Ibuprofen

IBUPROFEN- ibuprofen suspension
Padagis Israel Pharmaceuticals Ltd

Rx Only

DESCRIPTION

The active ingredient in Ibuprofen Oral Suspension USP, 100 mg/5 mL is ibuprofen, which is a member of the propionic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Ibuprofen is a racemic mixture of [+]S- and [-]R-enantiomers. It is a white to off-white crystalline powder, with a melting point of 74º to 77ºC. It is practically insoluble in water (<0.1 mg/mL), but readily soluble in organic solvents such as ethanol and acetone. Ibuprofen has a pKa of 4.43±0.03 and an n-octanol/water partition coefficient of 11.7 at pH 7.4. The chemical name for ibuprofen is (±)-2-(p-isobutylphenyl) propionic acid. The molecular weight of ibuprofen is 206.28. Its molecular formula is C₁₃ H₁₈ 0₂ and it has the following structural formula:

Ibuprofen Oral Suspension is a sweetened, orange colored, berry flavored suspension containing 100 mg of ibuprofen in 5 mL (20 mg/mL). Inactive ingredients include: anhydrous citric acid, artificial berry flavor, butylparaben, D&C red #33, FD&C yellow #6, glycerin, high fructose corn syrup, hypromellose, polysorbate 80, propylene glycol, purified water, sodium benzoate, sorbitol solution, xanthan gum.

CLINICAL PHARMACOLOGY

Pharmacodynamics –

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that possesses anti-inflammatory, analgesic and antipyretic activity. Its mode of action, like that of other NSAIDs, is not completely understood, but may be related to prostaglandin synthetase inhibition. After absorption of the racemic ibuprofen, the [-]R-enantiomer undergoes interconversion to the [+]S-form. The biological activities of ibuprofen are associated with the [+]S-enantiomer.

Pharmacokinetics –

Ibuprofen is a racemic mixture of [-]R- and [+]S-isomers. In vivo and in vitro studies indicate that the [+]S-isomer is responsible for clinical activity. The [-]R-form, while thought to be pharmacologically inactive, is slowly and incompletely (~60%) interconverted into the active [+]S species in adults. The degree of interconversion in children is unknown, but is thought to be similar. The [-]R-isomer serves as a circulating reservoir to maintain levels of active drug. Ibuprofen is well absorbed orally, with less than 1% being excreted in the urine unchanged. It has a biphasic elimination time curve with a plasma half-life of approximately 2 hours. Studies in febrile children have established the dose-proportionality of 5 and 10 mg/kg doses of ibuprofen. Studies in adults have established the dose-proportionality of ibuprofen as a single oral dose from 50 to 600 mg for total drug and up to 1200 mg for free drug.

Absorption –

In vivo studies indicate that ibuprofen is well absorbed orally from the suspension formulation, with peak plasma levels usually occurring within 1 to 2 hours (see Table 1).

Table 1

Pharmacokinetic Parameters of Ibuprofen Oral Suspension [Mean values (% coefficient of variation)]

Dose	200 mg (2.8 mg/kg) in Adults	10 mg/kg in Febrile Children
Formulation	Suspension	Suspension
Number of Patients	24	18
AUCinf (µg•h/mL)	64 (27%)	155 (24%)
Cmax (µg/mL)	19 (22%)	55 (23%)
Tmax (h)	0.79 (69%)	0.97 (57%)
Cl/F (mL/h/kg)	45.6 (22%)	68.6 (22%)

Legend: AUC_inf = Area-under-the-curve to infinity

T_max = Time-to-peak plasma concentration

C_max = Peak plasma concentration

Cl/F = Clearance divided by fraction at drug absorbed

Antacids –

A bioavailability study in adults has shown that there was no interference with the absorption of ibuprofen when given in conjunction with an antacid containing both aluminum hydroxide and magnesium hydroxide.

H-2 Antagonists –

In studies with human volunteers, coadministration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations.

Food Effects –

Absorption is most rapid when ibuprofen is given under fasting conditions. Administration of ibuprofen oral suspension with food affects the rate but not the extent of absorption. When taken with food, T_max is delayed by approximately 30 to 60 minutes, and peak levels are reduced by approximately 30 to 50%.