Availability, stability, and sterility of pralidoxime for mass casualty use.

STUDY OBJECTIVE: Pralidoxime is indicated to treat patients poisoned with nerve agents. It is available in intravenous formulation for more seriously ill hospitalized patients and intramuscular formulation for field treatment and less seriously ill patients. Our study describes a method to convert the intramuscular formulation for intravenous use and determines the stability and sterility of the resulting formulation over time and under various environmental conditions. METHODS: An inventory was taken of all intravenous (Protopam) and intramuscular (Mark I Autoinjector kits) pralidoxime available in Franklin County, Ohio hospitals, and out-of-hospital stockpiles. A method was devised to safely convert the intramuscular pralidoxime to an intravenous formulation, which was then tested for stability and sterility under a variety of environmental temperatures over time. RESULTS: In Franklin County, Ohio (population 1.1 million), the 10 acute care hospitals and out-of-hospital community have 36 g of intravenous pralidoxime and 4,398 g (7,270 Mark I kits) of intramuscular pralidoxime. The reformulated pralidoxime retained greater than 90% stability and remained sterile at all environmental temperatures through day 28. CONCLUSION: Available pralidoxime in Franklin County is predominantly in the intramuscular preparation. Conversion of intramuscular to intravenous pralidoxime results in a stable and sterile solution for up to 28 days under a variety of environmental conditions and should be considered in a mass casualty situation in which additional intravenous supplies are needed.

Extemporaneous sildenafil citrate oral suspensions for the treatment of pulmonary hypertension in children.

PURPOSE: The stability of sildenafil citrate 2.5 mg/mL in two extemporaneously prepared oral suspensions stored at 4 and 25 degrees C was studied. METHODS: Thirty 25-mg tablets of sildenafil citrate were ground to powder, and the powder was combined with a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of methylcellulose 1% and Simple Syrup, NF, to produce two 2.5-mg/mL suspensions. Five plastic bottles of each suspension were stored in amber plastic prescription bottles at 4 or 25 degrees C. Samples were collected on days 0, 7, 14, 28, 42, 56, 70, and 91 for analysis of sildenafil content by high-performance liquid chromatography; pH was also measured. Samples were visually observed against black and white backgrounds. RESULTS: The mean concentration of sildenafil citrate exceeded 98% of the initial concentration in all samples at both temperatures throughout the 91-day study period. No changes in pH, odor, or physical appearance were observed. CONCLUSION: Sildenafil citrate 2.5 mg/mL in two extemporaneously compounded oral suspensions was stable for 91 days in plastic prescription bottles at 4 and 25 degrees C.

Stability of cefazolin sodium in four heparinized and non-heparinized dialysate solutions at 38 degrees C.

BACKGROUND: Intraperitoneal administration of antibiotics is often required in the treatment of peritoneal dialysis-associated peritonitis. Extended use and heating may affect drug stability. The objective of our study was to determine the stability of cefazolin sodium (125 mg/L and 500 mg/L) in heparinized and non-heparinized dextrosecontaining peritoneal dialysis solution (Dianeal PD-2; Baxter Healthcare, Deerfield, Illinois, USA) containing 1.5%, 2.5%, or 4.25% dextrose, or 7.5% icodextrin, the new colloid formulation (Extraneal; Baxter), at 38 degrees C for 4 days. METHODS: Three poly-vinyl chloride containers of each dialysis fluid were stored at 38 degrees C for 4 days. Samples were taken after the bags were mixed and allowed to stand for 2 minutes. Two 500-microL samples were collected from each bag at hours 0, 12, 24, 36, 48, 60, 72, 84, and 96. Samples were then analyzed by high-performance liquid chromatography (HPLC) in our laboratory. In order to establish the stability-indicating nature of the method, drugs 1.0 mg/mL, vehicles, and their mixtures were subjected to a forced degradation. This is done by acid (2.0 mol/L HCl) and base (2.0 mol/L NaOH) hydrolysis, oxidation (H(2)O(2) 0.3%), and heat at 80 degrees C. Samples were analyzed every 30 minutes until approximately 25% of the drug's peak disappeared. The drug was considered stable if its concentration exceeded 90% of the original. RESULTS: For all Dianeal PD-2 peritoneal dialysis solution containing 1.5%, 2.5%, and 4.25% dextrose, cefazolin sodium was considered stable at 38 degrees C for 60 hours at low cefazolin concentrations (125 mg/L), both with and without heparin, and for 48 hours at high cefazolin concentrations (500 mg/L). Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 48 hours at low cefazolin concentrations in heparinized and non-heparinized solutions, and at high concentrations only in non-heparinized dialysate, not in heparinized dialysate. Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 60 hours at high concentrations when heparinized. CONCLUSION: Cefazolin sodium was stable in all four nonheparinized dialysate fluids for at least 48 hours at 38 degrees C. In heparinized icodextrin dialysate, high concentrations of cefazolin sodium were not stable for extended periods of time. Extended use and heating of dialysate containing cefazolin may adversely affect patient outcome.

