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 A 1-mL sample was withdrawn from each of the 12 bottles immediately and after 7, 14, 30, 60, and 90 days.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 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 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 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 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 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 1% rifampin suspensions prepared in five syrups

The stability and microbiological activity (potency) of rifampin in 1% w/v suspensions prepared extemporaneously using five syrups was studied. The contents of four 300-mg rifampin capsules (Rifadin, Merrell Dow Pharmaceuticals Inc.) were crushed and placed in amber glass bottles. The rifampin powder was combined with 120 mL of each of the following syrups: Syrup, NF; two commercially available simple syrups (Humco Laboratories and Whiteworth, Inc.), wild cherry syrup (Eli Lilly and Company), and a fruit-flavored syrup (Syrpalta). The bottles were then stored at room temperature or under refrigeration for six weeks. Portions of each suspension were removed and assayed using high-performance liquid chromatography (HPLC) and a microbiological assay technique initially and after two, four, and six weeks of storage. No significant changes in rifampin concentrations were detected by either assay technique over the study period. However, an increase in the concentration of rifampin degradation products was detected by HPLC assay, especially between the fourth and sixth weeks. A 1% w/v suspension of rifampin prepared using Rifadin capsules and any of the five syrups studied is stable for four weeks at room temperature or under refrigeration.     

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 ranitidine syrup re-packaged in unit-dose containers.

PURPOSE: The stability of ranitidine syrup re-packaged in unit-dose containers was studied. METHODS: Oral ranitidine hydrochloride syrup containing 16.8 mg/mL of ranitidine hydrochloride (equivalent to 15 mg of ranitidine) in original bulk containers and re-packaged in unit-dose amber-colored glass bottles sealed with aluminum caps were obtained from commercial sources. For extended-stability determinations, samples were stored for 52 weeks at 25 degrees C and 40% relative humidity and analyzed at 0, 4, 13, 26, 39, and 52 weeks. For accelerated stability determinations, samples were stored for 13 weeks at 40 degrees C and 25% relative humidity and analyzed at 0, 4, 9, and 13 weeks. Stability was assessed using high-performance liquid chromatography and by measuring changes in pH and sample weight. The principal impurity and total impurities were also measured. RESULTS: No significant changes in pH were demonstrated, and all values remained well within acceptable limits. The weight change in samples was greater for re-packaged samples stored in accelerated conditions compared with that of samples in the original packaging; however, the differences were not significant. Ranitidine hydrochloride samples in both types of packaging remained stable when stored at 25 degrees C and 40% relative humidity for 52 weeks and at 40 degrees C and 25% relative humidity for 13 weeks. The impurity profiles remained within acceptable limits for all samples. CONCLUSION: Re-packaged ranitidine syrup was stable for up to 52 weeks when stored at 25 degrees C and 40% relative humidity and for up to 13 weeks when stored at 40 degrees C and 25% relative humidity.     

Stability of procainamide hydrochloride in an extemporaneously compounded oral liquid.

The stability of procainamide hydrochloride 5, 50, and 100 mg/mL in an extemporaneous oral liquid formulation was studied. Oral liquids containing procainamide hydrochloride 5, 50, or 100 mg/mL were compounded from procainamide hydrochloride capsules, sterile water for irrigation, and cherry syrup or a 70:30 mixture of 1% methylcellulose and cherry syrup. The pH values of the liquids were 6 (unadjusted) and 5 (adjusted). The liquids were stored at 4-6 degrees C or 24-25 degrees C and tested for drug concentration by stability-indicating high-performance liquid chromatography at 0, 7, 14, 21, 28, 34, 147, and 180 days. The relationships among the variables drug concentration, type of vehicle, pH, and temperature and their effects on drug stability were analyzed by using repeated-measures analysis of variance. With respect to effects on stability across time, there was a significant three-way interaction among drug concentration, type of vehicle, and temperature. The effect of concentration on stability seemed to depend on the vehicle used, but this dependence was different for different temperatures and different pH values. When trends over time were considered, a significant interaction among time, vehicle type, and temperature was found. This reflected the stability of the concentration of procainamide hydrochloride over time under refrigeration for both vehicles, compared with the steady decline in drug concentration at room temperature. Overall, drug concentration was fairly stable over time in the 5- and 50-mg/mL oral liquids but declined steadily in the 100-mg/mL liquid.(ABSTRACT TRUNCATED AT 250 WORDS)