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.     

Characterization of an extemporaneous liquid formulation of lisinopril.

The stability of lisinopril in an extemporaneously prepared suspension stored at or below 25 degrees C for 28 days under ambient light exposure was studied. A formulation of 1-mg/mL oral suspension was prepared from commercially available 20-mg lisinopril tablets, using Bicitra and Ora-Sweet SF as the compounding vehicles to make a final volume of 200 mL. Individual samples, stored in 8-oz amber polyethylene terephthalate bottles, were used for each test performed. All samples were stored at 25 degrees C. Appropriateness of the extemporaneous preparation method was performed by shaking three lots of each suspension for 30, 60, and 90 seconds. To test the robustness and reproducibility of the method, two chemists prepared the suspensions from the same three lots of lisinopril tablets. Chemical and physical stability were established by analyzing duplicate samples at time zero and after one, two, four, and six weeks. The solubility of lisinopril was tested from suspensions stored for four weeks. In-use stability was also examined over four weeks. Photochemical stability was examined by exposing three batches of the suspension to maximum light stress in accordance with the International Conference on Harmonization. Antimicrobial-effectiveness testing was also conducted with freshly prepared suspensions and suspensions stored for six weeks. The preparation method used was appropriate and effective. Lisinopril is fully dissolved in the suspension matrix. Satisfactory chemical, physical, and microbiological results were obtained after the suspensions were stored for six weeks at 25 degrees C and 35% relative humidity. Lisinopril suspensions extemporaneously prepared from tablets are stable for at least four weeks when stored at or below 25 degrees C under ambient light exposure.     

Stability of ganciclovir in extemporaneously compounded oral liquids.

The stability of ganciclovir in extemporaneously prepared sugar-containing and sugar-free oral liquids was studied. The contents of 80 250-mg capsules of ganciclovir were combined with Ora-Sweet or Ora-Sweet SF (sugar free) (Paddock Laboratories) to produce 200 mL of suspension with a ganciclovir concentration of 100 mg/mL. Five 1-mL samples were analyzed immediately, and the rest of the suspension was poured into five 60-mL amber polyethylene terephthalate bottles and stored at 23-25 degrees C. Samples were removed and analyzed with stability-indicating high-performance liquid chromatography on days 15, 35, 60, 91, and 123. The suspensions retained at least 96% of the initial ganciclovir concentration for 123 days. The pH of the suspensions was initially 4.5 and remained unchanged throughout the study. There was no detectable change in color or odor and no visible microbial growth in any sample. Ganciclovir 100 mg/mL was stable for 123 days in sugar-containing and sugar-free oral liquids stored at 23-25 degrees C in amber polyethylene terephthalate bottles.     

Stability of an extemporaneously prepared alcohol-free phenobarbital suspension.

PURPOSE: The physical and chemical short-term stability of alcohol-free, oral suspensions of phenobarbital 10 mg/mL prepared from commercially available tablets in both a sugar and a sugar-free vehicle was assessed at room temperature. METHODS: Phenobarbital oral suspension 10 mg/mL was prepared by crushing 10 60-mg tablets of phenobarbital with a mortar and pestle. A small amount of Ora-Plus was added to the phenobarbital powder to sufficiently wet the particles. A 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF was combined with the phenobarbital powder to produce a final volume of 60 mL. Three identical samples of each of the two different formulations were prepared and stored at room temperature in 2-oz amber plastic bottles. Immediately after preparation and at 15, 30, 60, and 115 days, the samples were assayed in duplicate by stability-indicating high-performance liquid chromatography. The samples were tasted and inspected for color and odor changes. The percent of the initial concentration remaining at each study time for each phenobarbital suspension was determined. Stability was defined as the retention of at least 90% of the initial concentration. RESULTS: There were no detectable changes in color, odor, and taste and no visible microbial growth in any sample. At least 98% of the initial phenobarbital concentration remained throughout the 115-day study period in both preparations. CONCLUSION: An extemporaneously prepared alcohol-free suspension of phenobarbital 10 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet or Ora-Sweet SF was stable for at least 115 days when stored in 2-oz amber plastic bottles at room temperature.     

Stability of dolasetron in two oral liquid vehicles.

The stability of dolasetron 10 mg/mL over 90 days when prepared as an oral liquid formulation from commercially available tablets in both strawberry syrup and a sugar-free vehicle was studied. A liquid suspension of dolasetron mesylate 10 mg/mL was prepared from commercially available dolasetron tablets, OraPlus, and Ora-Sweet or strawberry syrup. Six samples of each formulation were prepared and stored in amber plastic bottles. Three samples of each formulation were refrigerated (3-5 degrees C) and three were stored at room temperature (23-25 degrees C). A 1-mL sample was withdrawn from each of the 12 bottles immediately and after 7, 14, 30, 60, and 90 days. After further dilution to an expected concentration of 10 micrograms/mL with sample diluent, the solutions were assayed in duplicate using high-performance liquid chromatography. The samples were also inspected for color and odor changes, and the pH of each sample was determined. The stability-indicating capability of the dolasetron assay was determined by forced degradation of four separate 10-mg/mL samples exposed to direct sunlight for 90 days. There were no detectable changes in color, odor, or taste and no visible microbial growth in any sample. At least 98% of the initial dolasetron concentration remained throughout the 90-day study period for all samples. An extemporaneously compounded oral liquid preparation of dolasetron mesylate 10 mg/mL in a 1:1 mixture of Ora-Plus and strawberry syrup or Ora-Sweet was stable for at least 90 days when stored at 3-5 or 23-25 degrees C.     

Stability of Adderall in extemporaneously compounded oral liquids.

