Ketoprofen is a 2-arylpropionic acid derivative non-steroidal antiinflammatory drug (NSAIDs). The chemical name is 2-(3-benzoylphenyl)-propionic acid. The molecular weight of ketoprofen is 254.29 with the empirical formula C16H14O3. The chemical structure is shown in Figure 1.
Physical and chemical properties
• Physical state : white powder
• Odor : Odorless
• Chemical formula : C16H14O3
• Molecular weight : 254.29
• pKa of ketoprofen in water : 4.45
The pKa affects skin permeability because the skin permeability of a drug increases with the increase in the un-ionized fraction. The percentage of un-ionized form at acid mantle of skin pH 4.8 is 30.88. The partition coefficient (log P) of ketoprofen in buffer pH 7.4 is 0.97 and the calculated log P is 2.81. The λmax in ethanol has been reported as 255 nm.
Ketoprofen possess a chiral center but normally used as the racemate (S- and R- enantiomers). The active s-enantiomer is an effective enantiomer for anti-inflammatory of arthritis.
The major band assignments of ketoprofen.
• 3200-2500 : O-H stretching
• 3020 : C-H stretching of aromatic
• 2970, 2930 : C-H stretching of CH3 group (assymetric) masked by O-H stretching
• 2880 : C-H stretching of CH3 group (symmetrical) masked by O-H stretching
• 1695 : C=O stretching of acid
• 1655 : C=O stretching of ketone
• 1595, 1580, 1455 : C=C stretching of aromatic ring
• 1440 : C-H deformation of CH3 (assymetrical)
• 1370 : C-H deformation of CH3 (symmetrical)
• 860-690 : C-H deformation of aromatic ring
Figure 1 : The chemical structure of ketoprofen
Ketoprofen must be kept in a tightly closed container and must be kept away from heating sources, light and water. In powder form, ketoprofen is stable at room temperature. If ketoprofen is heated in an acid solution pH 1 at 98°C for 30 min no decomposition is detected. Exposure of aqueous solutions of ketoprofen to ultraviolet light at 254 nm or daylight for 1 hr at room temperature, was reported to yield (3-benzoylphenyl) ethane which was sequencely converted to (3-benzoylphenyl) ethanol and (3-benzoylphenyl) ethanone.
Ketoprofen shows potent inhibitory effects on prostaglandin synthesis by inhibition of both cyclooxygenase and lipoxygenase. Ketoprofen is used for antiinflammatory and analgesic effects in the symptomatic treatment of acute and chronic rheumatoid arthritis and osteoarthritis. Ketoprofen also is used to relieve mild to moderate pain. In oral dosage form, ketoprofen is rapidly and almost completely absorbed from the GI tract with peak concentration 0.5-2 hr. The usual adult dose of ketoprofen for inflammatory diseases is 150-300 mg daily given in 3-4 divided dose due to the short elimination half-life (1.1-4 hr).
Treatment with ketoprofen can be more effective by providing the oral cavity. However, clinical applications are often limited by adverse effects such as irritation and ulcers of gastrointestine. Since ketoprofen is usually given to patients over an extended period, efforts to reduce its adverse side effects have been attempted. One promising method is to administer the drug via skin. Topical delivery of ketoprofen may provide better patient compliance over oral administration. Topical formulations have been developed for the treatment of acute minor musculoskeletal injuries, sprains, and strains.
Treatment of acute soft tissue injuries using 2.5% ketoprofen gel treatment can be used effectively. Comparison of the efficacy of various NSAIDs in gel formulation was investigated. Ketoprofen gel was significantly superior to piroxicam gel and diclofenac gel in terms of global assessment of treatment response. It improved pain associated with the injury, relieve stiffness and also improved mobility. To develop the transdermal system, the transdermal absorption of various NSAIDs in vitro with human skin was studied. The relative topical effectiveness expected the ration of Jmax/IC50 (the prostaglandin synthesis IC50 value). The larger the ratio was the more likely the bio-effectiveness of the drug following topical administration. Ketoprofen was shown to be the most effective, followed by indomethacin and diclofenac.