Stability of sodium valproate tablets repackaged into dose administration aids

Abstract

Objectives Since sodium valproate, a commonly used antiepileptic drug, has been reported to be unstable in the presence of moisture, our objective was to investigate the effect of repackaging into dose administration aids. Methods Sodium valproate 100 mg immediate-release tablets were repackaged and stored for 56 days at accelerated conditions (40°C/75% relative humidity), room temperature (25°C) and under refrigeration (2-8°C). Samples were analysed at 3, 7, 10, 14, 21, 35, 49 and 56 days to determine chemical stability using high-performance liquid chromatography, while physical testing included assessment of weight changes and dissolution behaviour. Key findings The results revealed that the sodium valproate content in the tablets remained within the acceptable range of 90-110% under all storage conditions for 56 days. Physical stability, however, was not maintained, with a total weight gain of 12.36% under accelerated conditions over the 56 days. Samples stored under all conditions showed variable dissolution compared to the controls, with the amount of sodium valproate in solution following 45 min of dissolution testing below 75% for half of all the intervals determined. Conclusions Repackaging sodium valproate tablets into dose administration aids results in unacceptable weight variation and changes in the dissolution profiles.

Quality Assurance of Medicines in Practice

“…Sodium valproate, a commonly used antiepileptic is unstable in the presence of moisture due to its hygroscopic and deliquescent nature. The results revealed that while the sodium valproate content in the tablets remained within an acceptable range (90-110% of the labelled amount) under all storage conditions for eight weeks, the physical stability was not maintained, with unacceptable weight variation in the tablets, changes in their dissolution profiles and significant changes in their appearance, under accelerated conditions, due to the hygroscopicity of the API, even after only three weeks of storage ( Figure 2) (Llewelyn, Mangan et al, 2010). The results of this study highlight the fact that accelerated conditions of temperature and humidity should be taken into account, and that cognisance is taken from the fact that in different countries, and in fact within the same country, the climatic conditions might vary considerably.…”

“…These aids have been used to facilitate medication administration to patients for over 30 years and their wider application has been strengthened by various government programs worldwide to facilitate their use (Llewelyn, Mangan et al, 2010). A community pharmacy contractual framework in the UK now places emphasis on assessing and providing practical compliance aids to all patients who fall within the protection of the Disability Discrimination Act 1995 and need help with medicine taking (Chan, Swinden et al, 2007).…”

“…Stability considerations Literature reference Aspirin Moisture sensitive (Haywood, Llewelyn et al, 2011) Atenolol Light sensitive (Chan, Swinden et al, 2007) Clozapine Oxygen sensitive (Perks, Robertson et al, 2011) Frusemide Light sensitive (Bowen, Mangan et al, 2007) Paracetamol Moisture sensitive (Haywood, Mangan et al, 2006) Prochlorperazine Light sensitive ) Sodium valproate Hygroscopic (Llewelyn, Mangan et al, 2010) …”

“…Three studies (Haywood, Mangan et al, 2006;Llewelyn, Mangan et al, 2010;Haywood, Llewelyn et al, 2011) have reported on the stability considerations of repackaging medicines that are hygroscopic or sensitive to moisture. The medicines were exposed to controlled room temperature conditions and accelerated conditions (elevated temperature and relative humidity).…”

“…Llewelyn and colleagues (Llewelyn, Mangan et al, 2010) undertook a study on the stability of 100 mg sodium valproate tablets (Epilim, Sanofi-Aventis) repackaged into DAAs (WebsterPak®) and stored under various temperature and humidity conditions. Sodium valproate, a commonly used antiepileptic is unstable in the presence of moisture due to its hygroscopic and deliquescent nature.…”