Stability of Dalteparin 1,000 Unit/mL in 0.9% Sodium Chloride for Injection in Polypropylene Syringes.

The stability of dalteparin 1,000 units/mL in 0.9% sodium chloride for injection stored in polypropylene syringes under refrigeration was examined. Dalteparin 1,000-units/mL syringes were prepared by adding 9 mL of 0.9% sodium chloride for injection to 1 mL of dalteparin sodium 10,000 unit/mL from commercial single-use syringes. Compounded solutions in 0.5-mL aliquots were transferred to 1-mL polypropylene syringes and sealed with a Luer lock tip cap and stored at refrigerated temperatures (2°C to 8°C) with ambient fluorescent light exposure. Syringes from three batches of dalteparin 1,000 units/mL were potency tested in duplicate by a stability-indicating high-performance liquid chromatography assay using a 0.5-mL sample at specified intervals. Visual and pH testing were performed on each batch. Samples were visually inspected for container integrity, color, and clarity. Samples for pH testing were prepared using a 1:1 dilution of dalteparin 1,000 units/mL in sterile water for injection and underwent duplicate analysis at each time point. High-performance liquid chromatography analyses showed a remaining percent of the initial dalteparin content at day 30 of 94.88% ± 2.11%. Samples remained colorless and clear with no signs of container compromise and no visual particulate matter at each time point. Throughout the 30-day study period, pH values remained within 0.3-pH units from the initial value of 5.84. Dalteparin 1,000 unit/mL in 0.9% sodium chloride for injection, packaged in 1-mL polypropylene syringes was stable for at least 30 days while stored at refrigerated conditions with ambient fluorescent light exposure.

Stability of Alprostadil in 0.9% Sodium Chloride Stored in Polyvinyl Chloride Containers.

The stability of alprostadil diluted in 0.9% sodium chloride stored in polyvinyl chloride (VIAFLEX) containers at refrigerated temperature, protected from light, is reported. Five solutions of alprostadil 11 mcg/mL were prepared in 250 mL 0.9% sodium chloride polyvinyl chloride (PL146) containers. The final concentration of alcohol was 2%. Samples were stored under refrigeration (2°C to 8°C) with protection from light. Two containers were submitted for potency testing and analyzed in duplicate with the stability-indicating high-performance liquid chromatography assay at specific time points over 14 days. Three containers were submitted for pH and visual testing at specific time points over 14 days. Stability was defined as retention of 90% to 110% of initial alprostadil concentration, with maintenance of the original clear, colorless, and visually particulate-free solution. Study results reported retention of 90% to 110% initial alprostadil concentration at all time points through day 10. One sample exceeded 110% potency at day 14. pH values did not change appreciably over the 14 days. There were no color changes or particle formation detected in the solutions over the study period. This study concluded that during refrigerated, light-protected storage in polyvinyl chloride (VIAFLEX) containers, a commercial alcohol-containing alprostadil formulation diluted to 11 mcg/mL with 0.9% sodium chloride 250 mL was stable for 10 days.

Stability of chlorothiazide sodium in polypropylene syringes.

PURPOSE: The stability of a solution of chlorothiazide injection diluted with sterile water and stored in polypropylene syringes under refrigerated conditions was investigated. METHODS: Chlorothiazide solutions were compounded by adding 20 mL of sterile water for injection to a 500-mg vial of chlorothiazide sodium for injection. Six batches of chlorothiazide solution (25 mg/mL) were compounded; 0.5-mL portions were transferred to 1-mL polypropylene syringes, which were sealed with a Luer tip cap and stored at refrigeration temperatures (2-8 °C) protected from light. Three batches were potency tested by stability-indicating high-performance liquid chromatography (HPLC) assay using a 0.5-mL sample from each batch at designated time points. Visual and pH testing were performed using the three remaining batches; the contents of two syringes per batch were combined and visually inspected for container integrity and solution color and clarity, with duplicate pH testing performed at each time point. RESULTS: HPLC analyses showed that the remaining percentage of the initial chlorothiazide content declined at an average daily rate of 1.4%, decreasing to 93% by day 6. All samples remained intact, clear, and colorless, with no visible particulate matter or precipitation observed throughout the study period. For all samples of chlorothiazide solution, pH values remained within the range of 9.2-10.0 throughout the 10-day study period. CONCLUSION: When packaged in 1-mL polypropylene syringes and stored protected from light at refrigerated conditions, a solution of chlorothiazide sodium injection in water was stable for six days.

Stability of tranexamic acid in 0.9% sodium chloride, stored in type 1 glass vials and ethylene/propylene copolymer plastic containers.