The short-term stability of Adderall in three extemporaneously compounded oral liquids was studied. Three suspensions of Adderall 1 mg/mL were prepared from commercially available 10-mg Adderall tablets with Ora-Sweet, Ora-Plus, and a 1:1 mixture of Ora-Sweet and Ora-Plus. Each suspension was stored in the dark in a stability chamber at 25 degrees C and 60% relative humidity for 30 days. The stability of the active drug (a mixture of levoamphetamine and dextroamphetamine salts) in each of the three vehicles was determined immediately after preparation and at 10, 20, and 30 days by using gas chromatography-mass spectrometry (GCMS). No significant changes in concentrations of either amphetamine isomer occurred during the 30-day study period. Visual inspection of samples revealed no changes in color or odor. Extemporaneously compounded liquid oral formulations of Adderall 1 mg/mL in Ora-Sweet, Ora-Plus, or a 1:1 mixture of Ora-Sweet and Ora-Plus were stable for at least 30 days at 25 degrees C and 60% relative humidity.     

Stability of codeine phosphate in an extemporaneously compounded syrup.

PURPOSE: The stability of codeine phosphate in an extemporaneously compounded syrup is described. METHODS: Codeine phosphate 3-mg/mL syrup was prepared using commercially available Codeine Phosphate, USP, Sterile Water for Irrigation, USP, and Ora-Sweet syrup vehicle. Samples were stored in amber polyethylene terephthalate bottles with child-resistant caps. A second batch of codeine phosphate 3-mg/mL syrup was prepared and drawn into amber polyethylene oral syringes with silicon elastomer tips. All samples were stored at room temperature and in the dark. Samples were analyzed immediately and at 7, 14, 28, 42, 56, 70, and 98 days. Codeine phosphate concentrations were measured using a modified stability-indicating high-performance liquid chromatographic method. At each test interval, the density of the syrup was determined gravimetrically using a 10-mL amber oral syringe. Excessive degradation was defined as a greater than 7% loss of the initial concentration. RESULTS: The stock internal standard was stable for at least 98 days at room temperature. The compounded syrup retained more than 93% of the initial codeine phosphate concentration for at least 98 days at 22-25 degrees C. No changes in color, clarity, or odor and no visible solids or microbial growth were observed in any sample. The pH of the syrup was initially 4.2 and remained unchanged throughout the study. CONCLUSION: Codeine phosphate 3 mg/mL in Ora-Sweet syrup vehicle was stable in both amber polyethylene terephthalate bottles and amber polyethylene oral syringes for at least 98 days when stored at 22-25 degrees C and protected from light.     

Stability and viscosity of a flavored omeprazole oral suspension for pediatric use.

PURPOSE: The stability and viscosity of preparations of a commercially available, flavored, immediate-release powder for oral suspension (omeprazole-sodium bicarbonate) during refrigerator and room temperature storage were investigated. METHODS: Omeprazole-sodium bicarbonate 20-mg packets were suspended to initial omeprazole concentrations of 0.6 and 2 mg/mL, and omeprazole-sodium bicarbonate 40-mg packets were suspended to initial omeprazole concentrations of 1.2, 2, 3, and 4 mg/mL. Suspensions were stored at 4 degrees C in darkness (refrigerated) or 22-25 degrees C (room temperature) in light for one week. A third set of suspensions was stored refrigerated for one month. Omeprazole's stability was quantified after 0, 6, 12, 24, 48, and 168 hours in one-week samples and after 0, 7, 14, 21, and 28 days in one-month samples using high-pressure liquid chromatography. Viscosities of refrigerated suspensions were measured after 0, 1, and 7 days. RESULTS: Refrigerated suspensions retained >98% and >96% of their initial omeprazole concentrations after one week and one month, respectively. Stability of room temperature suspensions was concentration dependent. After one week, the 0.6- and 1.2-mg/mL suspensions retained 87.2% and 93.1% of their respective initial omeprazole concentrations, whereas the 2-, 3-, and 4-mg/mL suspensions retained >97% of their initial omeprazole concentrations. Suspension viscosities varied 10-fold over the concentrations studied, but all were within the viscosity ranges of other commercially available oral suspensions. Prolonged refrigeration did not increase the suspensions' viscosities. CONCLUSION: Omeprazole-sodium bicarbonate suspensions of 0.6-4 mg/mL omeprazole were stored at 4 degrees C in darkness for up to 28 days. The viscosities of refrigerated suspensions did not increase over 7 days. Except for the 0.6 mg/mL preparations, suspensions stored at room temperature in the light retained >90% of their initial omeprazole content after 7 days, despite turning yellow.     

Stability of vecuronium in sterile water for injection stored in polypropylene syringes for 21 days.

PURPOSE: The stability of vecuronium bromide 1 mg/mL in preservative-free sterile water for injection for up to 21 days was studied. METHODS: A vecuronium bromide 1-mg/mL solution was prepared by diluting 15 vials of 10-mg Vecuronium Bromide for Injection, USP, powder with preservative-free sterile water for injection and adding the solution to an evacuated i.v. bag. Identical 10-mL volumes of the solution were prepared and stored at 23-25 or 3-5 degrees C in polypropylene syringes. The stability of vecuronium was analyzed in triplicate with stability-indicating high-performance liquid chromatography immediately after preparation of solutions and at 3, 7, 14, and 21 days. The samples were also inspected for volume and color change and for visible precipitation and microbial growth. RESULTS: The percentage of the initial vecuronium bromide concentration remaining at each time point was greater than 100% at both 23-25 and 3-5 degrees C. There were no detectable changes in volume or color and no precipitation or visible microbial growth. CONCLUSION: Vecuronium bromide in an extemporaneously prepared solution in preservative-free sterile water for injection was stable for at least 21 days at 23-25 or 3-5 degrees C.