Objective—To determine the concentration of doxycycline compounded from doxycycline hyclate tablets into liquid formulations for oral administration in veterinary species and stored for 28 days.
Sample—Doxycycline hyclate tablets (100 mg) crushed and mixed with a 50:50 mixture of syrup and suspension vehicles for oral administration to produce 3 batches each of 2 doxycycline formulations: 33.3 and 166.7 mg/mL.
Procedures—Formulations were stored, protected from light, at room temperature (22° to 26°C [71.6° to 78.8°F]) and at a controlled cold temperature (refrigerated 2° to 8°C [35.6° to 46.4°F]). Doxycycline was extracted from the formulations, and concentration was measured by high-pressure liquid chromatography on days 0 (date of preparation), 1, 4, 7, 14, 21, and 28. Concentrations were compared with those of a US Pharmacopeial Convention reference standard. Formulation quality at each point was also assessed through color change, formulation consistency, and suspension uniformity.
Results—On days 0, 1, 4, and 7, the concentration of each formulation was within 90% to 110% of the reference standard (range, 93% to 109%), which was deemed acceptable. However, doxycycline concentrations had decreased dramatically by day 14 and remained low for the duration of the study period. Doxycycline concentrations on days 14, 21, and 28 were all < 20% (range, 14% to 18%) of the reference standard, and the quality of the formulations decreased as well. No effect of storage temperatures on doxycycline concentration was identified.
Conclusions and Clinical Relevance—The concentration of doxycycline, compounded from commercial tablets in the vehicles evaluated to yield doses of 33.3 and 166.7 mg/mL, cannot be assured beyond 7 days.
Objective—To determine the effects of temperature and light over a 35-day period on stability of pergolide mesylate after compounding in an aqueous vehicle.
Procedures—Pergolide was compounded into a formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at −20°, 8°, 25°, or 37°C without exposure to light or at 25°C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage.
Results—Mean ± SD concentration of pergolide in the formulation immediately after compounding was 1.05 ± 0.086 mg/mL. Samples exposed to light while stored at 25°C had undergone excessive degradation by day 14, samples stored at 37°C had undergone excessive degradation by day 21, and samples stored at 25°C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation.
Conclusions and Clinical Relevance—Results indicated that pergolide mesylate was unstable after compounding in an aqueous vehicle and that storage conditions had an effect on stability of the compounded formulation. Compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used > 30 days after produced. Formulations that have undergone a color change should be considered unstable and discarded.
Objective—To evaluate the stability and retention of viscous formulations of the antifungal drug clotrimazole in vitro and to evaluate retention times, absorption, and histologic response to these compounds when placed in the frontal sinus of dogs.
Animals—6 male Beagles.
Procedures—1% clotrimazole gels were formulated with hydroxypropyl cellulose, poloxamer, and carboxymethylcellulose sodium bases. Commercially available 1% clotrimazole creams were also evaluated. Each compound was incubated at 37°C in a funnel. Volume retained and clotrimazole stability were evaluated for 4 weeks. Six compounds were then chosen for in vivo evaluation. The frontal sinuses of 6 dogs were filled with 1 of the 6 compounds. Computed tomographic evaluation was performed weekly for up to 4 weeks to evaluate gel retention. Blood samples were collected to evaluate clotrimazole absorption. Following euthanasia, sinuses were examined histologically.
Results—Commercially available clotrimazole creams were not retained in funnels in vitro. In vivo, hydroxypropyl cellulose– and carboxymethylcellulose-based gels resulted in the most severe inflammatory response and were retained the longest. Poloxamer-based gels had a shorter retention time and were associated with less inflammation. Clotrimazole was minimally absorbed. Despite a marked inflammatory response to several of the clotrimazole-containing gels, no notable adverse clinical responses were observed.
Conclusions and Clinical Relevance—Poloxamer gels had the most promise for improving drug contact within the frontal sinus of dogs, while limiting the inflammatory response. Poloxamer gels have the additional benefit of improved handling as a result of reverse gelation (ie, they gel when warmed to 37°C).
OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media.
SAMPLE 6 carboplatin-containing carrier media.
PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen.
RESULTS Peak release of carboplatin from the poloxamer copolymer gel and hemostatic gelatin sponge were achieved after 4 and 20 hours, respectively. Maximum release did not differ significantly between the poloxamer copolymer gel and hemostatic gelatin sponge, but both released significantly more carboplatin within 96 hours than did both of the commercial calcium sulfate products. The poloxamer copolymer gel released 99% of the carboplatin, and the hemostatic gelatin sponge released 68.5% of the carboplatin. Peak release of carboplatin from the calcium sulfate beads was not reached within 96 hours.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, carboplatin release from the hemostatic gelatin sponge was incomplete. The poloxamer copolymer gel and hemostatic gelatin sponge released carboplatin rapidly in vitro, whereas calcium sulfate beads did not.
Objective—To determine opinions of faculty members with clinical appointments, clinical veterinarians, residents, and interns at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections.
Procedures—An online questionnaire was sent to all veterinarians with clinical service responsibilities at the North Carolina State University veterinary teaching hospital (n = 167). The survey included 23 questions regarding demographic information, educational experiences, current prescribing practices, and personal opinions related to antimicrobial selection, antimicrobial use, restrictions on antimicrobial use, and antimicrobial resistance.
Results—Of the 167 veterinarians eligible to participate, 71 (43%) responded. When respondents were asked to rate their level of concern (very concerned = 1; not concerned = 5) about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of 1, with mean score for all respondents being 1.5. Most survey participants rated their immediate colleagues (mean score, 1.9) as more concerned than other veterinary medical professionals (mean score, 2.3) and their clients (mean score, 3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable prescribing at least one class of antimicrobials (eg, carbapenems or glycopeptides) because of public health concerns.
Conclusions and Clinical Relevance—Findings indicated that veterinarians at this teaching hospital were concerned about antimicrobial resistance, thought antimicrobials were overprescribed, and supported restricting use of certain antimicrobial classes in companion animals. Findings may be useful in educating future veterinarians and altering prescribing habits and antimicrobial distribution systems in veterinary hospitals.