Drug distribution and stability in extemporaneous preparations of meloxicam and carprofen after dilution and suspension at two storage temperatures

Michelle G. HawkinsDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

Search for other papers by Michelle G. Hawkins in
Current site
Google Scholar
PubMed
Close
 VMD, DABVP
,
Margo J. KarrikerVeterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616.

Search for other papers by Margo J. Karriker in
Current site
Google Scholar
PubMed
Close
 PharmD
,
Valerie WiebeVeterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616.

Search for other papers by Valerie Wiebe in
Current site
Google Scholar
PubMed
Close
 PharmD
,
Ian T. TaylorDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

Search for other papers by Ian T. Taylor in
Current site
Google Scholar
PubMed
Close
 BS
, and
Philip H. KassDepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616.

Search for other papers by Philip H. Kass in
Current site
Google Scholar
PubMed
Close
 DVM, MPVM, PhD, DACVPM
View More View Less

Abstract

Objective—To determine dispersion uniformity and stability of meloxicam and carprofen in extemporaneous preparations stored for 28 days.

Design—Prospective study.

Sample Population—Meloxicam and carprofen (commercial formulations) were compounded (day 0) with deionized water (DW), 1% methylcellulose gel (MCG), MCG and simple syrup (SS; 1:1 mixture), or a suspending and flavoring vehicle combination (SFVC; 1:1 mixture) to nominal drug concentrations of 0.25, 0.5, or 1.0 mg/mL and 1.25, 2.5, or 5.0 mg/mL, respectively.

Procedures—Preparations were stored at approximately 4°C (39.2°F) or 22°C (71.6°F). For each preparation, drug concentrations were determined and drug stability was evaluated at intervals during storage; on days 0 and 28, pH values were measured and bacterial cultures were initiated.

Results—In meloxicam-DW, meloxicam-MCG (0.25 mg/mL), and meloxicam-MCG (0.5 mg/mL) preparations, drug distribution was uniform (coefficient of variation < 10%); > 90% of the original drug concentration was maintained for 28 days. Despite uniform drug distribution of the carprofen-SFVC preparations, most retained ≥ 90% of the original drug concentration for only 21 days. Use of the MCG-SS combination resulted in foamy preparations of unacceptable variability. After 28 days, pH decreased slightly in meloxicam-DW and meloxicam-MCG preparations (0.17 ± 0.04 and 0.21 ± 0.04, respectively). Carprofen-SFVC (2.5 mg/mL) and carprofen-MCG-SS (5.0 mg/mL) preparations stored at 22°C for 28 days yielded bacterial growth.

Conclusions and Clinical Relevance—DW, MCG, and the SFVC can be used successfully for extemporaneous preparation of meloxicam and carprofen for administration to small exotic animals. Refrigeration is recommended for preparations of meloxicam-DW and carprofen-SFVC.

Abstract

Objective—To determine dispersion uniformity and stability of meloxicam and carprofen in extemporaneous preparations stored for 28 days.

Design—Prospective study.

Sample Population—Meloxicam and carprofen (commercial formulations) were compounded (day 0) with deionized water (DW), 1% methylcellulose gel (MCG), MCG and simple syrup (SS; 1:1 mixture), or a suspending and flavoring vehicle combination (SFVC; 1:1 mixture) to nominal drug concentrations of 0.25, 0.5, or 1.0 mg/mL and 1.25, 2.5, or 5.0 mg/mL, respectively.

Procedures—Preparations were stored at approximately 4°C (39.2°F) or 22°C (71.6°F). For each preparation, drug concentrations were determined and drug stability was evaluated at intervals during storage; on days 0 and 28, pH values were measured and bacterial cultures were initiated.

Results—In meloxicam-DW, meloxicam-MCG (0.25 mg/mL), and meloxicam-MCG (0.5 mg/mL) preparations, drug distribution was uniform (coefficient of variation < 10%); > 90% of the original drug concentration was maintained for 28 days. Despite uniform drug distribution of the carprofen-SFVC preparations, most retained ≥ 90% of the original drug concentration for only 21 days. Use of the MCG-SS combination resulted in foamy preparations of unacceptable variability. After 28 days, pH decreased slightly in meloxicam-DW and meloxicam-MCG preparations (0.17 ± 0.04 and 0.21 ± 0.04, respectively). Carprofen-SFVC (2.5 mg/mL) and carprofen-MCG-SS (5.0 mg/mL) preparations stored at 22°C for 28 days yielded bacterial growth.

Conclusions and Clinical Relevance—DW, MCG, and the SFVC can be used successfully for extemporaneous preparation of meloxicam and carprofen for administration to small exotic animals. Refrigeration is recommended for preparations of meloxicam-DW and carprofen-SFVC.

Contributor Notes

Dr. Karriker's present address is 10435 Sorrento Valley Rd, Ste 101, San Diego, CA 92121.

Supported by a grant from the Association of Avian Veterinarians.

The authors thank Pfizer Animal Health Inc for providing the carprofen analytical standard.

Address correspondence to Dr. Hawkins
  • 1

    Lees P, Landoni MF. Pharmacodynamics and enantioselective pharmacokinetics of racemic carprofen in the horse. J Vet Pharmacol Ther 2002;25:433448.

    • Search Google Scholar
    • Export Citation
  • 2

    Nahata MC, Morosco RS. Stability of lisinopril in two liquid dosage forms. Ann Pharmacother 2004;38:396399.

  • 3

    Wagner DS, Johnson CE, Cichon-Hensley BK, et al. Stability of oral liquid preparations of tramadol in strawberry syrup and a sugar-free vehicle. Am J Health Syst Pharm 2003;60:12681270.

    • Search Google Scholar
    • Export Citation
  • 4

    Henkin CC, Griener JC, Ten Eick AP. Stability of valganciclovir in extemporaneously compounded liquid formulations. Am J Health Syst Pharm 2003;60:687690.

    • Search Google Scholar
    • Export Citation
  • 5

    VandenBussche HL, Johnson CE, Yun J, et al. Stability of flucytosine 50 mg/mL in extemporaneous oral liquid formulations. Am J Health Syst Pharm 2002;59:18531855.

    • Search Google Scholar
    • Export Citation
  • 6

    Johnson CE, Streetman DD. Stability of oral suspensions of ursodiol made from tablets. Am J Health Syst Pharm 2002;59:361363.

  • 7

    Nahata MC, Morosco RS. Stability of tiagabine in two oral liquid vehicles. Am J Health Syst Pharm 2003;60:7577.

  • 8

    Wu AB, Chen CY, Chu SD, et al. Stability-indicating highperformance liquid chromatographic assay method and photostability of carprofen. J Chromatogr Sci 2001;39:711.

    • Search Google Scholar
    • Export Citation
  • 9

    Baert K, De Backer P. Comparative pharmacokinetics of three non-steroidal anti-inflammatory drugs in five bird species. Comp Biochem Physiol C Toxicol Pharmacol 2003;134:2533.

    • Search Google Scholar
    • Export Citation
  • 10

    Thompson KC, Zhao Z, Mazakas JM, et al. Characterization of an extemporaneous liquid formulation of lisinopril. Am J Health Syst Pharm 2003;60:6974.

    • Search Google Scholar
    • Export Citation
  • 11

    Nahata MC. Development of two stable oral suspensions for gabapentin. Pediatr Neurol 1999;20:195197.

  • 12

    Nahata MC, Morosco RS, Trowbridge JM. Stability of propylthiouracil in extemporaneously prepared oral suspensions at 4 and 25 degrees C. Am J Health Syst Pharm 2000;57:11411143.

    • Search Google Scholar
    • Export Citation

Advertisement