title: Quality of compounded topical 2% diltiazem hydrochloride formulations for anal fissure.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Monil Shah, Laura Sandler, Ventrus Biosciences, Inc., New York, NY 10013, United States.
authors.forename: Monil
authors.initials: M
authors.lastname: Shah
authors.forename: Laura
authors.initials: L
authors.lastname: Sandler
authors.forename: Vishwas
authors.initials: V
authors.lastname: Rai
authors.forename: Charu
authors.initials: C
authors.lastname: Sharma
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Raghavan
mesh_terms: D000287:Administration, Topical; D002121:Calcium Channel Blockers / Q000592:standards* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000592:standards* / Q000627:therapeutic use; D004339:Drug Compounding / Q000592:standards*; D005401:Fissure in Ano / Q000188:drug therapy*; D006801:Humans; D010604:Pharmacy / Q000592:standards*
chemical_list: D002121:Calcium Channel Blockers; D004110:Diltiazem
keywords: Anal fissure; Content uniformity; Formulation potency; Pharmacy compounding; Topical diltiazem
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