Stability of papaverine hydrochloride and phentolamine mesylate in injectable mixtures

The stability of papaverine hydrochloride and phentolamine mesylate combined in a single vial was studied. Injectable mixtures (10 mL) of papaverine hydrochloride 300 mg and phentolamine mesylate 5 mg (from two sources) were prepared by adding the contents of one vial of lyophilized phentolamine mesylate to the contents of one vial of papaverine hydrochloride injection. The vials were stored at 5 degrees C and 25 degrees C. Duplicate aliquots of the mixtures were obtained, and the concentrations of papaverine hydrochloride and phentolamine mesylate remaining at time 0 and after 1, 2, 5, 10, 20, and 30 days were determined in triplicate by a stability-indicating high-performance liquid chromatographic assay. The concentration of papaverine hydrochloride stored in the vials remained constant (less than 1% loss) over the 30-day period at both 5 degrees C and 25 degrees C. Phentolamine mesylate was less stable than papaverine but still retained more than 97% of its original concentration after 30 days at 5 degrees C and more than 95% of its original concentration at 25 degrees C. Papaverine hydrochloride and phentolamine mesylate are stable in injectable mixtures when stored for up to 30 days at 5 degrees C or 25 degrees C.     

Stability of fluorouracil, cytarabine, or doxorubicin hydrochloride in ethylene vinylacetate portable infusion-pump reservoirs.

The stability of fluorouracil, cytarabine, and doxorubicin hydrochloride in admixtures stored in portable infusion-pump reservoirs was investigated. Admixtures containing fluorouracil 50 or 10 mg/mL, cytarabine 25 or 1.25 mg/mL, or doxorubicin hydrochloride 1.25 or 0.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were placed in 80-mL ethylene vinylacetate drug reservoirs protected from light, and 1-mL quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 7, 14, and 28 days at 4, 22, or 35 degrees C. For each condition, three samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change, and pH. Evaporative water loss from the containers was measured. Fluorouracil was stable at all temperatures for 28 days. Cytarabine was stable for 28 days at 4 and 22 degrees C and for 7 days at 35 degrees C. Doxorubicin hydrochloride was stable for 14 days at 4 and 22 degrees C and for 7 days at 35 degrees C. No color change or precipitation was observed, and pH values were stable. Loss of water through the reservoirs was substantial only at 35 degrees C for 28 days. When stored in ethylene vinylacetate portable infusion-pump reservoirs, fluorouracil, cytarabine, and doxorubicin hydrochloride were each stable for at least one week at temperatures up to 35 degrees C. Cytarabine and doxorubicin hydrochloride showed decreasing stability at longer storage times and higher temperatures.     

Antitumor activity on line 10 hepatoma in strain 2 guinea pigs and pharmaceutical properties of quinonyl-MDP preparations

The pharmaceutical properties of quinonyl-MDP-66 were discussed with special reference to the stability of oil-in-water emulsion, distribution capacity into regional lymph nodes and tumor regressive activity. The oil-in-water emulsion of quinonyl-MDP-66, which was prepared by treatment of quinonyl-MDP-66 with squalane (25 x) and emulsified with aqueous solution of 5% HCO-60 and 5.6% d-mannitol, was kept in lyophylized state and used after reconstitution by the addition of water before use. The reconstituted suspension of quinonyl-MDP-66 in oil-in-water emulsion was stable for more than 24 hrs. The oil-in-water emulsion of quinonyl-MDP-66 as prepared above was effective for the distribution of quinonyl-MDP-66 into regional lymph node in rats and for the regression of line 10 hepatoma in strain 2 guinea pigs by intralesional injection.     

Encapsulation of proteins and peptides in milkfat: encapsulation efficiency and temperature and freezing stabilities

Encapsulation of aqueous protein solution was most efficient when the butter and protein solution emulsion was at 58 degrees C before dispersion into water, although encapsulation efficiencies were high between 46 and 66 degrees C. Capsules could be produced with no emulsifiers and an emulsion temperature of 66 degrees C but no capsules were formed when emulsion temperature was lowered to 38 degrees C. Capsules with encapsulated beta-casein peptides and with proteose peptone had similar low-temperature stabilities with a loss of about 10 per cent of the peptides after 24 h at 4 degrees C. However, capsules with beta-casein peptides were slightly more stable above 26 degrees C. Little diffusion of the haemoglobin from capsules occurred at less than 20 degrees C but above 32 degrees C capsules destabilized and the haemoglobin diffused out of the capsules. Capsules were stable after freezing at -90 degrees C and -18 degrees C and could be thawed and redispersed; a 15-25 per cent loss of capsules was observed during freezing. Concentrating capsules by removing all or one-half of the dispersion fluid did not increase stability to freezing.     

