摘要
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.
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 12 sets 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 transferred to 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, but 6 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 from 34.8% 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 the 6 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 12 pharmacies (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.
基金
Supported by Ventrus Biosciences,Inc.,New York,NY,United States
