Investigating the properties of polymers for pharmaceutical controlled release applications.

Abstract

The phenomenon that amorphous polymers are not in thermodynamic equilibrium at temperatures below their glass transition was observed by several scientists. Being in unstable non-equilibrium states, the amorphous solids undergo slow processes which attempt to establish equilibrium. This gradual approach to equilibrium is termed physical aging. Physical aging will affect all those temperature-dependent properties which change drastically and abruptly at T$\sb{\rm g}$, because it is a gradual continuation of the glass formation that sets in around T$\sb{\rm g}$. When the polymer is cooled to some temperature below T$\sb{\rm g}$, the transport mobility will be small but not zero. Since at this stage the free volume is greater than it would be at equilibrium, the volume will continue to decrease slowly. This contraction will be accompanied by a decrease in the transport mobility with concomitant changes in all those properties of the glassy polymer which depend on it. In the pharmaceutical film coating process, some low-molecular-weight diluents, plasticizers, are added to polymers to modify their physical properties and to improve their film forming characteristics. Aqueous film coating techniques have obtained a lot of attention in the pharmaceutical industry in recent years, since the aqueous, collidal latex or pseudolatex dispersions provide revolutionary coating capabilities for totally water-based systems at a time when solvent coating has become increasingly unattractive from cost, environmental, and safety standpoints. Therefore, the specific aims of this research are to: (1) study the effect of physical aging on the dissolutions of hydroxypropyl methylcellulose phthalate film-coated tablets and granules and correlate it with the mechanical behavior of free films; (2) investigate the effects of physical aging and plasticizers on the water permeability of cellulose acetate and polyethylene glycols film-coated tablets and correlate with the mechanical behavior of free films; (3) investigate the effects of plasticizer and physical aging on the mechanical and mobility properties of ethylcellulose organic solvent and aqueous based membranes and the effect of film forming temperature on the properties of latex films, and (4) correlate the effects of physical aging on the dissolution and permeation properties with changes in the mechanical properties of these polymer films and estimate long-term aging effects on the dissolution rates and water permeabilities of the controlled release polymer film coatings.