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.     

Physicochemical properties of macrogol ointment and emulsion ointment blend developed for regulation of water absorption

Pressure ulcers can form with excess pressure and shearing stress on skin tissue. Because pressure ulcer is often accompanies by exudates, selection of appropriate topical emulsion ointment is difficult. Blended ointments consisting of emulsion base and water-soluble base are clinically used for adjustment of wound moist environment. Because regulating the amount of wound exudates can enhance treatment efficacy, two new blended ointments were developed. LY-SL blended ointment consisted of lysozyme hydrochloride water-in-oil (w/o) emulsion (LY-cream) and sulfadiazine macrogol (polyethylene glycol) ointment (SL-pasta). TR-SL blended ointment consisted of tretinoin tocoferil oil-in-water (o/w) emulsion (TR-cream) and SL-pasta (TR-SL). LY-SL and TR-SL were applied to Franz diffusion cell with cellulose membranes for the evaluation of water absorption characteristics at 32 °C. Water absorption rate constants (mg/cm(2)/min(0.5)) were 12.5, 16.3 and 34.6 for LY-cream, TR-cream and SL-pasta, respectively. Water absorption rate constants for LY-SL and TR-SL (SL-pasta 70%) exhibited intermediate values of 21.2 and 27.2, as compared to each ointment alone, respectively. Because amount of water absorbed was linearly related to square root of time, it was suggested that water-absorbable macrogol was surrounded by oily ingredients forming matrix structure. This diffusion-limited structure may regulate water absorption capacity. This is the first report of physicochemical properties of macrogol ointment and emulsion ointment blend developed for regulation of water absorption. The blended ointment can properly regulate amount of exudates in wounds and may be useful for treatment of pressure ulcers.     

Promotion of intestinal drug absorption by milk fat globule membrane]

A soybean oil emulsion was prepared by using milk fat globule membrane (MFGM) materials as an emulsifier. Its stability and effect on the intestinal absorption of vitamin D3, amphotericin B and kanamycin were studied. The MFGM emulsion was as highly stable as a Tween 80 emulsion. When the MFGM emulsion was sonicated with ultrasonic disrupter, the emulsion became more stable. Quantification of vitamin D3 in the intestinal lymph indicated that the MFGM emulsion enhanced lymphatic absorption of vitamin D3. The recovered percentage of vitamin D3 emulsified with MFGM in the lymph was 1.4 times that by Tween 80, and 2.5 times that of oil-in-water suspension. Statistically significant difference was found among them (p less than 0.05). The volumes of an oil phase in the emulsion affected the absorption of vitamin D3. The recovered percentage of vitamin D3 from the lymph increased with reducing the volume of the oil phase. Sonication of the emulsion did not affect the intestinal drug absorption. Furthermore, the MFGM emulsion had no effect on the intestinal absorption of amphotericin B and kanamycin.     

Physical and chemical stability of gemcitabine hydrochloride solutions.

