Evaluation of compounded aqueous milbemycin oxime: issues with formulation potency and reproducibility

• Published in: Journal of small animal practice Vol. 60; no. 1; pp. 27 - 31
• Main Authors: Cochrane, Z. N., Berger, D. J., Viall, A. K., Schrunk, D., (Hans) Coetzee, J. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2019; Wiley Subscription Services, Inc
• Subjects: Administration, Oral; Animals; Drug Compounding - veterinary; Liquid chromatography; Macrolides - analysis; Pharmacy; Prescription Drugs - analysis; Reproducibility; Reproducibility of Results; Storage conditions
• DOI: 10.1111/jsap.12907
• EISSN: 1748-5827
• ISSN: 0022-4510

Objectives
To determine the potency and reproducibility of milbemycin oxime when compounded as an aqueous suspension (20 mg/mL).
Materials and Methods
Preparation choice reflected current prescribing practices. Samples were acquired by prescription from two national veterinary compounding pharmacies at three time points. Two different storage conditions were evaluated and sampled at four time points from the order date (day 7, 14, 21 and 28). Milbemycin oxime recovery was performed by solid‐phase extraction and concentration strength measured via high‐performance liquid chromatography.
Results
The average concentration on day 7 for Pharmacy A samples was 16.29 mg/mL [confidence interval (CI): 15.66 to 16.92] with a coefficient of variation (CV) = 11%, while for Pharmacy B it was 20.46 mg/mL (CI: 19.83 to 21.08) with CV = 22%. The mean decrease in concentration over 28 days for Pharmacy A was 22% (CI: 9% to 34%) while Pharmacy B was 18% (CI: 2% to 35%).
Clinical Significance
The compounded milbemycin oxime suspensions evaluated in this study deviated by more than 10% from their labelled strength in five of the six lots. Clinical efficacy of compounded milbemycin oxime suspensions remains unknown and the use of these products should be discouraged at this time.