Stability of cephalexin monohydrate suspension in polypropylene oral syringes

The stability of cephalexin monohydrate suspension in plastic oral syringes was studied. Commercially available cephalexin monohydrate powder for oral administration was reconstituted according to the manufacturer's instructions and stored in the original containers or drawn into 5-mL clear polypropylene oral syringes. The original containers and syringes were divided into groups and stored at -20, 4, 25, 40, 60, or 80 degrees C. Powder from two additional lots was similarly reconstituted and packaged; these original containers and syringes were stored at 80 degrees C only to assess interlot variability. Immediately after reconstitution and at specified times during storage, three syringes and the corresponding three original containers stored at each temperature were removed, and their contents were analyzed for cephalexin concentration using the standard USP iodometric assay for antibiotics. The stability-indicating nature of the assay was documented. Cephalexin monohydrate followed a first-order rate of degradation at temperatures of 40, 60, and 80 degrees C. At temperatures of -20, 4, and 25 degrees C, cephalexin monohydrate exhibited no appreciable degradation during the 90-day study period. Cephalexin monohydrate suspension reconstituted from powder as a suspension and repackaged in clear polypropylene oral syringes was stable for 90 days when stored under ambient, refrigerated, and frozen conditions.     

Stability of oral liquid penicillins in unit dose containers at various temperatures.

The effect of freezing on the stability of reconstituted, unit dose packaged oral amoxicillin trihydrate and ampicillin suspensions and penicillin V potassium solutions was studied. Powders for suspension or solution of the three penicillins were reconstituted according to manufacturers' directions to yield a concentration of 250 mg/5 ml. Samples of 5 ml then were stored in amber, screw-cap, glass vials at 25 C, 5 C, 0 C, -10 C or -20 C for 5, 10, 20, 30 or 60 days. The concentration of active constituents remaining after storage was determined spectrophotometrically. All three penicillins retained at least 90% of their original activity for at least 60 days when stored at -20 C. Ampicillin and pencillin V potassium retained at least 90% of their activity after 60 days of storage at -10 C but amoxicillin concentration decreased to 88% and 87% of initial concentration after 60 days storage at -10 C and 0 C, respectively. Degradation appeared to be by a zero-order process for amoxicillin and ampicillin and by a first-order process for penicillin V potassium. It appears that oral solutions of amoxicillin, ampicillin and penicillin V potassium can be effectively stored for at least 50 days in a freezer at -10 C with little loss of activity.     

Stability of dicloxacillin sodium oral suspension stored in polypropylene syringes

The stability of dicloxacillin sodium in oral suspension stored in clear polypropylene oral syringes was studied. Commercially available dicloxacillin sodium powder for oral suspension from a single lot was reconstituted according to the manufacturer's instructions and drawn into 5-mL clear polypropylene oral syringes. The syringes were divided into groups and stored at -20, 4, 25, 40, 60 or 80 degrees C. Two additional lots were similarly reconstituted, repackaged, and stored at 80 degrees C only to assess interlot variability. Powder in the original containers was similarly reconstituted according to the manufacturer's instructions, and the containers were divided into groups and stored with the syringes. Immediately after reconstitution and at specified times during storage, three syringes and the original containers at each storage temperature were removed, and their contents were analyzed for dicloxacillin sodium concentration using the Standard USP Iodometric Assay. Dicloxacillin sodium follows a first-order rate of degradation at temperatures of 40, 60, and 80 degrees C. The rate of degradation changes to a zero-order process at temperatures of 25, 4, and -20 degrees C. At all temperatures, degradation occurred more rapidly when the drug was repackaged into unit dose polypropylene oral syringes than in the manufacturer's original container. Dicloxacillin sodium reconstituted from powder as oral suspension and repackaged in clear polypropylene syringes was stable for no longer than 7, 10, and 21 days when stored under ambient, refrigerated, and frozen conditions, respectively.     

Stability of nifedipine in an extemporaneously compounded oral solution.