Tranexamic acid has recently been demonstrated to decrease all-cause mortality and deaths due to hemorrhage in trauma patients. The optimal administration of tranexamic acid is within one hour of injury, but not more than three hours from the time of injury. To aid with timely administration, a premixed solution of 1 gram tranexamic acid and 0.9% sodium chloride was proposed to be stocked as a medication in both the aeromedical transport helicopters and Emergency Department at Mayo Clinic Hospital--Rochester Saint Marys Campus. Since no published stability data exists for tranexamic acid diluted with 0.9% sodium chloride, this study was undertaken to determine the stability of tranexamic acid diluted with 0.9% sodium chloride while being stored in two types of containers. Stability was determined through the use of a stability-indicating high-performance liquid reverse phase chromatography assay, pH, and visual tests. Tranexamic acid solutions of 1 gram in 0.9% sodium chloride 65 mL were studied at predetermined intervals for 90 days in ethylene/propylene copolymer plastic containers, protected from light, and at both controlled room and refrigerated temperatures. Tranexamic acid solutions of 1 gram in 0.9% sodium chloride 50 mL were studied at predetermined intervals for 180 days in clear Type 1 borosilicate glass vials sealed with intact elastomeric, Flourotec-coated stoppers, stored protected from light at controlled room temperature. Solutions stored in the ethylene/propylene copolymer plastic containers at both storage temperatures maintained at least 98% of initial potency throughout the 90-day study period. Solutions stored in glass vials at controlled room temperature maintained at least 92% of initial potency throughout the 180-day study period. Visual and pH tests revealed stable, clear, colorless, and particulate-free solutions throughout the respective study periods.

Stability of nitroglycerin 110 mcg/mL stored in polypropylene syringes.

Various angiography procedures at Mayo Clinic (Rochester campus) require small bolus doses of injectable nitroglycerin. Commercially acquired containers of injectable nitroglycerin provide excessive amounts of drug for these procedural needs, so syringes were chosen as a container for dispensing of the dose needed. Due to nitroglycerin's known chemical attributes of volatility and sorption to plastic surfaces, careful consideration of the stability needs to be taken into account when storing in a syringe. Since there is a lack of stability information in the literature, we studied the stability of nitroglycerin in polypropylene syringes over 90 days. Methods used for this study consisted of a validated stability-indicating high-performance liquid chromatographic assay, visual appearance, and pH. Samples were stored protected from light at ambient controlled temperature and consisted of nitroglycerin 110 mcg/mL in 5% dextrose injection 10.1 mL in 12 mL Terumo polypropylene syringes. Samples were tested at intervals up to 90 days. Results from the visual portion of the study showed clear, colorless, and particulate-free solutions throughout the 90-day study period. The pH results started at 4.27 +/- 0.13 (day 0) and ranged from 4.19 +/- 0.17 to 4.92 +/- 0.43 throughout the study period. Potency test results revealed a day 0 concentration of 104.242 +/- 0.193 mcg/mL (batch 1) and 122.483 +/- 0.168 mcg/mL (batch 2). Results trended downward with percentage of day 0 concentration of 92.2% +/- 2.4% at day 14 and of 81.4% +/- 4.9% at day 90. Chromatographic profiles of the samples exhibited insignificant changes over the study period. The nitroglycerin peak was spectrally pure based on peak-purity analysis, suggesting that sorption to the polypropylene syringe is one possible reason for the concentration decline over time, but nitroglycerin is a volatile compound and loss through vaporization cannot be ruled out. Nitroglycerin 110 mcg/mL in 5% dextrose injection, packaged in Terumo polypropylene syringes with 10.1 mL aliquots, maintained 90% of syringe potency for 24 days when stored protected from light under controlled ambient conditions.

Nifedipine in compounded oral and topical preparations.

The purpose of this study was to evaluate nifedipine oral and topical compounding formulas and procedures. Topical preparations were compounded in Plastibase 50 W, using combinations of two drug sources and four types of light exposure. Oral preparations were compounded using combinations of two drug sources, two types of light exposure, and four suspending vehicles. Drug sources consisted of the contents of commercial nifedipine soft-gelatin capsules and nifedipine powder USP. Light exposures were ambient, red-shaded, gold-shaded fluorescent light. Topical formulations were assessed for potency, uniformity, and usability characteristics such as acceptable look and feel of the preparation. Oral formulations were assessed for potency, uniformity, and usability characteristics, such as acceptable look and taste of the preparation. Preparations which were compounded, in entirety, under gold-shaded fluorescent light with nifedipine powder USP as the drug source resulted in a potency of 90% to 110% of intended value. Preparations that were exposed to ambient or red-shaded fluorescent light at any time in the compounding procedure resulted in sub potent preparations. Nifedipine is sensitive to certain wavelengths of light resulting in rapid degradation. When exposed to fluorescent room light, significant degradation may occur in a time frame less than what may be required to compound a preparation, necessitating the need for compounding to take place under a spectrum of light that will not degrade the drug. Gold fluorescent lighting appears to prevent nifedipine degradation during compounding procedures. Concerning the drug source, the use of commercial nifedipine soft-gelatin capsules was problematic, while nifedipine powder USP is a suitable choice for the active pharmaceutical ingredient.

