Physical stability of moisture-sensitive tablets stored in a canister or as unit-dose

Background: Knowledge about the long-term stability of tablets outside the original container, e.g. as unit-doses, is limited. This leaves the pharmacist with the dilemma of seeking improved patient safety by use of unit-doses on one side, versus the lack of knowledge about the stability of the repackaged drug on the other. Aim: To screen the physical stability of moisture-sensitive repackaged tablets to identify those with the need for further chemical stability testing. Method: The physical stability of commercially available tablets (16 products) was investigated after 6 months of storage at ambient conditions in canisters for unit-dose production and after 3 months of storage as unit-doses in a climate chamber at 25°C/60% relative humidity (RH). Changes in appearance, colour and mass were investigated in addition to changes in disintegration time, friability and resistance to crushing. Results: The appearance and results of the physical tests for all products were acceptable and within the requirements of the European Pharmacopoeia, except for sodium valproate enteric-coated tablets (Orfiril). These tablets were significantly altered after 3 months of storage as unit-doses at 25°C/60% RH. However, when stored at ambient conditions the tablets complied with the tests. Conclusions: The current study was a screening study limited to the investigation of the physical stability of a selection of moisture-sensitive repackaged tablets. However, although the physical stability is acceptable, the chemical stability and dissolution rate may be altered. The physical tests outlined are simple but could be suitable for selecting candidates for further chemical stability testing. © 2017 The Society of Hospital Pharmacists of Australi

Comparing Two Methods of Tablet Manipulation to Adjust the Warfarin Dose in Paediatric Care

Tablets containing prescribed doses are not always available, and this is of particular importance in paediatric care where suitable age-appropriate formulations are generally lacking. To obtain a child-adjusted dose, tablets are manipulated in several ways; e.g., they may be dispersed in water before a fraction is extracted, or they may be split before the resulting fragment is dispersed. In this study, the accuracy attained through these manipulation methods was investigated for two generic tablets containing the anticoagulant warfarin. Tablets were dispersed in water (10 mL) before a fraction (10%) was withdrawn, alternatively tablets were split in half or quarter fragments before the fragments were dispersed in water. To investigate the contribution of variability from the different steps in the manipulation processes, the amount of warfarin recovered from the various dispersions was determined, as was the accuracy of the splitting. A validated UHPLC-method was used for quantitative determination of warfarin. Splitting of the tablets could result in deviation >30% from the ideal, theoretical weight. The amount of drug substance extracted as a fraction from the dispersed tablets deviated no more than 10% from the intended amount. To obtain the most accurate child-adjusted fraction dose of warfarin, the tablets investigated in this study should be dispersed and the desired proportion extracted. Practices that involve splitting tablets are likely to increase the variation, and should be avoided

Adjusting the dose in paediatric care: dispersing four different aspirin tablets and taking a proportion

Objectives: When caring for children in a hospital setting, tablets are often manipulated at the ward to obtain the right dose. One example is manipulation of tablets containing the slightly water-soluble substance aspirin, used in paediatric care as an antiplatelet agent. The evidence base, however, for choosing certain tablet formulations and manipulation methods over others for extraction of proportions is lacking. The aim of this study was to investigate the effect of tablet formulation and manipulation technique on the dose accuracy and precision attained when dispersing different commercially available aspirin tablets and extracting a small proportion suitable for children. Methods: The manipulation methods investigated simulated those observed in the paediatric clinic. Four tablet formulations—one chewable, one conventional and two dispersible—were dispersed in 10 mL water in a medicine measure. On (1) passive dispersion, (2) mixing by stirring with the syringe, or (3) stirring and pumping the dispersion in and out of the syringe, respectively, proportions (1 mL or 2 mL) were extracted and the doses recovered were determined using a validated UHPLC (ultra high-pressure liquid chromatography) method. Results: Fractions from the four different dispersed aspirin tablet formulations varied from 99% to 3% of that intended with the lowest degree of mixing, and from 96% to 34% of that intended with the highest degree of mixing. Only the dispersible tablets gave average doses within 20% of the intended dose. Conclusions: Fraction extraction from dispersed aspirin tablets only gave doses within 20% of intended for the dispersible tablets, and then only for some of the manipulation methods: ‘passive dispersion’ for the 75 mg dispersible tablet and ‘stirring and pumping’ for the 300 mg dispersible tablet. The tablets not intended for dispersion gave unsatisfactory results, outside 20%, regardless of manipulation method. The findings underline the importance of considering both tablet formulation and dose extraction technique when manipulations are required

A new method for pharmaceutical compounding and storage of anti-VEGF biologics for intravitreal use in silicone oil-free prefilled plastic syringes.

Intravitreal injections of antibody-based biologics targeting vascular endothelial growth factor (VEGF) are highly effective and have markedly decreased the risk of visual impairment associated with prevalent retinal diseases, such as neovascular age-related macular degeneration and diabetes macular oedema. The diseases are chronic in their nature, and most patients need long-term therapy to suppress disease activity. We previously reported a compounding method for repackaging and storage of aflibercept (Eylea), a commonly used anti-VEGF biologic, in silicone oil-coated plastic syringes without compromising drug stability or activity. In addition to improving safety and time spent per patient, compounding of anti-VEGF biologics enables single-dose vials to be split into multiple syringes, thereby considerably reducing waste and drug expenses. However, symptomatic silicone oil droplets may deposit in the eye's vitreous body after repetitive injections. To fully avoid this complication, we here report on a novel pharmaceutical compounding method using silicone oil-free syringes and a 33 G × 9 mm Low Dead Space Needle hub injection needle. We evaluate the method for three anti-VEGF biologics commonly used in ophthalmology: aflibercept, ranibizumab (Lucentis) and bevacizumab (Avastin). Our results show that compounding and storage for one week does not compromise the functional activity of the biologics and allows for safe and cost-effective compounding of anti-VEGF biologics for intravitreal injections in prefilled silicone oil-free syringes