The stability of nifedipine in an extemporaneously compounded oral solution is described. A solution of nifedipine 10 mg/mL was prepared from commercially available nifedipine powder with polyethylene glycol 400, glycerin, and peppermint oil. Four samples were stored in amber glass bottles at room temperature under fluorescent lighting and analyzed in duplicate. Samples were analyzed immediately and at 7, 14, 23, and 35 days. Eight samples were stored in amber oral syringes and eight in amber oral syringes wrapped in aluminum foil; all were stored at room temperature under fluorescent lighting. Samples from foil-wrapped syringes were analyzed at 7 and 14 days; samples not wrapped in foil were analyzed after 7 days. Nifedipine concentrations were measured with a modified stability-indicating high-performance liquid chromatographic method. Excessive degradation was defined as a greater than 10% loss of initial drug concentration. There were no detectable changes in color or odor and no visible solids or microbial growth was observed in any sample. Samples in amber glass bottles and amber oral syringes wrapped in aluminum foil retained more than 90% of the initial nifedipine for 35 and 14 days, respectively. Samples packaged in amber oral syringes not wrapped in foil lost over 20% of the initial nifedipine concentration within 7 days. Nifedipine 10 mg/mL was stable in an oral solution prepared from commercially available powder in a peppermint-flavored vehicle for at least 35 days when stored at 22-25 degrees C in amber glass bottles and for at least 14 days when stored in amber oral syringes wrapped in aluminum foil.     

Stability of penicillin V potassium in unit dose oral syringes.

The stability of reconstituted penicillin V potassium (PVK) when stored in 6-ml plastic oral syringes at various temperatures and protected from light was studied. One batch of PVK was reconstituted with distilled water according to manufacturer's directions (label claim: 125 mg/ml). Samples of 5 ml were stored in plastic oral syringes at 4 C, 25 C, 41 C, 60 C or 75 C and assayed spectrophotometrically and microbiogically at various times. From an initial concentration of 113% of label claim, PVK stored at 4 C (refrigerated) reached 90% of manufacturer's label claim in 11.5 days (95% confidence level). PVK stored at 25 C (room temperature) was unstable after storage for less than 37 hours. PVK degradation followed a first-order process. No significant difference was found between the spectrophotometric and microbiological assay (p less than 0.05). Manufacturer's stability data for storage of reconstituted PVK in the original bulk container should not be applied to PVK repackaged in plastic oral syringes. The pharmacy department developed guideliness designed to prevent the administration of subpotent PVK.     

Stability of amoxicillin trihydrate-potassium clavulanate in original containers and unit dose oral syringes

The stability of reconstituted amoxicillin trihydrate-potassium clavulanate oral suspension both in original containers and pre-packaged in commercially available oral syringes stored at various temperatures was determined. Amoxicillin trihydrate 125 mg/5 mL-potassium clavulanate 31.25 mg/5 mL and amoxicillin trihydrate 250 mg/5 mL-potassium clavulanate 62.5 mg/5 mL were reconstituted according to the manufacturer's instructions. The reconstituted suspensions in the original containers and in five brands of oral syringes were stored at 5 degrees C and 25 degrees C and -10 degrees C, 5 degrees C, and 25 degrees C, respectively, for 0, 2, 4, 7, and 14 days. The concentrations of amoxicillin trihydrate and potassium clavulanate remaining after storage were assayed in triplicate by reverse-phase high-performance liquid chromatography, using a stability-indicating method. An F statistic was calculated to determine whether different syringe brands had significantly different effects on drug stability. Amoxicillin trihydrate was stable for at least 10 days in the original containers and all types of oral syringes at 5 degrees C. However, potassium clavulanate was stable for 11.1 days in original containers and less than 5 days in all types of oral syringes at 5 degrees C. The effect of syringe brand on the stability of drugs over time at specific storage conditions and temperature was significant for potassium clavulanate at 5 degrees C and for both amoxicillin trihydrate and potassium clavulanate at 25 degrees C. The manufacturer's guidelines for storage of reconstituted amoxicillin trihydrate-potassium clavulanate oral suspension in the original containers should not be applied to dosages repackaged in unit dose oral syringes.     