Stability of fentanyl 5 microg/mL diluted with 0.9% sodium chloride injection and stored in polypropylene syringes.

PURPOSE: The stability of fentanyl 5 microg/mL in 0.9% sodium chloride solution packaged in polypropylene syringes was studied. METHODS: Samples of fentanyl 5 microg (as the citrate) per milliliter in 0.9% sodium chloride injection were prepared and assessed for chemical stability using a validated, stability-indicating high- performance liquid chromatographic (HPLC) assay. A total of 12 syringe samples were submitted for chemical stability testing by HPLC. The syringes were protected from light and stored in controlled ambient conditions (23-27 degrees C and 55-65% relative humidity) in an environmental chamber. Three samples were tested initially and at each 30-day interval. Each syringe sample was tested with two determinations, using the average of the determinations for the assay result. Samples were assessed for pH and inspected for color and visible particulate matter. Stability was defined as the retention of 90-110% of the initial drug concentration at 30, 60, and 90 days. RESULTS: Fentanyl citrate injection maintained the appearance of a clear, colorless solution, with mean +/- S.D. pH values ranging from 4.13 +/- 0.01 to 4.52 +/- 0.02 throughout the study period. Recovery of fentanyl ranged from 99.86% +/- 0.29% to 102.74% +/- 1.60% of the initial concentration, with no detectable changes in the chromatographic profiles of all tested samples. CONCLUSION: Fentanyl 5 microg (as the citrate) per milliliter in 0.9% sodium chloride injection, packaged in polypropylene syringes and stored protected from light, was stable for at least 90 days in controlled ambient conditions.

Sterilization of glycerin.

PURPOSE: The sterilization of glycerin is described. SUMMARY: Glycerin is used in a wide variety of pharmaceutical formulations, including oral, otic, ophthalmic, topical, and parenteral preparations. Of the myriad uses for glycerin, some require a sterile solution. Due to the nature of dry heat sterilization with resulting equipment and validation needs, sterile filtration is the preferred sterilization method for glycerin at the Mayo Clinic Pharmacy Services Production Laboratory in Rochester, Minnesota. A practical procedure was attained with the use of a chemically compatible 0.22-microm capsule filter, peristaltic pump, and sterile tubing. The sterile tubing is attached firmly, with a twisting motion, to the hose barb ends of the filter. The peristaltic pump is set at minimum speed, and a sterile syringe is used to capture the sterile glycerin filtrate. After filtration, filter integrity testing using the bubble point test is performed on the filter used to sterilize the solution. Packaging was then completed by placing glycerin aliquots into unit-of-use sterile syringes, placing a sterile tip cap on each syringe, and labeling the syringe. End testing is needed for preparations, such as sterile glycerin, that are made from nonsterile components, regardless of sterilization technique. This quality-control testing includes but is not limited to visual checks, pH checks, and tests for bacterial endotoxins, particulate matter, and sterility. Beyond-use dating is then assigned based on chemical, physical, microbiological, and packaging considerations. CONCLUSION: A practical method for sterilization of glycerin by compounding pharmacists is attainable through the use of membrane filtration. Sterility assurance is achieved through appropriate validation, and quality-control checks must be completed before release of the injectable preparation.

A collaborative effort to comply with USP chapter 797 for compounding sterile preparations for investigational use.

PURPOSE: A collaborative effort between two pharmacy specialty areas for ensuring compliance with United States Pharmacopeia (USP) chapter 797 for compounded sterile preparations (CSPs) is described. SUMMARY: In September 2005, an investigational drug service (IDS) satellite was opened at a 1157-bed, level 1 trauma, academic hospital in Minnesota. After construction of the IDS satellite, a collaborative consulting service was established between the two pharmacy areas. Protocol-specific investigational medications requiring extemporaneous compounding were reviewed by both an IDS pharmacist and a hospital compounding pharmacist to provide recommendations to investigators. High-risk compounding was performed by the hospital compounding pharmacy, and patient-specific, medium- and low-risk compounding of CSP doses was performed by IDS pharmacy personnel for research participants. A small subset of investigational medications met high-risk criteria and was referred to the hospital compounding pharmacy. After final clearance from quarantine, the high-risk preparations were transferred to the inpatient IDS satellite for dispensing of patient-specific investigational medication doses. The compounding pharmacy followed standardized quality-assurance procedures to ensure sterility, purity, and endotoxin appropriateness for the investigational medications. Quality control of investigational CSPs was maintained by hand delivery of the investigational medication and documentation and disposition via hard-copy receipt on the nursing units. Based on chapter 797 requirements, the department of pharmacy's education and training changed to reflect the new compounding requirements for CSPs, including 20 hours of didactic training for aseptic manipulation skills and practical assessments of aseptic technique using growth media. CONCLUSION: A collaborative effort between two specialty areas of pharmacy services ensured compliance with USP chapter 797 requirements for compounded sterile preparations.