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.     

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 valacyclovir hydrochloride in extemporaneously prepared oral liquids.

The stability of valacyclovir hydrochloride in three commonly used syrups was studied. Triplicate suspensions of valacyclovir (from caplets) in Ora-Sweet (Paddock Laboratories), Ora-Sweet SF (Paddock), and Syrpalta Humco Laboratory) syrups were extemporaneously compounded to yield a final concentration of valacyclovir 50 mg/mL (as the hydrochloride salt). The nine suspensions were stored at 4 degrees C in amber glass bottles. At intervals up to 60 days, the liquids were visually inspected for color change, cloudiness, gas formation, and precipitation, and samples were assayed in duplicate for valacyclovir concentration by stability-indicating high-performance liquid chromatography. Also tested were pH, particle size, and microbial growth. During the first 21 days of storage, mean valacyclovir concentrations in all liquids were >90% of the initial concentration, but concentrations were <90% by day 21 in some individual samples of suspensions prepared with Ora-Sweet and Ora-Sweet SF. Mean valacyclovir concentrations in the Syrpalta-based suspensions met the 90% cutoff for at least 35 days. Solution pH and particle size remained unchanged in all liquids through day 60, and there were no changes in physical appearance. There was no evidence of microbial growth on the days when microbial growth was tested (0 and 28). Valacyclovir 50 mg/mL (as the hydrochloride salt) in three oral liquids stored in amber glass bottles at 4 degrees C was stable for at least 21 days when prepared with two of three syrups and for at least 35 days when prepared with the third syrup. All the liquids were free of microbial growth for at least 28 days.     

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.     

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.     

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 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 fumagillin in an extemporaneously prepared ophthalmic solution.

The stability of fumagillin 70 microg/mL (as the bicyclohexylammonium crystal) in an extemporaneously prepared ophthalmic solution was studied. An ophthalmic solution of fumagillin 70 microg/mL was prepared by combining 120 mg of fumagillin bicyclohexylammonium crystals with 20 mL of 0.9% Sodium Chloride Injection, USP, and 20 mL of an ophthalmic irrigating solution. The solution was stored in 12 sterile semi-opaque dropper bottles; 4 bottles were stored at 25 degrees C exposed to light, 4 were stored at 25 degrees C in the dark, and 4 were stored at 4 degrees C in the dark. Samples were taken on days 0, 7, 14, 21, and 28 and analyzed by high-performance liquid chromatography. Sterility was tested as well. In the solutions stored at 25 degrees C, 17-30% of the initial drug concentration was lost during the first week. The solution protected from light and stored at 4 degrees C lost about 12% of active drug by week 4. There was no change in color or odor in any of the solutions and only a minor change in pH over the study period. There was no evidence of microbial growth in any of the solutions tested. Fumagillin 70 microg/mL (as the bicyclohexylammonium crystal) in 0.9% sodium chloride injection and an ophthalmic irrigating solution containing benzalkonium chloride was stable in the dark for 14 days at 4 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 allopurinol and of five antineoplastics in suspension

The stability of allopurinol, azathioprine, chlorambucil, melphalan, mercaptopurine, and thioguanine each in an extemporaneously prepared suspension was studied. Tablets of each drug were crushed, mixed with a suspending agent, and brought to a final volume of 10, 15, or 20 ml with a 2:1 mixture of simple syrup and wild cherry syrup. Suspensions were prepared in the following concentrations: allopurinol (20 mg/ml), azathioprine (50 mg/ml), chlorambucil (2 mg/ml), melphalan (2 mg/ml), mercaptopurine (50 mg/ml), and thioguanine (40 mg/ml). Using high-performance liquid chromatography or ultraviolet scans, duplicate assays were performed on each suspension periodically during storage for up to 84 days at ambient room temperature or 5 degrees C. The time required for the suspensions to drop below 90% of labeled strength was used as an indicator of drug stability. Allopurinol and azathioprine were stable for at least 56 days at room temperature and at 5 degrees C. Chlorambucil decomposed rapidly at room temperature but was stable for seven days when stored at 5 degrees C. Melphalan suspensions did not meet the stated criteria for stability even at the time of initial assay. Mercaptopurine and thioguanine were stable for 14 and 84 days, respectively, at room temperature; at 5 degrees C, assay values dropped below those obtained at room temperature. In the suspension formulation tested, allopurinol, azathioprine, mercaptopurine, and thioguanine are stable for at least 14 days at room temperature; chlorambucil suspensions should be refrigerated and discarded after seven days. Melphalan decomposes too rapidly to make this suspension formulation feasible for extemporaneous compounding.     

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.