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Cortisol Acetate 

Category Corticosteroid (topical); anti-inflammatory (steroidal).

Hydrocortisone Acetate contains not less than 96.0 per cent and not more than 104.0 per cent of C₂₃H₃₂O₆, calculated on the dried basis. 

Description White to practically white, crystalline powder; odourless.

Solubility Insoluble in water; slightly soluble in ethanol and in chloroform. 

Contra-indication It is contra-indicated in vaccinia and varicella in the presence of skin infections, acute purulent infections of the eye, fungal infection of the ear, or perforation of the tympanic membrane, herpes simplex of the eye, infectious diseases without anti-infective coverage, active peptic ulcer, myasthenia gravis, or idiopathic thrombocytopenic purpura.

Warning

      1. Topical corticosteroids should not be used in the treatment of acne.

      2. It may mask signs of infection and new infections may appear during its use.

      3. Prolonged use may cause skin atrophy, increased intra-ocular pressure and cataracts, or retard corneal healing.

      4. It may be absorbed in sufficient amount to cause systemic effects especially when applied to large areas, to broken skin, or under occlusive dressing.

      5. It should not be applied to the breasts prior to nursing.

      6. Bandaging or wrapping the treated skin area should be avoided unless directed to do so by a physician.

      7. Tight-fitting diapers or plastic pants should not be used on a child if the diaper area is being treated.

      8. Risk-benefit should be considered if it is to be used in pregnant women.

Packaging and kept storage Hydrocortisone Acetate shall be kept in well-closed containers, protected from light.

Identification

      A. The infrared absorption spectrum is concordant with the spectrum obtained from Hydrocortisone Acetate RS (Appendix 2.1) or with the reference spectrum of Hydrocortisone Acetate.

      B. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation as obtained in the Assay.

      C. It yields the reactions characteristic of acetyl groups (Appendix 5.1).

Melting temperature About 200º, with decomposition (Appendix 4.3).

Specific rotation +158º to +165º, determined in a 0.5 per cent w/v solution in dioxane (Appendix 4.8).

Loss on drying Not more than 0.5 per cent w/w after drying about 500 mg at 105º for 3 hours (Appendix 4.15).

Sulfated ash Negligible, from 100 mg (Appendix 5.3).

Chromatographic purity Carry out the test as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

      Solution A Prepare a mixture of 80 volumes of water and 20 volumes of acetonitrile. Make adjustments if necessary.

      Solution B Prepare a mixture of 70 volumes of acetonitrile and 30 volumes of water. Make adjustments if necessary.

      Mobile phase Use variable mixtures of Solution A and Solution B as directed for Chromatographic system.

      Diluting solution Prepare a mixture of 700 volumes of acetonitrile, 300 volumes of water, and 1 volume of glacial acetic acid. 

      Standard solution Dissolve an accurately weighed quantity of Hydrocortisone Acetate RS in Diluting solution, and dilute quantitatively, and stepwise if necessary, with Diluting solution to obtain a solution having a known concentration of about 5 μg per ml.

      Test solution Transfer about 10 mg of the test substance, accurately weighed, to a 10-ml volumetric flask, dissolve in and dilute with Diluting solution to volume, and mix.

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (3 to 10 μm), (b) Mobile phase at a flow rate of about 1 ml per minute and (c) an ultraviolet photometer set at 254 nm.

 

 

 

 

 

 

 

 

 

      Chromatograph Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5.0 per cent.

      Procedure Separately inject equal volumes (about 10 μl) of Standard solution and Test solution into the chromatograph, record the chromatograms, and measure the peak responses.

      Calculation Calculate the percentage of each impurity in the portion of the test substance taken by the expression:

0.5(r_i /r_s),

in which r_i is the peak response for each impurity, and r_s is the peak response of the Standard solution: not more than 1.0 per cent of any individual impurity is found, and not more than 2.0 per cent of total impurities is found.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

      Mobile phase Prepare a mixture of 475 volumes of butyl chloride, 475 volumes of water-saturated butyl chloride, 70 volumes of tetrahydrofuran, 35 volumes of methanol and 30 volumes of glacial acetic acid. Make adjustments if necessary.

      Standard preparation Dissolve an accurately weighed quantity of Hydrocortisone Acetate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 100 μg per ml. 

      Assay preparation Transfer about 10 mg of Hydrocortisone Acetate, accurately weighed, to a 100-ml volumetric flask, add Mobile phase to volume, and mix.

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm × 4 mm) packed with porous silica particles (10 μm), (b) Mobile phase at a flow rate of about 1 ml per minute and (c) an ultraviolet photometer set at 254 nm.

      To determine the suitability of the chromatographic system, chromatograph Standard preparation, and record the peak responses as directed under Procedure: the symmetry factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0 per cent.

      Procedure Separately inject equal volumes (about 10 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 C₂₃H₃₂O₆ in the Hydrocortisone Acetate taken, using the declared content of C₂₃H₃₂O₆ in Hydrocortisone Acetate RS.