Dissolution of drug is the rate determining step for oral absorption of the poorly water soluble drugs and solubility is the basic requirement for the absorption of the drug from git. Chitosan, in handbook of pharmaceutical excipients sixth ed, edited by. Because the patch facilitates delivery of ketoprofen over a 24hour period, the drug remains continually present in the tissue adjacent to the site of application. Photocontact allergy to ketoprofen appears to induce a large number of photocross allergies to both structurally similar and. The resulting solution was placed on water bath shaker for 24 hrs. Improvement of the solubility and dissolution of ketoprofen. Ketoprofen has been shown not to induce drug metabolizing enzymes.
Ketoprofen investigated as a drug, hormone, mutagen, primary irritant, and reproductive effector. The objective of the study was to formulate micro particles of a poorly soluble drug ketoprofen. In horses, intravenous dosages of ketoprofen ranging from 0. The nsaids propionic acid derivatives have low water solubility. Pdf solubility and dissolution improvement of ketoprofen. Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bioactives for product development. Ketoprofen is a 23benzolphenylpropionic acid with antiinflammatory, analgesic and antipyretic properties. The solubility was greater in pure etoh and lower in water at all. See what others have said about ketoprofen, including the effectiveness, ease of use and side effects. Enhancing the rate of dissolution or solubility of poorly water soluble drugs is a.
Ketoprofen inhibits the activity of the enzymes cyclooxygenase i and ii, resulting in a decreased formation of precursors of prostaglandins and thromboxanes. Ketoprofen is a propionic acid derivate and nonsteroidal antiinflammatory drug nsaid with antiinflammatory, analgesic and antipyretic effects. Attempts to enhance drug solubility of these therapeutic agents. Ketoprofen is a nonsteroidal antiinflammatory drug nsaid.
Formulation and characterization of ketoprofen emulgels. Ketoprofen is soluble in organic solvents such as ethanol, dmso. Ketoprofen is a nonselective cox inhibitor and nonsteroidal antiinflammatory drug. Ibuprofen, ketoprofen, diclofenac, celecoxib, and etodolac are usually described as practically insoluble in water hydrophobic weakly acidic substances. Ketoprofen ket 23benzoylphenyl propionic acid figure1 is a nonsteroidal antiinflammatory drug nsaids nonselective cox propionic acid derivative 1. Only select registry of toxic effects of chemical substances rtecs data is presented here. Impact of dendrimers on solubility of hydrophobic drug. The ketoprofen regular capsule is also used to treat mild to moderate pain, or menstrual pain. The analysis of the drug solubility at constant temperature in pure solvents or mixtures of cosolvents reveals chemical properties of both solute and solvent. Ketoprofen drug interactions may also occur with medications such as ibuprofen, warfarin, lithium, and corticosteroids. Formulation and characterization of ketoprofen liquisolid. Not all possible interactions are listed in this medication guide.
Find patient medical information for ketoprofen oral on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. This amino sugar glucosamine hcl could be used as a novel. Jun 01, 2019 ketoprofen is 99% bound to plasma proteins, mainly to albumin. The solubility and dissolution rate of poorly watersoluble ketoprofen was improved. List of approved drug products containing ketoprofen in the fda orange book on. Solubility and dissolution improvement of ketoprofen by solid dispersion in polymer and surfactant using solvent evaporation method.
Product monograph ketoprofen ketoprofen capsules bp 50 mg ketoprofen e ketoprofen entericcoated tablets 50 mg and 100 mg ketoprofen sr ketoprofen sustainedrelease tablets. Clinical pharmacokinetics of ketoprofen and its enantiomers. It is used in the treatment of variety of acute and chronic inflammatory. Orudis ketoprofen capsule food and drug administration.