OBJECTIVE: To evaluate the physical and chemical stability of gemcitabine hydrochloride (Gemzar-Eli Lilly and Company) solutions in a variety of solution concentrations, packaging, and storage conditions. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test conditions included (1) reconstituted gemcitabine at a concentration of 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride or sterile water for injection in the original 200 mg and 1 gram vials; (2) reconstituted gemcitabine 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride injection packaged in plastic syringes; (3) diluted gemcitabine at concentrations of 0.1 and 10 mg/mL as the hydrochloride salt in polyvinyl chloride (PVC) minibags of 0.9% sodium chloride injection and 5% dextrose injection; and (4) gemcitabine 0.1, 10, and 38 mg/mL as the hydrochloride salt in 5% dextrose in water and 0.9% sodium chloride injection as simulated ambulatory infusions at 32 degrees C. Test samples of gemcitabine hydrochloride were prepared in the concentrations, solutions, and packaging required. MAIN OUTCOME MEASURES: Physical and chemical stability based on drug concentrations initially and after 1, 3, and 7 days of storage at 32 degrees C and after 1, 7, 14, 21, and 35 days of storage at 4 degrees C and 23 degrees C. RESULTS: The reconstituted solutions at a gemcitabine concentration of 38 mg/mL as the hydrochloride salt in the original vials occasionally exhibited large crystal formation when stored at 4 degrees C for 14 days or more. These crystals did not redissolve upon warming to room temperature. All other samples were physically stable throughout the study. Little or no change in particulate burden or the presence of haze were found. Gemcitabine as the hydrochloride salt in the solutions tested was found to be chemically stable at all concentrations and temperatures tested that did not exhibit crystallization. Little or no loss of gemcitabine occurred in any of the samples throughout the entire study period. However, refrigerated vials that developed crystals also exhibited losses of 20% to 35% in gemcitabine content. Exposure to or protection from light did not alter the stability of gemcitabine as the hydrochloride salt in the solutions tested. CONCLUSION: Reconstituted gemcitabine as the hydrochloride salt in the original vials is chemically stable at room temperature for 35 days but may develop crystals when stored at 4 degrees C. The crystals do not redissolve upon warming. Gemcitabine prepared as intravenous admixtures of 0.1 and 10 mg/mL as the hydrochloride salt in 5% dextrose injection and 0.9% sodium chloride injection in PVC bags and as a solution of 38 mg/mL in 0.9% sodium chloride injection packaged in plastic syringes is physically and chemically stable for at least 35 days at 4 degrees C and 23 degrees C. Gemcitabine as the hydrochloride salt is stable for at least 7 days at concentrations of 0.1, 10, and 38 mg/mL in 5% dextrose injection and 0.9% sodium chloride injection stored at 32 degrees C during simulated ambulatory infusion.     

Stability of intravenous admixtures of doxorubicin and vincristine

The stability of doxorubicin and vincristine in admixtures containing both drugs in 0.9% sodium chloride injection, 0.45% sodium chloride and Ringer's acetate injection, and 0.45% sodium chloride and 2.5% dextrose injection was studied. Doxorubicin hydrochloride was added to 30-mL quantities of each base solution to achieve initial doxorubicin concentrations of 1.40 mg/mL and to 0.9% sodium chloride injection to achieve concentrations of 1.88 and 2.37 mg/mL. Vincristine sulfate was added to each doxorubicin admixture to achieve vincristine concentrations of 0.033 and 0.053 mg/mL. All admixtures were protected from light and stored in polysiloxan bags that are used with portable delivery devices. Admixtures were kept at temperatures of 25, 30, and 37 degrees C. Samples withdrawn immediately after preparation and at 1, 2, 4, 7, 10, and 14 days were analyzed by high-performance liquid chromatography for content of each drug. The stability of doxorubicin was dependent on temperature and composition of the base solution. Analysis of data from the samples containing 0.45% sodium chloride and Ringer's acetate injection showed that doxorubicin concentrations were less than 90% of the initial concentration by 12 hours at 37 degrees C, 35 hours at 30 degrees C, and 62 hours at 25 degrees C, and visual changes occurred in all of these admixtures over the course of the study. Vincristine degradation also was most rapid in 0.45% sodium chloride and Ringer's acetate admixtures. Data analysis showed that concentrations of vincristine were less than 90% of initial after eight days at 25 degrees C, five days at 30 degrees C, and three days at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability and degradation kinetics of etoposide-loaded parenteral lipid emulsion

