Ketoconazole Oral Suspension
»Ketoconazole Oral Suspension contains not less than 1.8g and not more than 2.2g of Ketoconazole in 100mLof 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 á795ñ):
Ketoconazole 2.0g
Cetylpyridinium Chloride 10mg
Xanthan Gum 0.15g
Purified Water 30mL
Suspension Structured Vehicle or
Sugar-Free Suspension Structured Vehicle,a sufficient quantity to make
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 10mLof a solution containing 10mg of Cetylpyridinium Chloride.Transfer this solution,in divided portions,to the mortar containing the powder,and mix to form a smooth paste.Place 20mLof 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 100mL,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 2.55g of tetrabutylammonium hydrogen sulfate in 750mLof water,dilute with acetonitrile to 1000mL,and mix.Pass through a filter having a 5-µm or finer porosity,and degas.Make adjustments if necessary (seeSystem SuitabilityunderChromatography á621ñ).
Resolution solution— Dissolve 4mg of USP Ketoconazole RSin 1.0mLof a solution of potassium sorbate in water (1in 5000),dilute with a mixture of methanol and water (1:1)to 10.0mL,and mix.
Standard preparation— Dissolve an accurately weighed quantity of USP Ketoconazole RSin a mixture of methanol and water (1:1)to obtain a solution having a known concentration of about 0.4mg per mL.
Assay preparation— [NOTE—If the Oral Suspension has settled,invert the container 10to 15times,and sonicate for about 5minutes,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 5.0mLof homogeneous Oral Suspension,freshly mixed and free from air bubbles,to a 250-mLvolumetric flask,add 100mLof water,and stir for 15minutes to dissolve the xanthan gum.Add 135mLof methanol,and stir for an additional 15minutes.Cool,dilute with methanol to volume,and mix.
Chromatographic system(see Chromatography á621ñ)— 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 1mLper minute.Chromatograph theResolution solution,and record the peak responses as directed forProcedure:the relative retention times are about 1.0for ketoconazole and 1.7for 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 forProcedure:the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 5µL)of theStandard preparation and theAssay 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:
in whichCis the concentration,in mg per mL,of USP Ketoconazole RSin theStandard preparation;and rUand rSare the ketoconazole peak responses obtained from theAssay preparation and theStandard preparation,respectively.
Auxiliary Information— Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1098
Pharmacopeial Forum:Volume No.28(2)Page 311
Phone Number:1-301-816-8394