Stability of tiagabine in two oral liquid vehicles.

The stability of tiagabine hydrochloride in two extemporaneously prepared oral suspensions stored at 4 and 25 degrees C for three months was studied. Tiagabine is used for adjunctive therapy for the treatment of refractory partial seizures. It is currently available in a tablet dosage form, which cannot be used in young children who are unable to swallow and given doses in milligrams per kilogram of body weight. No stability data are available for tiagabine in any liquid dosage form. Five bottles contained tiagabine 1 mg/mL in 1% methylcellulose:Simple Syrup, NF (1:6), and another five bottles had tiagabine 1 mg/mL in Ora-Plus:Ora-Sweet (1:1). Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating high-performance liquid chromatographic method (n = 15). At 4 degrees C, the mean concentration of tiagabine exceeded 95% of the original concentration for 91 days in both formulations. At 25 degrees C, the mean concentration of tiagabine exceeded 90% of the original concentration for 70 days in Ora-Plus:Ora-Sweet formulation and for 42 days in 1% methylcellulose:syrup formulation. No changes in pH or physical appearance were seen during this period. The stability data for two formulations would provide flexibility for compounding tiagabine. Tiagabine hydrochloride 1 mg/,mL in extemporaneously prepared liquid dosage forms and stored in plastic bottles remained stable for up to three months at 4 degrees C and six weeks at 25 degrees C.

Extended stability of iobenguane under simulated clinical conditions.

PURPOSE: The stability of iobenguane sulfate stored at 4-7 degrees C over 91 days was studied. METHODS: An iobenguane sulfate solution at a concentration of 2.2 mg/mL was prepared in a top-fill i.v. bag using 143 mg of iobenguane sulfate and 65 mL of Sterile Water for Injection, USP. The solution was poured through a 0.22- microm filter assembly for sterilization into 60 1-mL polycarbonate plastic syringes. Each syringe was filled with 0.9 mL of the iobenguane sulfate solution and stored in amber plastic bags at 4-7 degrees C. The stability of iobenguane sulfate was analyzed using high-performance liquid chromatography immediately after solution preparation and on days 7, 14, 28, 42, 56, 70, and 91. Samples were inspected for chemical purity by observing for particulate formation and color change. RESULTS: The mean concentration of ioben-guane exceeded 93% of the initial concentration in all samples throughout the 91-day study period. No changes in color or turbidity were observed. CONCLUSION: Iobenguane sulfate 2.2 mg/mL was stable for 91 days when stored in polycarbonate syringes at 4-7 degrees C.

Stability of sotalol in two liquid formulations at two temperatures.

