Quality of compounded topical 2% diltiazem hydrochloride formulations for anal fissure

AIM:To investigate the quality of topical 2%diltiazem formulations extemporaneously compounded by retail pharmacies openly offering drug-compounding services.METHODS:A participating healthcare professional wrote 12 prescriptions for compounded 2%diltiazem cream,with 2 refills allowed per prescription.The 12sets of prescriptions were filled,at intervals of 1-2 wk between refills,at 12 different independent retail pharmacies that openly offer drug-compounding services in a major metropolitan region.The 36 resultant preparations,provided as jars or tubes,were shipped,as soon as each was filled,at ambient temperature to the study core laboratory for high-performance liquid chromatography(HPLC)analysis,within 10 d of receipt.For the HPLC analysis,8 different samples of the topical diltiazem,each approximately 1 g in weight,were taken from prespecified locations within each container.To initiate the HPLC analysis,each sample was transferredto a 100 mL volumetric flask,to which methanol was added.The HPLC analysis was conducted in accordance with the laboratory-validated method for diltiazem in cream,ointment,and gel formulations.The main outcome measures were potency(percentage of label claim)and content uniformity of the compounded topical 2%diltiazem formulations.RESULTS:Of the 36 prescriptions filled,30 were packaged in jars and 6 were packaged as tubes.The prescriptions were specifically for cream formulations,but6 of the 12 pharmacies compounded 2%diltiazem as an ointment;for another pharmacy,which had inadequate labeling,the dosage form was unknown.The United States Pharmacopoeia(USP)standard for potency is 90%-115%of label claim.Of the 36 preparations,5(13.89%)were suprapotent and 13(36.11%)were subpotent.The suprapotent prescriptions ranged in potency from 117.2%to 128.5%of label claim,and the subpotent prescriptions ranged in potency from34.8%to 89.8%of label claim.Fourteen(38.9%)preparations lacked content uniformity according to the USP standard of 90%-110%potency and<6%relative standard deviation.Of the 30 formulations packaged in jars,12(40%)lacked content uniformity,while of the6 formulations packaged in tubes,2(33.3%)lacked content uniformity.Nine of the 12 pharmacies(75%)failed USP potency or content-uniformity specifications for at least 1 of the 3 prescription fills.For 5 of the 12pharmacies(41.7%),the mean potency across all three prescription fills was<90%of label claim.CONCLUSION:Patients prescribed topical 2%diltiazem for treatment of anal fissure frequently receive compounded formulations that are misbranded with respect to potency and that lack content uniformity.