The permeability of ketoprofen through rat skin was increased as the solubility. Bendazac diklofenak etofenamat felbinak flurbiprofen ibuprofen indometacin ketoprofen naproksen piroksikam suprofen cox. Solubility was determined by taking excess quantity of ketoprofen pure drug and prepared formulations in fixed volumes of solvent distilled water0. Formulation and characterization of ketoprofen liquisolid compacts. Ketoprofen is contraindicated for use during pregnancy and breastfeeding. Ketoprofen seda rencber, sinem yaprak karavana, mine ozyazici bioavailability file. It is widely used in the management and treatment of patients with. Ketoprofen should be used with caution in patients with hepatic disease. Ketoprofen exist in the form of tablets to be given by mouth and in the form of a gel to be applied locally on the skin.
Photocontact allergy is a wellknown side effect of topical preparations of the nonsteroidal antiinflammatory drug ketoprofen. Dec, 2012 ketoprofen, a potent nonsteroidal antiinflammatory drug nsaid of the 2arylpropionic acid class, has been used clinically for over 15 years in europe, and has recently been introduced in the united states. For this purpose mobile phase consisting of methaol. Ketoprofen inhibits the activity of the enzymes cyclooxygenase i and ii, resulting in a decreased formation of precursors of. The aim of the present study was to develop a more perfect, accurate and less time consuming method for the estima tion of ketoprofen in human plasma using the c18 col umn with uv. Synthesis and antiinflammatory activity of novel ketoprofen. Ketoprofen is used to treat pain or inflammation caused by arthritis. Ketoprofen is a member of nonsteroidal antiinflammatory drugs and shows strong analgesic and antipyretic effect. The various techniques described above alone or in combination can be used to enhance the solubility of the drugs.
Although it possesses a chiral centre, with only the senantiomer possessing beneficial pharmacological activity, all ketoprofen preparations to date. The epub format uses ebook readers, which have several ease of reading features already built in. The results suggested that lm as a natural solubilizer added promising results in enhancing the solubility and dissolution of the poorly water soluble drugs as kp. Mechanism of photoinduced decomposition of ketoprofen. Elimination the plasma clearance of ketoprofen is approximately 0. Ketoprofen oral capsule is available as a generic drug. Patients with reduced renal function may have conversion of the glucuronide conjugate back to the parent drug.
Learn about drug interactions between ibuprofen oral and ketoprofen oral and use the rxlist drug interaction checker to check drug combinations. Ketoprofen is one of the propionic acid class of nonsteroidal antiinflammatory drugs nsaid with analgesic and antipyretic effects. Physicochemical characterization and in vitro dissolution studies of. Ketoprofen ktp is an antiinflammatory drug widely used in. Ingredient quantity physical description solubility therapeutic activity ketoprofen 10% wv white powder soluble in alcohol, acetone, chloroform antiinflammatory ethoxy diglycol 20% vv clear, unctuous liquid na solvent lecithin isopropyl palmitate solution 22% vv viscous, tan solution na vehicle, surfactant. Sustained release oral drug delivery system an overview ratnaparkhi m. It acts by inhibiting the bodys production of prostaglandin it was patented in 1967 and approved for medical use in 1980. Nonsteroidal antiinflammatory compound that is selective for cox1. Physicochemical characterization and in vitro dissolution.
To enhance the dissolution rate and bioavailability of ketoprofen, a novel dry elixir. Sustained release oral drug delivery system an overview. Aim of the present study was to improve the solubility and dissolution rate of poorly water soluble, bcs classii drug ketoprofen keto by soliddispersion approach. These drug substances are classified in the class 2 of the fdas biopharmaceutics classification system bcs of drugs fda, 2015 due to their low solubility and high permeability. Supernatant was filtered and the concentration of drug in. The glucuronide conjugate of ketoprofen, which can serve as a potential reservoir for the parent drug, is known to be substantially excreted by the kidney. The solubility of ketoprofen and aspirin in subcritical and supercritical co 2 was measured using ftir absorption spectroscopy in the large range of temperature of 298. Solubility enhancement of a poorly aqueous soluble drug.
