Stability of dapsone in two oral liquid dosage forms.

OBJECTIVE: Dapsone use in pediatric patients is increasing; however, the currently available tablet dosage form cannot be used in young children. The objective of our study was to determine the stability of dapsone in two oral suspensions stored at two temperatures. METHODS: Commercially available dapsone tablets (25 mg) were used to prepare the suspensions: the first in simple syrup and water with citric acid, the second in 1:1 Ora Sweet:Ora Plus to yield a concentration of 2.0 mg/mL. The dosage forms were stored in 10 amber plastic prescription bottles. Five were stored at 25 degrees C and five at 4 degrees C. Three samples were taken from each of five bottles at 0, 7, 14, 28, 42, 56, 70, and 91 days (n = 15). Dapsone concentrations in each sample were measured in duplicate by a validated and stability-indicating HPLC method; the pH of each sample was also determined. The drug was considered stable if the mean concentration > or =90% of the original concentration. RESULTS: The mean concentrations of dapsone were >95% of the initial concentrations for 91 days at both 4 degrees C and 25 degrees C in each suspension. There was a slight darkening of the samples stored at 25 degrees C. CONCLUSIONS: Dapsone was stable in two suspensions prepared from commercially available tablets for at least three months at 4 degrees C and 25 degrees C.

Stability of propylthiouracil in extemporaneously prepared oral suspensions at 4 and 25 degrees C.

The stability of propylthiouracil in two extemporaneously prepared suspensions at 4 and 25 degrees C was studied. Commercially available 50-mg propylthiouracil tablets were used to prepare suspensions in 1:1 Ora-Sweet:Ora-Plus and in 1:1 1% methylcellulose:Simple Syrup, NF, to yield a propylthiouracil concentration of 5 mg/mL. Each suspension was stored in 10 amber plastic prescription bottles, 5 of them at 4 degrees C and the other 5 at 25 degrees C. Three samples were taken from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days for assay by stability-indicating high-performance liquid chromatography. More than 90% of the initial propylthiouracil concentration was retained in both suspensions for 70 days at 25 degrees C and for 91 days at 4 degrees C. There were no changes in physical appearance, color, or odor, and the pH remained essentially unchanged. Propylthiouracil 5 mg/mL in two extemporaneously prepared oral suspensions was stable for at least 70 days at 25 degrees C and for at least 91 days at 4 degrees C.

Development of two stable oral suspensions of levodopa-carbidopa for children with amblyopia.

PURPOSE: To develop stable liquid dosage forms of levodopa-carbidopa for use in children with amblyopia. METHODS: Levodopa (100 mg) and carbidopa (25 mg) tablets were used to prepare the suspensions at 5 and 1.25 mg/mL, respectively. For each suspension, five bottles were stored at 25 degrees C and five at 4 degrees C. Three samples were taken from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days (n=15). Levodopa-carbidopa concentrations for each sample were measured in duplicate by validated and stability-indicating high-performance liquid chromatographic method. RESULTS: The mean concentrations of levodopa-carbidopa in Ora Plus/Ora Sweet suspensions were 96% and 92% of the initial concentrations for 28 days at 25 degrees C, and 94% and 93% for 42 days at 4 degrees C. In the suspension containing ascorbic acid, the mean concentrations of levodopa-carbidopa were above 93% and 92% for 14 days at 25 degrees C, and 93% and 92% for 28 days at 4 degrees C. This liquid formulation was administered to 15 children (mean age: 5.6+/-1.4 years) with amblyopia. The number and type of adverse effects were similar in the levo-dopa-carbidopa versus placebo group. CONCLUSION: Levodopa-carbidopa in extemporaneous suspensions prepared in Ora Plus and Ora Sweet were stable for 28 days when stored at 25 degrees C and for 42 days at 4 degrees C. Our data suggest our liquid formulation may be used safely in children with amblyopia.

Stability of amlodipine besylate in two liquid dosage forms.

OBJECTIVE: To determine the stability of amlodipine besylate in two liquid dosage forms under refrigeration and at room temperature. DESIGN: Commercially available amlodipine tablets (Norvasc-Pfizer) were used to prepare two suspensions: one in extemporaneously prepared 1% methylcellulose in syrup (1:1), and another in equal volumes of commercially available OraPlus/OraSweet. Each suspension containing amlodipine 1 mg/mL was stored in 10 plastic prescription bottles; 5 were stored at 4 degrees C and 5 at 25 degrees C. Samples were collected immediately after preparation (day 0) and on days 7, 14, 28, 42, 56, 70, and 91. Amlodipine concentration was measured by stability-indicating HPLC method (n = 15). SETTING: Research laboratory at Children's Hospital. MAIN OUTCOME MEASURES: Physical and chemical stability (> 90% of the initial concentration) of amlodipine in the two extemporaneously prepared suspensions during storage in plastic prescription bottles at 4 degrees C and 25 degrees C. RESULTS: Observed mean concentrations exceeded 90% of the initial concentrations in both suspensions for 91 days at 4 degrees C and 56 days at 25 degrees C. No noticeable change in physical appearance or odor was observed; pH changed slightly in the methylcellulose-containing formulation stored at 25 degrees C. CONCLUSION: Amlodipine was stable in two suspensions when stored in plastic prescription bottles for 91 days at 4 degrees C or 56 days at 25 degrees C. These formulations may be considered for pediatric or elderly patients who are unable to swallow tablets. The liquid dosage form would also permit accurate administration of amlodipine doses to infants and young children based on their body weight.

