An Investigation on the Effect of Polyethylene Oxide Concentration and Particle Size in Modulating Theophylline Release from Tablet Matrices

Abstract

Polyethylene oxide has been researched extensively as an alternative polymer to hydroxypropyl methylcellulose (HPMC) in controlled drug delivery due to its desirable swelling properties and its availability in a number of different viscosity grades. Previous studies on HPMC have pointed out the importance of particle size on drug release, but as of yet, no studies have investigated the effect of particle size of polyethylene oxide (polyox) on drug release. The present study explored the relationship between polymer level and particle size to sustain the drug release. Tablets produced contained theophylline as their active ingredient and consisted of different polyethylene oxide particle size fractions (20-45, 45-90, 90-180 and 180-425 μm). It was shown that matrices containing smaller particle sizes of polyox produced harder tablets than when larger polyox particles were used. The release studies showed that matrices consisting of large polyox particles showed a faster release rate than matrices made from smaller particles. Molecular weight (MW) of the polymer was a key determining step in attaining sustained release, with the high MW of polyox resulting in a delayed release profile. The results showed that the effect of particle size on drug release was more detrimental when a low concentration of polyox was used. This indicates that care must be taken when low levels of polyox with different particle size fractions are used. More robust formulations could be obtained when the concentration of polyox is high. Differential scanning calorimetry (DSC) traces showed that particle size had no major effect on the thermal behaviour of polyox particles.

Keywords: DSC traces; particle size; polyox; sustained release; theophylline.

Fig. 1

Effect of molecular weight and particle size on theophylline drug release containing of 20% polymer. a Polyox 750. b Polyox 303

Fig. 2

The effect of particle size and molecular weight of PEO on water uptake (percentage weight gained)

Fig. 3

Effect of particle sizes on drug release from theophylline matrix tablets with 40% polymer concentration. a PEO 750. b PEO 303

Fig. 4

Effect of polyox concentration and molecular weight on drug release from theophylline matrix tablets containing polyox particles 20–45 μm

Fig. 5

Effect of polyox concentration and molecular weight on drug release from theophylline matrix tablets containing polyox particles 180–425 μm

Fig. 6

DSC traces of various particle sizes of PEO 750 and 303