Preliminary study of protamine zinc recombinant insulin for the treatment of diabetes mellitus in cats.

The efficacy of a new protamine zinc formulation based on recombinant insulin (PZIR) was compared with a veterinary-approved beef/pork-source insulin (PZI VET, Idexx Pharmaceuticals) that has been shown to significantly decrease blood glucose in cats with diabetes mellitus (DM). After being examined and weighed and having blood collected for determination of serum fructosamine concentrations, 50 cats with DM and stable glycemic control on PZI VET were switched to PZIR for 30 days at the same dose rate and interval. There was only one reported episode of hypoglycemia, and the cat was withdrawn from the study. In the 47 cats completing the study, there were no significant differences in body weight or serum fructosamine concentrations at days 15 or 30 compared with day 0. The results of this study indicate that PZIR provides glycemic control that is comparable to that of PZI VET when used at the same dose and dosing interval.

Urinary and serum concentrations of diclofenac after topical application to horses.

The liposomal cream formulation of diclofenac, an NSAID, is an effective, safe, and convenient way to treat localized areas of inflammation in horses. The results of this study reveal urinary and serum concentrations of diclofenac following topical administration of 1% liposomal diclofenac cream for 10 days at the labeled dose and at 2X and 4X the labeled dose. These results demonstrate the slow absorption and elimination of 1% liposomal diclofenac cream and may be useful when estimating the withdrawal time needed before a competition in order to prevent an inadvertent positive drug test.

Effect of topical application of diclofenac liposomal suspension on experimentally induced subcutaneous inflammation in horses.

OBJECTIVE: To determine whether 1% diclofenac liposomal suspension (DLS) ointment would be absorbed transdermally and attenuate experimentally induced subcutaneous inflammation in horses. ANIMALS: 7 healthy adult horses. PROCEDURE: Inflammation was produced by injecting 1% sterile carrageenan into subcutaneously implanted tissue cages 8 hours before (time -8) and at the time of application of test ointment. A crossover design was used. Horses received 1 of 2 treatments (topically administered control or DLS ointments) during 48 hours of carrageenan-induced subcutaneous inflammation. A single application of test ointment (7.2 g) was applied over each tissue cage (time 0). Samples of transudate and blood were collected at -8, 0, 6, 12, 18, 24, 30, 36, and 48 hours. Plasma and transudate diclofenac concentrations were determined by use of high-performance liquid chromatography. Transudate concentrations of prostaglandin E2 (PGE2) were determined with a competitive enzyme immunoassay. RESULTS: DLS was absorbed transdermally. The highest concentration (mean +/- SEM, 76.2 +/- 29 ng/mL) was detectable in tissue-cage fluid within 18 hours after application. Minimal concentrations of diclofenac were detectable in plasma. Application of DLS significantly decreased transudate concentrations of PGE2 at 6 and 30 hours. Decreases in PGE2 concentration were observed in the DLS group at all collection times. CONCLUSIONS AND CLINICAL RELEVANCE: A single topical application of DLS resulted in concentrations of diclofenac in transudate within 6 hours and significantly attenuated carrageenan-induced local production of PGE2. Results of this study suggest that DLS is readily absorbed transdermally and may be efficacious for reducing subcutaneous inflammation in horses.

Double-blinded placebo-controlled clinical field trial to evaluate the safety and efficacy of topically applied 1% diclofenac liposomal cream for the relief of lameness in horses.

A topical 1% diclofenac liposomal cream proved to be safe, easy to use, and effective in reducing equine lameness caused by degenerative joint disease. Diclofenac liposomal cream was shown to reduce lameness as graded by owners and veterinarians, regardless of the severity or chronicity of the clinical condition. Topical application allowed for more convenient administration than oral or injectable agents, and no clinically relevant hematologic or serum biochemical changes were noted. The liposomal cream provided a delivery system for diclofenac, an NSAID, to achieve therapeutic levels locally with decreased risk for systemic toxicity and side effects and improved targeting of the painful area.

Effect of terminal sterilization by irradiation on amber Type I and Type III glass containers containing veterinary oxytetracycline suspension.

