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Ketoconazole Oral Suspension
» Ketoconazole Oral Suspension contains not less than 1.8 g and not more than 2.2 g of Ketoconazole in 100 mL of Oral Suspension.
Use Ketoconazole or the number of Ketoconazole Tablets that contain the designated amount of Ketoconazole, and prepare Ketoconazole Oral Suspension as follows (see Pharmaceutical Compounding—Nonsterile Preparations 795):
Ketoconazole 2.0 g
Cetylpyridinium Chloride 10 mg
Xanthan Gum 0.15 g
Purified Water 30 mL
Suspension Structured Vehicle or
Sugar-Free Suspension Structured Vehi-
cle, a sufficient quantity to make		 100 mL
Transfer the Ketoconazole, or Ketoconazole Tablets, to a glass mortar. If Tablets are used, finely powder the Tablets such that they pass through a 40-mesh or 45-mesh sieve, and place the sieved portion in the glass mortar. Dissolve an accurately weighed quantity of Cetylpyridinium Chloride in Purified Water, and dilute quantitatively, and stepwise if necessary, with Purified Water to obtain 10 mL of a solution containing 10 mg of Cetylpyridinium Chloride. Transfer this solution, in divided portions, to the mortar containing the powder, and mix to form a smooth paste. Place 20 mL of Purified Water in a beaker. Using moderate heat, stir to form a vortex, and slowly sprinkle the Xanthan Gum into the vortex to obtain a uniform dispersion. Add the dispersion to the wetted powder paste, and mix until smooth. Add a sufficient quantity of the Suspension Structured Vehicle or Sugar-Free Suspension Structured Vehicle to make a final volume of 100 mL, and mix.
Packaging and storage— Preserve in tight, light-resistant amber containers. Store at controlled room temperature.
Labeling— Label it to state that it is to be well shaken before using and that it is to be protected from light.
Beyond-use date: fourteen days after the day on which it was compounded.
Compliance assay—
Mobile phase— Dissolve 2.55 g of tetrabutylammonium hydrogen sulfate in 750 mL of water, dilute with acetonitrile to 1000 mL, and mix. Pass through a filter having a 5-µm or finer porosity, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Resolution solution— Dissolve 4 mg of USP Ketoconazole RS in 1.0 mL of a solution of potassium sorbate in water (1 in 5000), dilute with a mixture of methanol and water (1:1) to 10.0 mL, and mix.
Standard preparation— Dissolve an accurately weighed quantity of USP Ketoconazole RS in a mixture of methanol and water (1:1) to obtain a solution having a known concentration of about 0.4 mg per mL.
Assay preparation— [NOTE—If the Oral Suspension has settled, invert the container 10 to 15 times, and sonicate for about 5 minutes, or stir on a magnetic stirrer until the suspension appears homogeneous. Examine the mixture for the presence of bubbles and unsuspended solids prior to sampling.] Transfer 5.0 mL of homogeneous Oral Suspension, freshly mixed and free from air bubbles, to a 250-mL volumetric flask, add 100 mL of water, and stir for 15 minutes to dissolve the xanthan gum. Add 135 mL of methanol, and stir for an additional 15 minutes. Cool, dilute with methanol to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 223-nm detector, a 4.6-mm × 25-cm analytical column that contains 5-µm packing L1, and a guard column containing 5-µm packing L1. The column temperature is maintained at 30, and the flow rate is about 1 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for ketoconazole and 1.7 for sorbate; and the resolution, R, between the sorbate and ketoconazole peaks is not less than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 5 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of ketoconazole (C26H28Cl2N4O4) in the portion of Oral Suspension taken by the formula:
250C(rU / rS),
in which C is the concentration, in mg per mL, of USP Ketoconazole RS in the Standard preparation; and rU and rS are the ketoconazole peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Auxiliary Information— Staff Liaison : Behnam Davani, Ph.D., MBA, Senior Scientist
Expert Committee : (MDAA05) Monograph Development-Antivirals and Antimicrobials
USP29–NF24 Page 1216
Pharmacopeial Forum : Volume No. 28(2) Page 311
Phone Number : 1-301-816-8394