Quality control of extemporaneously prepared microdose captopril capsules: weight variation versus content uniformity.
Microdose (1 mg) captopril therapy is commonly used for the initial dose titration in patients with congestive heart failure. Since this dosage form is not commercially available, it has to be extemporaneously compounded. Quality control of each batch is commonly evaluated using the weight variation technique described in the USP. Despite careful titration with microdose, captopril capsules variability in patient's response has been observed. In order to explain this fluctuation, the actual content of extemporaneously compounded microdose captopril capsules was evaluated using a high pressure liquid chromatographic assay. Microdose captopril capsules were prepared by triturating 25 mg tablets with lactose in a mortar using standard geometric dilution technique and a Sharpe-Dohme hand-operated capsule filling machine. Forty-eight microdose captopril capsules were randomly selected from the compounded batch and were individually assayed for captopril amount. The mean +/- standard deviation (SD) amount of captopril in each capsule was 1.27 g +/- 0.31 mg with a range of 0.84 g to 1.96 mg. The coefficient of variation was 24.5%. Ten captopril capsules were randomly selected from the compounded batch and were individually weighed. The capsules had a mean weight +/- SD of 198.3 g +/- 21.2 mg and a coefficient of variation of 7.3%. Even though the extemporaneously prepared microdose captopril capsules were within acceptable limits for weight variation described in the USP, the actual dose administered to the patients could vary by as much as 24.5%.
Colucci
R D
RD
Clinical Pharmacology/Clinical Research, Schering-Plough Research, Institute Kenilworth, NJ 07033.
Scavone
J M
JM
Auty
R
R
Glassner-Cohen
L
L
D002214:Capsules; D002216:Captopril / Q000008:administration & dosage / Q000032:analysis / Q000592:standards*; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000592:standards*; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D011786:Quality Control; D011897:Random Allocation
D002214:Capsules; D002216:Captopril