Stability Implications of Repackaging Paracetamol Tablets into Dose Administration Aids

Abstract

Background: Despite the widespread use of dose administration aids (DAAs) there is little available data on the stability of drugs during repackaging or storage in these devices. Aim: To investigate the physicochemical stability of paracetamol tablets repackaged in DAAs. Method: Physicochemical stability studies were performed on a commonly used paracetamol tablet directly after heat-sealing in a DAA frequently employed in practice, then at ambient (25 ºC; 60% relative humidity) and accelerated (40 ºC; 75% relative humidity) conditions, over a 3-month period. Physical characteristics of the tablets (weight uniformity, physical appearance, thickness, hardness, friability, disintegration, dissolution rates) were evaluated at time = 0, directly after heatsealing, 1 month and 3 months. Chemical stability was confirmed by high performance liquid chromatography (HPLC). The results were compared to control samples stored in the original packaging at the various environmental conditions studied. Results: All compendial requirements for physicochemical stability were met for both ambient and accelerated conditions over the 3-month period. Chemical stability of paracetamol content fell within the required range of 95-105% of the labelled amount, for all environmental conditions. Conclusion: This study provides evidence on the stability of paracetamol tablets in a DAA, to support pharmacists in making sound clinical and operational decisions regarding the repackaging of paracetamol in these devices. J Pharm Pract Res 2006; 36: 25-8.

Quality Assurance of Medicines in Practice

“…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).…”

“…Haywood and colleagues (Haywood, Mangan et al, 2006) examined the stability implications of repackaging commonly used 500 mg paracetamol tablets (Panamax, Sanofi Synthelabo) in a DAA frequently employed in practice (Multidose WebsterPak®). Paracetamol has the potential to undergo hydrolysis and therefore requires protection from moisture.…”

Stability Studies of a Mixture of Paracetamol and Ascorbic Acid, Prepared Extempore, at Elevated Temperature and Humidity Conditions

“…Information on storage and preparation conditions is particularly important for patients living in tropical countries in III or IV climate zone, where climate conditions differ from those of I and II climate zone [6]. Paracetamol and ascorbic acid are commonly used organic ingredients of OTC medicinal products.…”

“…Additionally, paracetamol contains the amide group which may be sensitive to hydrolytic degradation. Research on medicinal products stored in different temperatures and humidity has shown that physical properties of paracetamol in the form of powder and solution remain unaffected for even as long as three months [12][13][14]. It is different in the case of ascorbic acid's stability which decreases with increased temperature, sun exposure and pH.…”