BACKGROUND: Sotalol is used in certain pediatric patients to treat, suppress, or prevent the recurrence of life-threatening ventricular arrhythmias. However, it is commercially unavailable in a liquid dosage form. The use of an extemporaneously prepared liquid dosage form must be supported by the documentation of the chemical and physical stability of sotalol. OBJECTIVE: To determine the stability of sotalol hydrochloride extemporaneously prepared from tablets in 2 oral suspensions stored at 2 temperatures. METHODS: Five bottles contained Ora Plus:Ora Sweet (1:1) and the other 5 bottles had 1% methylcellulose:simple syrup NF (1:9), with a sotalol concentration of 5 mg/mL. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating HPLC analytical method (n = 15). RESULTS: At 4 degrees C, the mean concentration of sotalol was at least 98.9% of the original concentration in Ora Plus:Ora Sweet suspension and 95.5% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. At 25 degrees C, the mean concentration of sotalol was >/=95.5% of the original concentration in Ora Plus:Ora Sweet suspension and 94.4% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. The pH did not change substantially during the study period. Further, no changes in physical appearance were seen during the study. CONCLUSIONS: Sotalol hydrochloride can be prepared in either of 2 liquid dosage forms and stored in plastic bottles for 13 weeks at 4 or 25 degrees C without substantial loss of potency.

Stability of lisinopril in two liquid dosage forms.

BACKGROUND: Lisinopril is used in pediatric patients with hypertension. It is not commercially available as a liquid. Little is known about the stability of lisinopril in extemporaneously prepared liquid dosage forms. OBJECTIVE: To determine the stability of lisinopril in 2 oral suspensions stored at 4 and 25 degrees C in plastic prescription bottles. METHODS: Five bottles contained methylcellulose 1%:simple syrup NF (1:13) and the other 5 bottles had Ora Plus-Ora Sweet (1:1) at a lisinopril concentration of 1 mg/mL. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by stability-indicating HPLC analytical method (n = 15). RESULTS: At 4 degrees C, the mean +/- SD concentration of lisinopril remained >95.1 +/- 1.8% of the initial concentration in the methylcellulose formulation and 95.1 +/- 3.2% of the initial concentration in the Ora Plus-Ora Sweet formulation throughout the 91-day study period. At 25 degrees C, the mean concentration of lisinopril remained >92.4 +/- 2.2% of the initial concentration in the methylcellulose formulation for 8 weeks and 95.8 +/- 2.3% of the initial concentration in the Ora Plus-Ora Sweet formulation throughout the 91-day study period. No changes in physical appearance in any samples were seen during this period. CONCLUSIONS: Lisinopril can be prepared in either of 2 liquid dosage forms and stored for at least 13 weeks under refrigeration and 8 weeks at room temperature.

Stability of nifedipine in two oral suspensions stored at two temperatures.

OBJECTIVE: To determine the stability of nifedipine in two oral suspensions stored at 4 degrees C and 25 degrees C in plastic prescription bottles over a 3-month period. DESIGN: Two suspensions were prepared: 1% methylcellulose:simple syrup NF (1:13) stored in ten 2 oz bottles; and Ora Plus:Ora Sweet (1:1) at a nifedipine concentration of 4 mg/mL also stored in ten 2 oz bottles. Five bottles of each formulation were stored at 4 degrees C, and the rest of the bottles were stored at 25 degrees C. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating high-performance liquid chromatography analytic method (n = 15). SETTING: Laboratory. RESULTS: At 4 degrees C, the mean concentration of nifedipine was nearly 100% that of the original concentration in both the Ora Plus-Ora Sweet and the 1% methylcellulose-syrup formulations during the 3-month study period. At 25 degrees C, the mean +/- standard deviation concentration of nifedipine was 98.9% +/- 2.36% of the initial concentration in the Ora Plus-Ora Sweet and 97.4% +/- 2.48% in the 1% methylcellulose-syrup formulation over the 3-month period. No changes in pH or physical appearance were observed. CONCLUSION: Nifedipine can be prepared in two liquid dosage forms and stored for up to 3 months under refrigeration or at room temperature.