Tolmetin aspirin is an nsaid medicine but it does not increase the chance of a heart attack. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Uvinduced decarboxylation of the nsaid ketoprofen, followed by activation of molecular oxygen or formation of a decarboxylated peroxide adduct, is explored using computational quantum chemistry. Solubility, the phenomenon of dissolution of solute in solvent to give a homogenous system, is one of the important parameters to achieve desired concentration of drug in systemic circulation for desired anticipated pharmacological response. The kinetic study revealed that, the drug release from all formulations followed zero order kinetics.
Solubility and speciation of ketoprofen and aspirin in. Solid dispersions were prepared by using polyvinylpyrrolidone k30 pvp k30 and dmannitol in different drugs. Journals az books and reference advertising media kit. Ketoprofen is a nonsteroidal antiinflammatory drug nsaid used to treat mild to moderate pain, and helps to relieve symptoms of arthritis osteoarthritis and rheumatoid arthritis, such as inflammation, swelling, stiffness, and joint pain. Solubility of nonsteroidal antiinflammatory drugs nsaids in neat organic solvents and organic solvent mixtures. Examples of drugs having poor bioavailability because of low aqueous solubility drug aqueous solubility mgml absolute bioavailability. Boxbehnken design, dissolution, ketoprofen, liquisolid compacts. Ketoprofen is photolabile and undergoes degradation when irradiated by sunlight to induce various skin diseases 1. Ketoprofen prevents the action of prostaglandin synthetase. This emedtv resource lists some of the drugs that may interact with ketoprofen and describes health problems that some drug interactions may cause. Ketoprofen benzyl alcohol not specified rat 6 mgkgday reproductive toxicity, version.
Formulation of a fastdissolving ketoprofen tablet using freeze. Ketoprofen works by reducing hormones that cause inflammation and pain in the body. Nov 09, 2018 ketoprofen is a nonsteroidal antiinflammatory drug nsaid. Ketofen is a nonnarcotic, nonsteroidal antiinflammatory agent with analgesic and antipyretic properties. Ketoprofen fda prescribing information, side effects and uses. The excited energy surfaces reveal that the neutral species will not decarboxylate, whereas the deprotonated acid decarboxylates spontaneously in the triplet state, and with an. Add the ethoxy diglycol to the ketoprofen in the weigh boat and dissolve the powder.
Although it possesses a chiral centre, with only the senantiomer possessing beneficial pharmacological activity, all ketoprofen preparations to date are marketed as the racemate. Synthesis and antiinflammatory activity of novel ketoprofen and ibuprofen derivatives sadik al mekhlafi 1, hussein alkadi 2 and mohammedi kotb elsayed3 1department of medicinal chemistry, faculty of pharmacy, sanaa university, sanaa, yemen 2department of medicinal chemistry, faculty of medicine, sanaa university, sanaa, yemen. The solubility was more and also the dissolution was rapid for ketoprofen solid dispersions as compare to pure drug. Ketoprofen side effects, dosage, interactions drugs. When ketoprofen is administered with food, its total bioavailability auc is not altered. Ketoprofen is highly bound to plasma proteins, especially albumin. Enhancement of solubility and dissolution of poorly soluble drug. Ketoprofen should be used with caution in patients with renal disease, renal impairment, or renal failure. Pdf enhancement of ketoprofen and ibuprofen solubility and.
Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. Solubility enhancement, physicochemical characterization and. Ketoprofen as a model drug journal of chemical and. Pdf formulation and evaluation of ketoprofen solid. S ketoprofen, a dual cox12 inhibitor, can be used as a nonsteroidal antiinflammatory drug to treat arthritisrelated inflammatory pains. Ketoprofen, a widely prescribed analgesic drug which belongs to bcs class ii and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Ketoprofen has low solubility in water and it is having dissolution problems.
Absorption ketoprofen is rapidly and wellabsorbed, with peak plasma levels occurring within 0. There is evidence for topic ketoprofen for osteoarthritis but not other chronic musculoskeletal pain. The following drug interactions were studied with ketoprofen doses of 200 mgday. Ketoprofen, 100 mg, has been tried as a patch to directly deliver the compound to the site of injury. Improvement of the solubility and dissolution of ketoprofen using natural bile salts mohammed m. The possibility of increased interaction should be kept in mind when orudis ketoprofen doses greater than 50 mg as a single dose or 200 mg of ketoprofen per day are used concomitantly with highly bound drugs. Preparation, solid state characterization and evaluation. The solubility results showed that ketoprofen had significantly more solubility in peg 400 as compared with other nonvolatile solvents used in this study. Natural polymers are used as drug carriers in ionic gelation because of their.