Stability of lamotrigine in two extemporaneously prepared oral suspensions at 4 and 25 degrees C.

The stability of lamotrigine 1 mg/mL in two extemporaneously prepared oral suspensions at 4 and 25 degrees C was studied. Lamotrigine tablets 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 Ora-Sweet SF and Ora-Plus (Paddock Laboratories) to produce two 1-mg/mL suspensions. One 100-mg lamotrigine tablet was used to prepare one 100-mL batch of each suspension. The suspensions were stored in amber polyethylene terephthalate 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 lamotrigine content by high-performance liquid chromatography; pH was measured, and the samples were visually observed against a black and white background. The mean concentration of lamotrigine was >99% of the initial concentration in all samples throughout the 91-day study period; there was no change in apparent pH, odor, or physical appearance. Lamotrigine 1 mg/mL in two extemporaneously compounded oral suspensions was stable for 91 days in polyethylene terephthalate prescription bottles at 4 and 25 degrees C.

Stability of enalapril maleate in three extemporaneously prepared oral liquids.

The stability of enalapril 1 mg/mL (as the maleate) in deionized water, citrate buffer solution, and a sweetened suspending agent at two temperatures was studied. Twenty enalapril 10-mg tablets were crushed to a powder. Deionized water, citrate buffer solution, or sweetened vehicle was added to produce three 200-mL batches of each liquid; the expected final concentration of enalapril in each was 1 mg/mL. Each formulation was stored in 10 60-mL bottles, 5 of which were stored at 4 degrees C and 5 at 25 degrees C. Samples were collected on days 0, 7, 14, 28, 42, 56, 70, and 91 for visual inspection and analysis by high-performance liquid chromatography; pH was measured at each sampling time as well. The mean concentration of enalapril in the three liquids at 4 degrees C was > 94% of the initial concentration throughout the 91-day study period. At 25 degrees C, the mean concentration of enalapril was > 90% for 56 days and > 92% for 91 days in both citrate buffer solution and sweetened vehicle. The pH of the liquid prepared with deionized water and stored at 25 degrees C decreased by 2.0 pH units. Enalapril 1 mg/mL (as the maleate) in three extemporaneously compounded oral liquids was stable for 91 days at 4 and 25 degrees C with the exception of enalapril in deionized water, which was stable for only 56 days at 25 degrees C.

Stability of pyrimethamine in a liquid dosage formulation stored for three months.

The stability of pyrimethamine in a liquid dosage formulation stored for up to three months was studies. Commercially available 25-mg pyrimethamine tablets were crushed with a mortar and pestle and mixed with a 1:1 mixture of Simple Syrup, NF, and 1% methylcellulose to yield a suspension with a pyrimethamine concentration of 2 mg/mL. The suspension was poured into 10 amber plastic and 10 amber glass prescription bottles; 5 plastic and 5 glass bottles were stored at 4 degrees C, and the remaining bottles were kept at 25 degrees C. Samples were collected at intervals up to 91 days and tested for pyrimethamine concentration by stability-indicating high-performance liquid chromatography. Pyrimethamine remained stable throughout the three-month study period under all conditions. At 4 degrees C, pyrimethamine concentrations remained above 96% of the initial concentration; at 25 degrees C, pyrimethamine concentrations remained above 91%. No substantial changes in pH were observed. Pyrimethamine was stable for at least 91 days in an oral suspension stored in plastic or glass prescription bottles at 4 or 25 degrees C.

Stability and compatibility of anakinra with ceftriaxone sodium injection in 0.9% sodium chloride or 5% dextrose injection.

The stability and compatibility of anakinra (recombinant human interleukin-1 receptor antagonist) with ceftriaxone sodium in 0.9% sodium chloride or 5% dextrose injection was determined during a 4-h period at ambient room temperature and light. Anakinra was diluted in 0.9% sodium chloride or 5% dextrose to the concentrations of 4 and 36 mg/ml. Anakinra, at each concentration was mixed with ceftriaxone sodium (20 mg/ml) in a 50:50 proportion and stored in plastic culture vials with polypropylene caps. The samples were collected at 0, 2 and 4 h after mixing. Anakinra and ceftriaxone concentrations were measured using stability-indicating HPLC methods. In 0.9% sodium chloride injection, the mean concentrations of anakinra and ceftriaxone exceeded 98% of initial concentrations at the end of the study period. In 5% dextrose, however, anakinra concentrations were below 90% of the expected initial concentration at the time of first analysis (within 0.5 h). Thus, anakinra appears to be stable and compatible with ceftriaxone sodium when diluted in 0.9% sodium chloride injection, but not in 5% dextrose injection over 4 h at ambient room temperature and light.

