The stability tests revealed that the physio-chemical properties of the dispersible 75mg aspirin tablets weren’t maintained after repackaging into multi compartment compliance aids over 5 the week period.
A weight uniformity test was conducted to ensure an accurate and consistent dosage form. It was shown that there was a change in the mean weight of the tablets from 148.29 ± 0.0094 mg to 149.54 ± 0.0169 mg, with a 0.84% increase. The masses complied with the British Pharmacopoeial standards as they were between 80 and 250mg with a coefficient variance of less than 7.5%.8 Despite the requirements being met, this small but significant weight increase may be indicative of an uptake of humidity from the environment and a permeation of moisture through the compliance aid. Aspirin is hygroscopic9 and is rapidly hydrolysed to salicylic acid, its degradant on exposure to moisture.
According to the British Pharmacopeia (BP), the limit of salicylic acid (SA) content within a dispersible formulation is 3%10. Hydrolysis may cause product degradation, hence compromising bioavailability and reducing efficacy. The pharmacist must consider whether the degradation of the active pharmaceutical ingredient (API) will result in sub-therapeutic or toxic affect, with potentially serious implications for the patient. It is the responsible pharmacists” duty to guarantee the safe supply of medicines.
A chemical titration was used determine the content of aspirin. Before repackaging the amount of aspirin was found to be 69.48mg which then decreased to 69.22mg. In both batches the aspirin content failed to meet BP requirements as they weren’t within 95% -105% of the labelled amount of 75mg11. Again, this could be due to moisture uptake and hydrolysis, resulting in a reduction of the API and reduced therapeutic efficacy. This may compromise patient safety, resulting in sub therapeutic dosing. However, the values may not be accurate due to poor titration technique and human error whilst reading the titre values. Although salicylic acid content wasn’t tested, when weight gain is linked to water absorption the physiochemical properties may be altered and the concentration of degradant may increase12.
A study on aspirin 300mg dispersible tablets repackaged as whole and split tablets, demonstrated significant changes in the SA content. When comparing with original packaging, a greater percentage of SA was present in the tablets stored under accelerated conditions. The tablets had swollen, become discoloured and disintegrated easily, highlighting that both temperature and moisture accelerate degradation13. Physical appearances are important as alteration may discourage patients from administration, leading to compliance issues which may compromise safety. In future, SA and aspirin content could be analysed using high pressure liquid chromatography (HPLC) for increased precision and accuracy14.
Regarding weights, the variances may be down to error of the balance. It may also be caused by the non-uniformity in the particle size distribution and bulk densities of the tablets in their compression during manufacture18. For crushing strength batch 1 was found to have a mean strength of 37.5± 4.7668N and batch 2 36.2± 4.5277N. The reduction in strength is due to decreased compression force and less condensed particles, requiring less force to overcome the intermolecular forces. If the tablet is too hard it may not disintegrate in the requisite time, and if it too soft, it may not withstand patient handling or packaging. However, generally dispersible tablets have less physical resistance than regular tablets. It may be possible that moisture uptake may have affected excipients such as the binder allowing it to be crushed more easily.
A study conducted on dispersible lamotrigine tablets repackaged into compliance aids also demonstrated a reduction in hardness and 60 days into the study, a 21.9% reduction had been reported. Variations in hardness is common with friability and such changes are likely to alter the dissolution profile and bioavailability of aspirin, affecting its efficacy and performance12. Friability should be measured if the study was to be repeated, to determine tablets ease of chipping and breaking. The time taken for the tablet to disintegrate decreased from 20 to 12 seconds. Rapid disintegration leads to rapid dissolution which can potentially affect performance and bioavailability of a drug, hence impacting its shelf life. Common disintegrants which are chemically stable in original packaging can be hugely affected by moisture.
A study conducted on asprin, atenolol and lansoprazole showed a decline in stability profiles when repackaged into MCA’s for 8 weeks, particularly their disintegration times. A faster time was observed for aspirin and atenolol, however both complied with BP standards10. It has been demonstrated that moisture uptake associated with disintegrants can result in micro-cracks due to the disintegrant swelling, causing it to disintegrate quicker, affecting the medications performance15. According to BP, dispersible tablets disintegrate within 15 minutes, using water at 37° C7. Thus, the tablets complied with the requirements.
In future dissolution can be tested to measure the rate of drug release, providing an indication of the bio-availability of aspirin. A study on Sodium valproate 100mg tablets after repackaging and storage under various conditions showed variable dissolution compared to controls, with the most pronounced differences being demonstrated at 40°C/75% RH16. Many dissolution profiles indicated slower, and in certain cases incomplete, absorption of the drug, therefore affecting the bioavailability. The study was limited as environmental factors such as temperature and humidity weren’t accounted for, nor controlled. Tablets should be tested at differing temperatures and various humidity. These factors were not monitored and therefore we cannot account for any fluctuations that may have occurred. This may be measured using a hygrometer or a digital thermometer in the future.
Factors such as patient or pharmacist handling weren’t considered, therefore the results aren’t a reliable representation as different situations a patient may experience weren’t simulated, such as storage in a humid bathroom. Also, measurements were taken at week 5 and not varying time intervals, for example t = 3 weeks. The study period for which the tablets were stored was too short to observe major changes and greater degradation may have been apparent after 5 weeks. The safety of the use in polypharmacy was not tested as we didn’t combine other medications. A study stored dispersible aspirin tablets alongside 5 other medications for 5 weeks17. Although, no degradation was detected in these quantitative HPLC methods, this parameter should be tested in the future.