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 acetazolamide in suspension compounded from tablets

The stability of acetazolamide in an extemporaneous suspension compounded from tablets was studied. Acetazolamide 25-mg/mL suspension was prepared by levigating the comminuted 250-mg tablets with 70% sorbitol solution. The mixture was incorporated into a suspension vehicle containing magnesium aluminum silicate and carboxymethylcellulose sodium. Appropriate sweeteners, flavoring agents, preservatives, humectants, and pH adjusters were then added. The suspension was stored in amber glass bottles at 5, 22, 30, 40, and 50 degrees C. Samples were analyzed for the concentration of acetazolamide by stability-indicating high-performance liquid chromatography on days 3, 7, 11, 18, 24, 32, 42, 54, and 79. For batches stored at 5, 22, and 30 degrees C, the initial acetazolamide concentration was maintained during the entire 79 days of the study. However, the concentrations in the batches stored at 40 and 50 degrees C were below 90% of the initial value after 79 and 32 days, respectively. The Arrhenius plot was used to predict a shelf life of the suspension at room temperature of 371 days. Acetazolamide oral suspension 25 mg/mL was stable for at least 79 days at 5, 22, and 30 degrees C. The formulation should be maintained at pH 4-5 and stored in amber glass bottles.     

Stability of propranolol hydrochloride suspension compounded from tablets

The stability of a propranolol hydrochloride suspension compounded from commercially available tablets was studied. Propranolol hydrochloride 10-mg tablets were triturated to a powder and incorporated into a commercially available suspension vehicle to yield a suspension with a theoretical propranolol hydrochloride concentration of 1 mg/mL. The suspension was divided into portions and stored in amber glass bottles at either room (25 degrees C) or refrigerated (2 degrees C) temperature for four months. The concentration of propranolol hydrochloride in the samples was determined by a stability-indicating, high-performance liquid chromatographic (HPLC) assay at 0, 30, 60, 90, and 120 days. Also at these times, the pH of the samples was measured, and the samples were inspected visually for evidence of microbial growth and ease of resuspension. The concentration of propranolol hydrochloride in the samples remained within 90% of the initial concentration throughout the study period. No important changes in the pH of the samples and no visible evidence of microbial growth were noted. This extemporaneous suspension of propranolol hydrochloride compounded from commercially available tablets is stable for at least four months when stored at room or refrigerated temperature.     

Formulation and stability of diazepam suspension compounded from tablets

The stability of diazepam in an extemporaneous suspension compounded from tablets was studied. A diazepam 1 mg/mL suspension was prepared by levigating diazepam 10-mg tablets with ethanol and propylene glycol and incorporating them into a suspension vehicle containing magnesium aluminum silicate and carboxymethylcellulose sodium with flavoring and sweetening agents. Samples of the suspension were stored in amber glass bottles at 5, 22, and 40 degrees C. At various times during the 60-day study period, samples were inspected visually for signs of caking or color change and evaluated for ease of pouring and redispersion. Also at those times, the concentration of diazepam in each sample was determined by a stability-indicating, high-performance liquid chromatography procedure. The concentration of diazepam in each sample was at least 90% of the initial concentration throughout the 60-day storage period. All samples remained homogeneous and showed no signs of caking or settling. A diazepam suspension compounded from tablets was found to be pharmaceutically acceptable and easily pourable and redispersible. The suspension is stable for at least 60 days at room or refrigerated 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.     

Urokinase activity after freezing: implications for thrombolysis in intraventricular hemorrhage.

The retention of urokinase activity after frozen storage was studied. Urokinase powder was reconstituted aseptically in sterile water for injection or preservative-free 0.9% sodium chloride injection to a final concentration of 5000 IU/mL. Samples were stored in 5-mL plastic syringes at -20 or -70 degrees C for up to six months. Samples containing urokinase 25,000 IU/mL were similarly prepared by using sodium chloride injection as the diluent and were stored frozen at the same temperatures for up to 93 days. Urokinase activity was measured with a chromogenic assay at each test interval. Samples were also cultured after thawing to evaluate their potential to support microbial growth. The activity of urokinase at either concentration did not change appreciably during the study period. The method of thawing-at room temperature or in a refrigerator-had no effect on urokinase activity. No microbial growth was observed. Urokinase 5000 IU/mL did not show any changes in activity when reconstituted with sterile water for injection or 0.9% sodium chloride injection and frozen for up to six months. Urokinase 25,000 IU/mL in sodium chloride injection was also stable after 93 days of frozen storage.     