Peak ketoprofen concentrations and free drug auc were increased in older patients see special populations. There are no known active metabolites of ketoprofen. Ketoprofen, a potent nonsteroidal antiinflammatory drug nsaid of the 2arylpropionic acid class, has been used clinically for over 15 years in europe, and has recently been introduced in the united states. Determination of ketoprofen in human plasma by rphplc. Because elderly patients are more likely to have decreased renal function, care. Microspheres verapamil, aspirin, griseofulvin, ketoprofen, iboprufen, terfenadine.
To enhance the solubility and dissolution rate of poorly water soluble drug ketoprofen, selfmicro emulsifying drug delivery system smedds was developed and evaluated. Ketoprofen solubility in organic solvents and aqueous co. Generally, hplc method needs complicated and costly instruments, difficult sample preparation methods and disposal of solvents 11. Pdf solubility and dissolution improvement of ketoprofen by solid. Ketoprofen causes gastrointestinal disturbances, peptic ulceration with bleeding, if present in large doses in gastrointestinal tract upon oral administration singh et al. Other drugs may interact with ketoprofen, including prescription and overthecounter medicines, vitamins, and herbal products. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Ketoprofen ket solubility was determined in fifteen pure solvents and aqueouscosolvent mixtures. We do not recommend storing the aqueous solution for more than one day. Aspirin can cause bleeding in the brain, stomach, and intestines. Ketoprofen was introduced in 1973 in france and the united kingdom for antiinflammatory use. Ketoprofen is mainly excreted in the urine as a glucuronide conjugate. It serves as an efficient drug to treat ankylosing spondylitis, rheumatoid arthritis and osteoarthritis.
Ketoprofen orudis, a highly potent and safe nonsteroidal antiinflammatory drug of the propionic acid derivative group, was synthesized in france by rhonepoulenc chemists in 1967, 3 years after the prototype ibuprofen. Solubility enhancement, physicochemical characterization. Ket being used a nonsteroidal analgesic and antipyretic in argentina in. Potential ketoprofen drug interactions involve medications such as ibuprofen, aspirin, and lithium. Department of pharmaceutics, marathwada mitra mandals college of pharmacy, thergaon kalewadi, pune, india 411033. Ketoprofen should not be used in patients in whom acute asthmatic attacks, urticaria, rhinitis or other allergic.
This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. The stoichiometric ratio determined by phase solubility analysis for inclusion. The objective of the present research is to enhance the aqueous solubility of the poorly water soluble drug ketoprofen by formulation of solid dispersion systems with the use of gelucire 4414 and pvp k30 as a polymer in the formulation. Ketoprofenum pharmacopeia online, drug, pharmaceutical. In the present study a rphplc procedure was developed and validated for the assessment of ketoprofen in human plasma. The patches have been shown to provide rapid and sustained delivery to underlying tissues without significantly increasing levels of drug concentration in the blood when compared to the traditional oral administration. The evolution of the solubility of both active pharmaceutical ingredients apis was fitted using the chrastils equation. As the aim of this study was to enhance the dissolution rate of drug, peg 400 was selected as the suitable nonvolatile solvent in the preparation of ketoprofen liquisolid compacts. Approved drug products containing ketoprofen listed in the fda orange book. While some drug interactions can cause one or both drugs to lose its effectiveness, others may cause bleeding, kidney damage, stomach ulcers, or other serious side effects. It is used in the treatment of variety of acute and chronic inflammatory diseases and. As the concentration of free and thus, biologically active ketoprofen is increased in patients with liver dysfunction and a serum albumin ketoprofen solubility increases with temperature and nonpolar interactions are responsible for this phenomenon.
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