Etoposide was incorporated in lipid emulsion to develop an i.v. formulation, and improve its physical and chemical stability without addition of organic solvents, for use as a commercial formulation. High-pressure homogenization was used to prepare the lipid nanospheres and localize the drug at the surfactant layer. The particle size distribution and zeta potential were measured using photon correlation spectroscopy (PCS). Ultrafiltration was used to estimate the relative percentage of etoposide in each phase. The stability profile of etoposide in the lipid emulsion at various temperatures, pH values, and concentrations of drug was monitored by high performance liquid chromatography (HPLC). The degradation pattern of etoposide in lipid emulsion followed pseudo-first-order kinetics. The shelf life (T(90%)) of etoposide in lipid emulsion was estimated to be 47 days at 25 degrees C and it would be stable when stored for 427 days at 4 degrees C, which is a significant improvement compared with a stability of 9.5 days in aqueous solution at 25 degrees C. Etoposide in lipid emulsion and aqueous solution were both most stable at pH 5.0 with a half-life of 54.7 h and 38.6 min at 80 degrees C, respectively. The hydrolysis kinetics of etoposide in lipid emulsion was also shown to be dependent on the drug concentration.     

Stability of an analgesic-sedative combination in glass and plastic single-dose syringes

The stability of a combination of chlorpromazine hydrochloride (6.25 mg/mL), hydroxyzine hydrochloride (12.5 mg/mL), and meperidine hydrochloride (25 mg/mL) in glass and plastic syringes was studied. Syringes (glass 1.5 mL, plastic 3.0 mL) containing the combination drug solution were stored at 4, 25, and 44 degrees C. At 0,7,30,60,90,180, and 366 days after preparation, samples were visually inspected and tested for pH. Drug concentrations were determined by gas chromatography. No significant changes in drug concentration were apparent in any of the samples stored at 4 degrees C or 25 degrees C. Samples in both glass and plastic syringes stored at 44 degrees C turned yellow by day 30 and continued to darken throughout the study period. At the concentrations tested, chlorpromazine hydrochloride, hydroxyzine hydrochloride, and meperidine hydrochloride combined in glass or plastic syringes are stable for 366 days when stored at 4 degrees C and 25 degrees C. Degradation occurs at higher temperatures.     

Stability of famotidine 20 and 50 mg/L in total nutrient admixtures

The stability of famotidine in total nutrient admixtures (TNAs) containing dextrose, an intravenous fat emulsion (IVF), and high or low concentrations of amino acids was studied. Famotidine was added to TNA solutions to final concentrations of 20 and 50 mg/L. TNA 1 contained 20% dextrose, IVF 40 g/L, and amino acids 42.5 g/L, and TNA 2 contained 25% dextrose, IVF 25 g/L, and amino acids 21.25 g/L. Control solutions of TNAs 1 and 2 without famotidine were also studied. All solutions were stored at 4 degrees C for 24 hours and then at 20-22 degrees C for 24 hours. The solutions were observed for signs of creaming or coalescence and measured for pH, famotidine concentration, and particle size at 0, 24, and 48 hours. No signs of creaming or coalescence were observed in control or test solutions throughout the study period. Famotidine in TNAs 1 and 2 showed a less than 5% change in concentration over the 48-hour period. Neither time nor amino acid concentration had any significant effect on famotidine concentration. Similarly, there were no significant differences in emulsion particle size between control solutions and TNAs containing famotidine and no significant changes in particle size over time. Famotidine 20 and 50 mg/L is stable in the TNAs tested when stored at 4 degrees C for 24 hours and then at 20-22 degrees C for 24 hours. Famotidine did not appear to disrupt the integrity of the emulsion system.     

Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle.

In order to obtain a novel ocular formulation with a potential for prolonging pilocarpine activity, the drug (2.0%) was incorporated into a submicron emulsion containing soya-bean oil and lecithin as emulgator. The effect of drug incorporation into the emulsion on its physical stability and on the other hand, the potential of the vehicle to reduce drug degradation at pH higher than 5.0 was studied. The pH was adjusted to 6.5 or 5.0 and the physicochemical stability of the formulations was observed. The mean diameter of oily particles in the resulting emulsions measured by a laser diffractometer was 0.6-0.7 micron and this was larger than in a drug-free emulsion where a 0.33 micron value was measured. The formulations were physically stable for 6 months at 4 degrees C, but progressing chemical degradation of pilocarpine was noted at pH 6.5. At that pH nearly 8% of pilocarpine was degraded to isopilocarpine and pilocarpic acid, both in the emulsion and in the solution. Thus, it may be concluded that pilocarpine in submicron emulsion is not protected against degradation. The presence of pilocarpine changes the physical stability of the vehicle since the formulation was easily destabilized during autoclaving or at room temperature. In the presence of higher concentration of lecithin (2.4%) or co-emulgators (poloxamer 2.0% or Tween 80 0.5%) the mean droplet size in the emulsions was the same as in a drug-free system. However the emulsions containing poloxamer were not stable during storage. Viscosity of pilocarpine emulsions can be increased by addition of methylcellulose or sodium carmellose (1.0%), but an intensive creaming occurs in these systems. Pilocarpine base is less suitable for emulsion preparation than hydrochloride salt, and emulsions prepared at pH 5.0 show the most satisfying stability.     