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 and availability of cyclosporine stored in plastic syringes

The stability and availability of cyclosporine from the oral dosage form when stored in plastic syringes were examined. Solutions of cyclosporine were stored in plastic syringes for 28 days at 25 degrees C. Half of the solutions remained in room light, and samples were obtained at 3, 6, and 12 hours and 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 days. The remaining samples were protected from light, and samples were obtained at 1, 3, 5, 7, 14, 21, and 28 days. Samples stored in plastic were compared with control solutions stored in the original amber bottle. All samples were analyzed for unchanged cyclosporine by high-pressure liquid chromatography. Cyclosporine was stable and completely available from the oral dosage form when stored in plastic syringes for up to 28 days. There was no difference in the stability of cyclosporine between the solutions exposed to room light and those protected from light. Solutions of the oral dosage form of cyclosporine may be stored in plastic syringes without protection from light for up to 28 days.     

Stability of carbamazepine suspension after repackaging into four types of single-dose containers

The stability of carbamazepine in commercially available suspension that had been repackaged in various single-dose containers was studied. Carbamazepine suspension was repackaged in 2-mL and 8-mL aliquots in amber glass vials, polypropylene vials, and amber polypropylene syringes and in 2-mL aliquots in amber glass oral syringes. Containers were stored at room temperature and continuously exposed to fluorescent light for up to 12 weeks. Samples from each container type and volume were assayed for carbamazepine content by high-performance liquid chromatography at various intervals during storage. Carbamazepine concentrations in the samples were compared with the carbamazepine concentration in the original manufacturer's container. The pH of the samples was also determined, and the suspensions were inspected for color, odor, and large particles. There was no significant decrease in carbamazepine concentration of more than 10% in samples stored for up to eight weeks. After 12 weeks, significant decreases in concentration were observed in all but one container type. No changes in color, odor, or consistency were observed during the 12 weeks, and there were no significant changes in pH. In commercially available suspension repackaged in volumes corresponding to common pediatric doses, carbamazepine (20 mg/mL) is stable for at least eight weeks when stored at room temperature in the containers tested.     

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 phenylephrine hydrochloride injection in polypropylene syringes.

PURPOSE: The stability of extemporaneously prepared phenylephrine hydrochloride injection stored in polypropylene syringes was studied. METHODS: Dilution of phenylephrine hydrochloride to a nominal concentration of 100 mug/mL was performed under aseptic conditions by adding 100 mg of phenylephrine hydrochloride (total of 10 mL from two 5-mL 10-mg/mL vials) to 1000 mL of 0.9% sodium chloride injection. The resulting solution was drawn into 10-mL polypropylene syringes and sealed with syringe caps. The syringes were then frozen (-20 degrees C), refrigerated (3-5 degrees C), or kept at room temperature (23-25 degrees C). Four samples of each preparation were analyzed on days 0, 7, 15, 21, and 30. Physical stability was assessed by visual examination. The pH of each syringe was also measured at each time point. Sterility of the samples was not assessed. Chemical stability of phenylephrine hydrochloride was evaluated using high-performance liquid chromatography. To demonstrate the stability-indicating nature of the assay, forced degradation of phenylephrine was conducted. Samples were considered stable if there was less than 10% degradation of the initial concentration. RESULTS: Phenylephrine hydrochloride diluted to 100 microg/mL with 0.9% sodium chloride injection was physically stable throughout the study. No precipitation was observed. Minimal to no degradation was observed over the 30-day study period. CONCLUSION: Phenylephrine hydrochloride diluted to a concentration of 100 mug/mL in 0.9% sodium chloride injection was stable for at least 30 days when stored in polypropylene syringes at -20 degrees C, 3-5 degrees C, and 23-25 degrees C.