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Category Antibacterial.

          Cloxacillin Sodium Capsules contain the equivalent of not less than 92.5 per cent and not more than 107.5 per cent of the labelled amount of C₁₉H₁₈ClN₃O₅S.

Strengths available 250 and 500 mg (base).

Dose Adults and children weighing more than 20 kg: 250 to 500 mg every 6 hours taken on an empty stomach.
          Children up to 20 kg of body weight: 6.25 to 12.5 mg per kg of body weight every 6 hours taken on an empty stomach.

Contra-indication; Warning; Precaution See under Penicillin V Potassium, p. 140.

Additional information It is a preferred drug for the treatment of mild to moderate Staphylococcal infections of the skin and soft tissue, respiratory and genitourinary tracts, and joints.
          See also under Penicillin V Potassium, p. 140.

Packaging and storage Cloxacillin Sodium Capsules shall be kept in tightly closed containers.

Labelling The label on the container states the quantity equivalent to the amount of cloxacillin.

Identification
          A. The infrared absorption spectrum of the capsule contents is concordant with the spectrum obtained from Cloxacillin Sodium RS (Appendix 2.1) or with the reference spectrum of Cloxacillin Sodium.
          B. Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using a silanized silica gel H as the coating substance and a mixture of 3 volumes of acetone and 7 volumes of a 15.4 per cent w/v of solution of ammonium acetate, adjusted to pH 5.0 with glacial acetic acid as the mobile phase. Apply separately to the plate, 1 μl of each of the following solutions. For solution (A), shake a quantity of the capsule contents, containing 250 mg of cloxacillin sodium, with 50 ml of water, filter and use the clear filtrate. For solution (B), dissolve 25 mg of Cloxacillin Sodium RS in 5 ml of water and for solution (C), dissolve 25 mg of each of Cloxacillin Sodium RS, Dicloxacillin Sodium RS and Flucloxacillin Sodium RS together in
5 ml of water. After removal of the plate, allow it to dry in air and expose it to iodine vapour until the spots appear. Examine the chromatogram in daylight. The principal spot in the chromatogram obtained from solution (A) corresponds to that in the chromatogram obtained from solution (B). The test is valid only if the chromatogram obtained from solution (C) shows three distinctly separated spots.
          C. Capsule contents yield the reactions characteristic of sodium salts (Appendix 5.1).

Water Not more than 5.0 per cent w/w (Karl Fischer Method, Appendix 4.12).

Dissolution Carry out the test as described in the “Dissolution Test” (Appendix 4.24).
          Dissolution medium: water; 900 ml.
          Apparatus 1: 100 rpm.
          Time: 45 minutes.
          Procedure Determine the amount of cloxacillin (C₁₉H₁₈ClN₃O₅S) of a filtered portion of the test solution, suitably diluted with Dissolution medium, if necessary, as described in the Assay in comparison with a standard solution having a known concentration of Cloxacillin Sodium RS in the same medium.
          Tolerances Not less than 75 per cent (Q) of the labelled amount of C₁₉H₁₈ClN₃O₅S is dissolved in 45 minutes.
Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
          Mobile phase Prepare a mixture of 25 volumes of acetonitrile and 75 volumes of a 0.27 per cent w/v solution of potassium dihydrogenphosphate adjusted to pH 5.0 with dilute sodium hydroxide TS. Make adjustments if necessary.
          Resolution solution Dissolve an accurately weighed quantity of each of Cloxacillin Sodium RS and Flucoxacillin Sodium RS in Mobile phase and dilute quantitatively to obtain a solution having known concentrations of about 100 μg per ml.
          Standard preparation Dissolve an accurately weighed quantity of Cloxacillin Sodium RS in Mobile phase and dilute quantitatively to obtain a solution having a known concentration of about 1.1 mg per ml.
          Assay preparation Remove as completely as possible, the contents of not less than 20 Cloxacillin Sodium Capsules and weigh accurately. Mix the combined contents, and transfer an accurately weighed quantity, containing about 50 mg of cloxacillin, to a 50-ml volumetric flask. Add 40 ml of Mobile phase,shake for 15 minutes and add Mobile phase to volume. Filter and dilute 5.0 ml of the solution to 50.0 ml with Mobile phase.
          Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (5 μm), (b) Mobile phase at a flow rate of about 1.0 ml per minute, and (c) an ultraviolet photometer set at 225 nm.
          To determine the suitability of the chromatographic system, chromatograph Standard preparation, and record the peak responses as directed under Procedure: the resolution factor between cloxacillin (the first peak) and flucloxacillin (the second peak) is not less than 2.5.
          Procedure Separately inject equal volumes (about 20 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.
          Calculation Calculate the content of C₁₉H₁₈ClN₃O₅S in the portion of the Capsules taken, using the declared content of C₁₉H₁₈ClN₃O₅S in Cloxacillin Sodium RS.

Other requirements Comply with the requirements described under “Capsules” (Appendix 1.16).