Stability of cefazolin sodium in various artificial tear solutions and aqueous vehicles

The stability of cefazolin sodium reconstituted in four artificial tear solutions, two acetate buffer solutions, phosphate buffer solution, and 0.9% sodium chloride injection was studied. Cefazolin was reconstituted in Tearisol, Isopto Tears, Liquifilm Forte, and Liquifilm Tears; acetate buffer solution at pH 4.5 and pH 5.7; phosphate buffer solution at pH 7.5; and 0.9% sodium chloride injection. The solutions were stored at 4 degrees C, 25 degrees C, and 35 degrees C for seven days. All of the solutions were inspected for particulates, turbidity, color, and odor. Five assay determinations on each of three samples of each formulation were performed using a stability-indicating high-performance liquid chromatographic assay. Cefazolin stability was influenced primarily by pH and storage temperature. Reconstitution of cefazolin sodium in the alkaline tear solutions Isopto Tears and Tearisol and in phosphate buffer solution resulted in particulate and color formation at 25 degrees C and 35 degrees C. Turbidity was noted after cefazolin sodium was reconstituted in Isopto Tears. No color or precipitate formation was evident after seven days at 25 degrees C and 35 degrees C in the formulations of acidic pH containing Liquifilm Tears, Liquifilm Forte, 0.9% sodium chloride injection or acetate buffer solution as the vehicles. The extent of degradation of cefazolin was substantially higher in the formulations of alkaline pH than in those of acidic pH at 35 degrees C and 25 degrees C. All of the formulations retained more than 90% of their initial concentration when stored at 4 degrees C. Cefazolin sodium, when reconstituted in artificial tear solutions with an acidic pH, is stable for up to three days at room temperature.     

Stability of pibenzimol hydrochloride in commonly used infusion solutions and after filtration

The stability of pibenzimol hydrochloride was evaluated after reconstitution, after addition to several intravenous fluids, and after filtration. Vials containing pibenzimol hydrochloride 50 mg were reconstituted with 2.5 mL of 0.9% sodium chloride injection to 20 mg/mL. For determination of drug stability in intravenous fluids, vial contents were further diluted to 0.15 mg/mL by injection into glass containers and polyvinyl chloride (PVC) bags containing 250 mL of 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection. Pibenzimol concentrations were determined immediately after preparation and at various intervals after storage at 4-6 degrees C or 25 degrees C by means of a stability-indicating, high-performance liquid chromatographic technique. Vial contents were inspected visually for color changes, and pH was measured. Determinations were also made of the stability of pibenzimol 0.15 mg/mL in 0.9% sodium chloride injection after simulated infusions using a 0.22-micron filter set at 25 degrees C. All study solutions and admixtures retained more than 90% of the initial pibenzimol concentration. The greatest loss of drug (6-7%) occurred after 24 hours in lactated Ringer's injection in both glass and PVC containers and in 0.9% sodium chloride injection in PVC bags. No drug loss occurred as a result of filtration. Reconstituted pibenzimol hydrochloride and admixtures of pibenzimol in 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection in glass or PVC containers are stable for at least 24 hours at 25 degrees C. Filtration has no effect on stability.     

