers, since the distomer(s) might not be completely inert, in contrast to what is required in the current regulatory guidelines. In those cases where it is unknown if the ratio between enantiomers is modified by changing the rate of absorption, chiral bioanalytical methods should be employed unless enantiomers exhibit the same pharmacodynamics. Chirality 28:429-433, 2016. © 2016 Wiley Periodicals, Inc.

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“…Limited data is available on the lysinate formulation of ibuprofen. In 2015 Ferrero-Cafiero et al evaluated the bioavailability of pediatric suspension of lysinate ibuprofen compared to pediatric suspension of standard ibuprofen, in healthy, adult volunteers and found that the rate of absorption of the ibuprofen lysinate suspension is quicker and less variable than that of the ibuprofen base reference suspension and it exhibits a shorter Tmax, which is of particular interest for achieving a rapid and homogeneous analgesic and antipyretic effect 8 . However, to our knowledge, no comparative pharmacokinetic study comparing the early absorption of lysinate ibuprofen and standard ibuprofen in the pediatric population has been carried out so far.…”

Section: F O R P U B L I C a T I O Nmentioning

confidence: 99%

Faster Absorption of Ibuprofen Lysinate Than Standard Ibuprofen Acid in Pediatric Post-Surgical Pain

Fabiano¹,

Calcaterra²,

Mari³

et al. 2022

Pharm Adv

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Surgery represents one of the most painful events that a child may experience. Advanced pharmaceutical formulations, including salts of ibuprofen, were developed to provide faster drug absorption and rapid onset of analgesic effects. The aim of this pilot study was to evaluate the rate of early drug absorption of ibuprofen lysinate (Algidrin ® Pediatrico, FARDI S.A., Barcelona, Spain) compared to standard ibuprofen (MomentKid ® , Aziende Chimiche Riunite Angelini Francesco, Rome, Italy) in children receiving the drug for the treatment of post-surgical pain.Twenty-one children (4-16 years) were enrolled in a randomized, open-label, controlled, pilot study.Patients were randomly assigned to the experimental-group (LYS-group, n=10, treated with the lysinate formulation after surgery) or the standard-group (STAND-group, n=11 treated with standard ibuprofen formulation). Four blood samples (immediately before and 5, 15 and 20 minutes after the oral administration) were collected 48-hours after starting ibuprofen; pain (faces pain scale) and vital parameters (heart rate, blood pressure, oxygen saturation) were also considered.Patients from the LYS-group had significantly higher ibuprofen concentrations at 5 minutes after drug intake compared with those from the STAND-group (11.9±8.6 versus 3.6±3.6 mg/L, p=0.010), with the same trend for all other pharmacokinetic parameters. Remarkably, ibuprofen basal concentrations, were more than doubled in the LYS-versus STAND-group (5.7±7.8 versus 2.1±1.0 mg/L, p=0.141). The LYS-group was also associated with a trend for reduced inter-individual variability in the drug exposure compared with the STAND-group (coefficient of variation of the AUC0-20min: 52% versus 84%. Pain control was also obtained.The use of ibuprofen lysinate was associated with an early fast absorption and reduced pharmacokinetic variability compared to the traditional ibuprofen acid formulation, supporting fast action and an improved clinical response to mild-moderate post-surgical pain in children.

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Ibuprofen lysinate, quicker and less variable: relative bioavailability compared to ibuprofen base in a pediatric suspension dosage form

Cited by 6 publications

References 0 publications

Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility

Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility

Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base

Faster Absorption of Ibuprofen Lysinate Than Standard Ibuprofen Acid in Pediatric Post-Surgical Pain

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