(British Pharmacopoeia 2009) Ketoprofen Gel

General Notices

Action and use Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory. DEFINITION Ketoprofen Gel is a solution of Ketoprofen in a suitable water-miscible basis. The gel complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements. Content of ketoprofen, C16H14O3 92.5 to 107.5% of the stated amount. IDENTIFICATION A. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the principal peak in the chromatogram obtained with solution (2). B. In the test for Related substances, the principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (3). TESTS Acidity or alkalinity pH of a 1% w/v dispersion of the gel in carbon dioxide-free water , 5.0 to 7.5, Appendix V L. Related substances Carry out the method for thin-layer chromatography, Appendix III A, using a silica gel F254 precoated plate (Merck silica gel 60 F254 plates are suitable) and a mixture of 1 volume of formic acid , 25 volumes of toluene and 75 volumes of di-isopropyl ether as the mobile phase. Apply separately to the plate 25 l of each of the following solutions. For solution (1) shake a quantity of the gel containing 40 mg of Ketoprofen with 5 ml of methanol for 15 minutes, centrifuge the mixture for 5 minutes and use the supernatant liquid. Solution (2) contains 0.032% w/v of ketoprofen ethyl ester BPCRS in methanol . Solution (3) contains 0.8 % w/v of ketoprofen BPCRS in methanol . Solution (4) contains 0.004% w/v of ketoprofen BPCRS in methanol . Solution (5) contains 0.0016% w/v of ketoprofen BPCRS in methanol . After removal of the plate, dry it at 105 for 1 hour and examine under ultraviolet light (254 nm). Spray the plate with a 0.4% w/v solution of 2,4-dinitrophenylhydrazine in methanol containing

5% v/v of hydrochloric acid and dry the plate at 105 for 30 minutes. Spray the plate with a mixture of 10 volumes of tetraethylammonium hydroxide solution and 10 volumes of methanol , dry the plate at 105 for 5 minutes and examine in daylight. By each method of visualisation any spot corresponding to ketoprofen ethyl ester in the chromatogram obtained with solution (1) is not more intense than the principal spot in the chromatogram obtained with solution (2) (4%), any other secondary spot is not more intense than the principal spot in the solution (2) (4%), any other secondary spot is not more intense than the principal spot in the chromatogram obtained with solution (4) (0.5%) and not more than three such spots are more intense than the principal spot in the chromatogram obtained with solution (5) (0.2%). ASSAY Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the gel containing 10 mg of Ketoprofen with 50 ml of methanol for 15 minutes, centrifuge the mixture for 5 minutes, dilute 25 ml of the supernatant liquid with sufficient of a mixture of 270 ml of acetonitrile and 550 ml of a 0.5% w/v solution of ammonium acetate to produce 100 ml and mix. For solution (2) add 19 ml of methanol to 5 ml of a 0.1% w/v solution of ketoprofen BPCRS in methanol , add sufficient of a mixture of 270 ml of acetonitrile and 550 ml of a 0.5% w/v solution of ammonium acetate to produce 100 ml and mix. The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 m) (Spherisorb ODS 1 is suitable), (b) as the mobile phase with a flow rate of 2 ml per minute a mixture of 450 volumes of a solution containing 40% v/v of methanol and 60% v/v of acetonitrile and 550 volumes of a 0.5% w/v solution of ammonium acetate, adjusted to pH 5.9 by the addition of 10% w/w nitric acid and (c) a detection wavelength of 254 nm. Calculate the content of C16H14O3 in the gel using the declared content of C16H14O3 in ketoprofen BPCRS. IMPURITIES The impurities limited by the requirements of this monograph include ketoprofen ethyl ester and impurities A, B, E and F listed under Ketoprofen.

Martindale 36 : pg 160, 239

Chloramphenicols
Chloramphenicol is an antibacterial which was first isolated from cultures of Streptomyces venezuelae in 1947 but is now produced synthetically. It has a relatively simple structure and is a derivative of dichloroacetic acid with a nitrobenzene moiety. Chloramphenicol was the first broad-spectrum antibacterial to be discovered; it acts by interfering with bacterial protein synthesis and is mainly bacteriostatic. Its range of activity is similar to that of tetracycline and includes Gram-positive and Gram-negative bacteria, Rickettsia spp., and Chlamydiaceae. The sensitivities of Salmonella typhi, Haemophilus influenzae, and Bacteroides fragilis to chloramphenicol have dictated the principal indications for its use. Shortly after its introduction chloramphenicol was found to have a serious and sometimes fatal depressant effect on the bone marrow. The grey syndrome, another potentially fatal adverse effect, was reported later in neonates. As a result of this toxicity the systemic use of chloramphenicol has been restricted in many countries; it should only be given when there is no suitable alternative and never for minor infections. Chloramphenicol is active when given orally and, unlike most other antibacterials, it diffuses into the CSF even when the meninges are not inflamed. The majority of a dose is inactivated in the liver, only a small proportion appearing unchanged in the urine. Chloramphenicol is widely used for typhoid fever, although resistance is a problem in some countries. For Haemophilus influenzae infections, especially meningitis, the emergence of ampicillin-resistant strains led to a reappraisal of the use of chloramphenicol, and suggestions that ampicillin and chloramphenicol should both be given empirically to patients with meningitis until the sensitivity of the infecting organisms was known, but the newer thirdgeneration cephalosporins are increasingly preferred because of resistance. For proven H. influenzae meningitis, chloramphenicol is used as an alternative to the third-generation cephalosporins, which are now regarded as treatment of choice. Chloramphenicol is also effective against many anaerobic bacteria and may be valuable in such conditions as cerebral abscess where anaerobes such as Bacteroides fragilis are often involved, although metronidazole may be preferred. Chloramphenicol sodium succinate is used parenterally and the palmitate is given orally. Ophthalmic and other topical preparations of chloramphenicol are used widely in some countries. Thiamphenicol is a semisynthetic derivative of chloramphenicol in which the nitro group on the benzene ring has been replaced by a methylsulfonyl group, resulting, in general, in a loss of activity in vitro. It has been claimed that thiamphenicol is less toxic than chloramphenicol and there have been fewer reports of aplastic anaemia but reversible bone-marrow depression may occur more frequently. It is also less likely to cause the grey syndrome. Unlike chloramphenicol, thiamphenicol is not metabolised in the liver to any extent and is excreted largely unchanged in the urine. It has been used similarly to chloramphenicol in some countries. Azidamfenicol is another analogue of chloramphenicol that has been used topically in the treatment of eye infections.

Chloramphenicol (BAN, rINN)