Stability of heroin hydrochloride in infusion devices and containers for intravenous administration

The stability of heroin hydrochloride in various drug-administration devices was studied. Heroin hydrochloride was supplied as the bulk powder by the National Institute on Drug Abuse and in the formulated dosage form by Evans Medical, Ltd. Stability was determined at concentrations of 1 and 20 mg/mL at room temperature (23-25 degrees C) and at 4 degrees C in a polyvinyl chloride (PVC) bag, a disposable glass syringe, and two disposable infusion devices. Studies at both concentrations also were conducted at 31 degrees C in the disposable infusion devices. All experiments were conducted in triplicate. A validated, stability-indicating, high-performance liquid chromatography assay was used. Heroin hydrochloride remained stable for a minimum of 15 days in the PVC bag and the Infusor infusion device at the tested temperatures and concentrations. In the glass syringe, heroin hydrochloride was shown to be stable for a minimum of 15 days at both 1 mg/mL and 20 mg/mL if refrigerated at 4 degrees C, whereas at room temperature it was stable for a minimum of 7 days at 1 mg/mL and for 12 days at 20 mg/mL. In the Intermate 200 infusion device, heroin hydrochloride was stable for a minimum of 15 days at both concentrations and all temperatures except for the 1 mg/mL concentration at 31 degrees C. In the latter case, stability was for a minimum of two days. No substantial changes in physical appearance or pH were observed in any of the containers under the conditions studied. Heroin hydrochloride can be repackaged in the disposable glass syringe, PVC bag, and each of the disposable infusion devices for routine clinical use.     

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.     

Effect of methylcellulose on the stability of oil-in-water emulsions

The objective of this study was to investigate how polymers used as auxiliary emulsifiers improve the stability of oil-in-water emulsions. One stable emulsion and three unstable emulsions were formulated with 30% mineral oil and an emulsifier blend of Tween® 40 and Span® 20. The stable emulsion (SE) contained 2% emulsifier blend optimized for maximum stability. One unstable emulsion, UEI, was formulated to contain 0.5% of the same emulsifier blend as the SE formulation. Two unstable emulsions were formulated to contain an unbalanced emulsifier blend, one with excessive hydrophilic emulsifier (UE2) and one with excessive lipophilic emulsifier (UE3). A series of emulsions was prepared containing increasing amounts of methylcellulose for each base emulsion. Creaming and change in particle size were measured to evaluate stability. The addition of the polymer to the stable emulsion caused instability leading to creaming and eventual oil separation. This effect of the polymer was more pronounced in UEI emulsions. However, the addition of the polymer improved the stability of the UE2 and UE3 series of emulsions. The polymer also caused a reduction in the particle size of UE3 emulsions and a proportionally larger increase in the viscosity of UE2 emulsions. These results suggest that (i) methylcellulose could act as a hydrophilic emulsifier only in the absence of Tween^® 40, (ii) methylcellulose and Tween^® 40 associate to form a complex and (iii) the concentration of Tween^® 40 is the determining factor for the stability of emulsions. A model of the methylcellulose-Tween^® 40 association and its effect at the mineral oil-water interface is proposed.     

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.     

Compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in multilayer polyolefin containers.

PURPOSE: The compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in 5% dextrose injection and 0.9% sodium chloride injection was studied. METHODS: Test solutions of ondansetron hydrochloride 0.16 mg/mL and methylprednisolone sodium succinate 2.4 mg/mL were prepared in triplicate and tested in duplicate. Total volumes of 4 and 2 mL of ondansetron hydrochloride solution and methylprednisolone sodium succinate solution, respectively, were added to 50-mL multilayer polyolefin bags containing 5% dextrose injection or 0.9% sodium chloride injection. Bags were stored for 24 hours at 20-25 degrees C and for 48 hours at 4-8 degrees C. Chemical compatibility was measured with high-performance liquid chromatography, and physical compatibility was determined visually. RESULTS: Ondansetron hydrochloride was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. Methylprednisolone sodium succinate was stable for up to 48 hours at 4-8 degrees C. When stored at 20-25 degrees C, methylprednisolone sodium succinate was stable for up to 7 hours in 5% dextrose injection and up to 24 hours in 0.9% sodium chloride injection. Compatibility data for solutions containing ondansetron hydrochloride plus methylprednisolone sodium succinate revealed that each drug was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. CONCLUSION: Ondansetron 0.16 mg/mL (as the hydrochloride) and methylprednisolone 2.4 mg/mL (as the sodium succinate) mixed in 50-mL multilayer polyolefin bags were stable in both 5% dextrose injection and 0.9% sodium chloride injection for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C.