Comparative Stability of Vitamin K1 Oral Liquids Prepared in Sterile Water for Injection and Stored in Amber Glass Bottles and Amber Plastic Syringes.

The purpose of this study was to evaluate the stability of vitamin K1 oral liquids in Sterile Water for Injection when stored in amber glass bottles and amber plastic syringes under refrigerated conditions. Four 100-mL batches of vitamin K1 in Sterile Water for Injection were prepared in amber glass bottles to protect from light. One of the batches was divided into 1-mL aliquots, using amber plastic oral syringes, and capped. The prepared bottles and syringes were stored in a laboratory refrigerator. On each day of sampling, 1-mL aliquots were removed from each bottle and mixed with an equal volume of ethanol. Likewise, the contents of sample syringes were mixed with ethanol to achieve an assay concentration of 0.5 mg/mL. Recovery of vitamin K1 in the compounded samples was quantified against a United States Pharmacopeia reference standard. Quantification was achieved using a stability-indicating high-performance liquid chromatography with ultraviolent light detection method. Product stability is defined as 90% to 110% of the initial concentration. The percent recovery in the Sterile Water for Injection preparations in glass bottles remained above 90% for the 105-day duration of the study, but some samples stored in amber plastic syringes fell below 90% on day 21. Furthermore, a statistically significant difference (2-way ANOVA, P < 0.0001) emerged between syringes at day 0 and day 30, and this trend continued through the day 60, 90, and 105 samples. The only statistically significant difference found within the bottle-stored samples occurred on day 105 (versus zero, P = 0.0465), but the recovery on day 105 still exceeded 90%. Vitamin K1 in Sterile Water for Injection, stored in a refrigerated amber glass bottle, is stable for 105 days. This preparation can also be stored in amber plastic syringes, but this decreases the beyond-use date to 14 days.

Stability of a pyrimethamine suspension compounded from bulk powder.

PURPOSE: Development of a stability-indicating high-performance liquid chromatography (HPLC) method for pyrimethamine analysis, with subsequent application of that method to assess the 90-day stability of a pyrimethamine suspension compounded from bulk USP-grade pyrimethamine powder, is described. METHODS: A stability-indicating method of HPLC with ultraviolet detection specific to pyrimethamine was developed according to pharmacopeial recommendations and validated. The method was applied to investigate the stability of a 2-mg/mL pyrimethamine suspension in a vehicle consisting of Ora-Plus and Ora-Sweet (Perrigo) over a period of 90 days. Three replicate test preparations were stored at room temperature or refrigerated at 4.3-5.2 °C, and samples were analyzed in duplicate immediately after preparation and on study days 1, 2, 4, 7, 10, 14, 21, 30, 48, 60, 75, and 90. RESULTS: The 2-mg/mL suspension of pyrimethamine in Ora-Plus and Ora-Sweet retained 90-110% of the labeled potency to 90 days at both temperature ranges. However, color changes in the samples stored at room temperature observed at day 60 indicated that a beyond-use date less than 90 days from the preparation date should be specified when the suspension is to be stored at room temperature. CONCLUSION: The study demonstrated that USP-grade pyrimethamine powder can be formulated as a 2-mg/mL suspension in a vehicle of Ora-Plus and Ora-Sweet and is stable when stored at room temperature and when refrigerated, in amber plastic bottles, for 48 and 90 days, respectively.

Beyond-use dating of lidocaine alone and in two "magic mouthwash" preparations.

PURPOSE: Beyond-use dating (BUD) of lidocaine alone and in two "magic mouthwash" preparations stored in amber oral syringes at room temperature was determined. METHODS: Two formulations of mouthwash containing oral topical lidocaine 2% (viscous), diphenhydramine 2.5 mg/mL, and aluminum hydroxide-magnesium hydroxide-simethicone were prepared in 1:1:1 and 1:2.5:2.5 ratios, divided into 3-mL samples, and stored in unit-dose oral amber syringes. Unit-dose single-product lidocaine samples were also prepared to serve as controls and stored in oral amber syringes. The lidocaine concentrations in these samples were measured periodically for 90 days. A stability-indicating high-performance liquid chromatographic method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity, and robustness. RESULTS: Based on the calculated percentages versus the initial concentration and the results from an analysis of variance comparing the two formulations, a BUD of 21 days is deemed appropriate for both magic mouthwash formulations. Based on the stability data, published safety concerns, and lack of efficacy in combination, packaging and dispensing lidocaine separately from other ingredients are recommended when administering magic mouthwash mixtures. Utilizing a 90-day BUD, lidocaine can be packaged separately from other magic mouthwash ingredients in individual dosage units and applied to the oral cavity using the swish-and-spit method. The delivery of the diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone could be separated, allowing for a swish-and-swallow method of administration. CONCLUSION: A BUD of 21 days is recommended for lidocaine prepared with diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone in ratios of 1:1:1 and 1:2.5:2.5 and stored at room temperature in amber oral plastic syringes.