The purpose of this study is to determine the effect of terminal sterilization by gamma irradiation on 500-mL amber Type I and Type III glass containers (bottles) containing oxytetracycline (OTC) (25% W/V) suspension formulated using 20% (W/V) phospholipids syrup. The formulation was developed for veterinary parenteral administration. The results of terminal sterilization were used to assess the acceptability for this suspension product. OTC is light-sensitive and needs to be stored in amber glass containers. Amber Type I and Type III glass containers were considered for this formulation during development. Type I is a highly resistant, borosilicate glass (oxidized glass). Type III, which is soda-lime glass (reduced glass, see Materials and Methods), may also be used for parenteral products. The amber Type I and Type III glass containers, containing the suspension, were irradiated at 20-40 kGy for 150 min. In order to determine the sterility of the suspension, ampoules of the biological indicator, Bacillus pumilus, were placed in a number of bottles of the suspension. The bottles with the biological indicators were then positioned among the rest of the production bottles as per a radiation dose-mapping study conducted at the sterilization facility. Potency determination and stability evaluations for OTC were performed using high pressure liquid chromatography (HPLC). The results indicate that the gamma irradiation dose of 20-40 kGy for 150 min was able to inactivate 10(6) Bacillus pumilus spores in ampoules. After gamma sterilization, OTC concentration, pH, particle size, endotoxins, and sterility were evaluated. The assay results were comparable for the suspension in amber Type I and Type III glass containers. Sterility and pyrogenicity were measured by the USP Membrane Filtration Method and USP Bacterial Endotoxins Test, respectively. The suspension in the amber Type III glass container was also chemically (HPLC) and physically (suspension mean particle size, viscosity, density, and syringeability) stable for at least 12 months at room temperature. However, amber Type I glass darkened following irradiation, leading to a substantial reduction in glass transparency. The appearance of amber Type III glass was acceptable. Thus, the "reduced" glass, such as soda-lime, was found to be much less susceptible to darkening than the highly oxidized borosilicate amber. Due to the potential aesthetic concerns with Type I glass, the amber Type III glass container was selected for this suspension formulation.

Characteristics of commercially manufactured and compounded protamine zinc insulin.

OBJECTIVE: To evaluate and compare characteristics of a commercially manufactured protamine zinc insulin (PZI) product and PZI products obtained from various compounding pharmacies. DESIGN: Evaluation study. SAMPLE: 112 vials of PZI (16 vials of the commercially manufactured product and 8 vials from each of 12 compounding pharmacies) purchased over an 8-month period. PROCEDURES: Validated methods were used to analyze 2 vials of each product at 4 time points. Appearance, endotoxin concentration, crystal size, insulin concentration in the supernatant, pH, total insulin and zinc concentrations, and species of insulin origin were evaluated. RESULTS: All 16 vials of commercially manufactured PZI met United States Pharmacopeia (USP) specifications. Of 96 vials of compounded PZI, 1 (1 %) contained a concentration of endotoxin > 32 endotoxin U/mL, 23 (24%) had concentrations of insulin in the supernatant > 1.0 U/mL, and 45 (47%) had pH values < 7.1 or > 7.4; all of these values were outside of specifications. Several vials of compounded PZI (52/96 [54%]) did not meet specifications for zinc concentration (0.06 to 0.1 mg/mL for 40 U of insulin/mL, 0.075 to 0.12 mg/mL for 50 U of insulin/mL, and 0.15 to 0.25 mg/mL for 100 U of insulin/mL), and total insulin concentration in 36 [38%] vials was < 90% of the labeled concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Only 1 of 12 compounded PZI products met all USP specifications in all vials tested. Use of compounded PZI insulin products could potentially lead to serious problems with glycemic control in veterinary patients.

Solid-phase extraction and HPLC analysis of methylparaben and propylparaben in a concentrated antibiotic suspension.

An accurate and precise solid-phase extraction coupled with high performance liquid chromatography (SPE/HPLC) method developed for the quantification of antimicrobial preservatives (methylparaben and propylparaben) in oxytetracycline injectable suspension is described in this article. The SPE technique was necessary to quantify the preservatives since the high concentration of the drug and excipients was masking low levels of preservatives, making quantification difficult. This developed HPLC method was stability-indicating and found to be linear between 1.3 to 2.4 mg/mL for methylparaben and 0.15 to 0.27 mg/mL for propylparaben in this concentrated antibiotic suspension formulation. The extraction recoveries were 98.8-101.6%. System precision and sample extraction precision (RSD) were less than 1%.