Stability and compatibility of anakinra with intravenous cimetidine hydrochloride or famotidine in 0.9% sodium chloride injection.

We designed a study to evaluate the stability and compatibility of anakinra (recombinant human interleukin-1 receptor antagonist) with cimetidine hydrochloride or famotidine in 0.9% sodium chloride injection during a 4-h period at room temperature (22 degrees C) and light. Anakinra was diluted in 0.9% sodium chloride to concentrations of 4 and 36 mg/ml. At each concentration, anakinra was mixed with 3 mg/ml cimetidine or with 1 mg/ml famotidine, in a 50:50 proportion and stored in plastic culture vials with polypropylene caps. The mean concentrations of anakinra, cimetidine hydrochloride, and famotidine exceeded 95% of initial concentrations throughout the study. No changes were noted in the physical appearance, pH, or the chromatograms during the study period. Thus, anakinra appears to be stable and compatible with cimetidine hydrochloride or famotidine when diluted into 0.9% sodium chloride injection for 4 h at ambient room temperature and light.

Stability of cisapride in a liquid dosage form at two temperatures.

OBJECTIVE: To determine the stability of cisapride in a liquid dosage form stored in plastic bottles at 2 temperatures. DESIGN: Cisapride tablets were used to prepare a suspension in equal volumes of methylcellulose 1% and simple syrup to yield a concentration of 1 mg/mL. The cisapride suspension was stored in 10 amber plastic prescription bottles. Five bottles were stored at room temperature (25 +/- 0.1 degrees C) and 5 under refrigeration (4 degrees C). Samples were drawn from each bottle immediately after mixing (day 0), and at 7, 14, 28, 42, 56, 70, and 91 days of storage at each temperature. All samples were analyzed in duplicate on each day of analysis. Cisapride was measured by a stability-indicating HPLC method. RESULTS: The mean concentration of cisapride exceeded 90% of its initial concentration throughout the 91-day study period at 4 degrees C, but only during the first 28 days at 25 degrees C. No significant change in pH was observed during the study period. CONCLUSIONS: Cisapride was stable in a suspension for 91 days at 4 degrees C and 28 days at 25 degrees C in amber plastic prescription bottles.

Stability of rifampin in two suspensions at room temperature.

The objective of our study was to determine the stability of rifampin (rifampcin) in two extemporaneously prepared suspensions at room temperature. Two suspensions were prepared in syrup by using intravenous rifampin (A) or rifampin capsules (B). Each suspension was stored in five plastic prescription bottles. During the first week, the mean measured concentrations of rifampin were nearly 100% of initial concentration in suspension A, but were 77-83% of the expected (labelled) concentration in suspension B. The maximum concentrations of rifampin were observed immediately after preparation of suspension A, but not until 14 days in suspension B. On day 56, the mean concentration of rifampin was about 95% of initial concentration in suspension A, and close to 90% of the labelled potency (10 mg/ml) in suspension B. Rifampin was found to be chemically stable in each suspension for 56 days at room temperature. Suspensions prepared from the capsules may be non-homogeneous and lead to unsatisfactory dosing.

Effect of preparation method and storage on rifampin concentration in suspensions.

OBJECTIVE: To determine the effect of four preparation methods and extended storage on rifampin concentration in extemporaneously prepared suspensions. DESIGN: Four preparation methods were used: mixing intravenous (i.v.) rifampin in syrup (A); manufacturer's recommended technique of mixing capsule (Rifadin) contents in syrup (B); triturating capsule contents in syrup into a paste and adding remaining syrup while mixing (C); and triturating capsule contents in syrup into a paste, adding syrup, retriturating the slurry, and adding remaining syrup while mixing (D). Samples were drawn from each of five bottles of each of the four preparations stored at 4 degrees C, immediately after mixing (day 0), and on days 7, 14, 28, 42, 56, 70, and 91 days during storage. Rifampin was measured by a stability-indicating HPLC method. RESULTS: The measured mean concentrations of rifampin were nearly 100 percent of the initial concentration in the suspension prepared from i.v. rifampin solution (method A) during the first 56 days of storage. In contrast, the measured concentrations were substantially lower than expected in the suspensions prepared by methods B, C, and D. The mean rifampin concentrations in suspensions prepared by methods B, C, and D were only 14.5, 38.6, and 68 percent, respectively, of the initial concentration achieved by method A. The rifampin concentrations increased with storage time in suspensions prepared by methods B, C, and D. The mean rifampin concentration was lower than 90 percent during the first 14 days with methods B and C, and the first 7 days with method D. The highest mean concentrations were observed on day 42 with method B, and on day 28 with methods C and D. All methods yielded 90% of the labeled potency (10 mg/mL) on day 56. CONCLUSIONS: Our results showed that preparation method can influence the dispersion, and thus the measured concentration, of rifampin in aliquots of suspensions prepared from capsules and stored in plastic bottles. Suspensions prepared from capsules led to lower-than-expected rifampin concentrations; those prepared from i.v. rifampin did not. Rifampin was stable in each type of suspension for 56 days at 4 degrees C.