Solid-State Stability of Theophylline Anhydrous in Theophylline Anhydrous-Polyvinylpyrrolidone Physical Mixtures

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Abstract
There are contradictory evidences in the literature concerning the role of excipients with a high affinity for water in the formulation when the formulation is exposed to moisture. A few reports indicate the stabilization of a drug in the presence of hygroscopic excipients. Other reports indicate the rapid moisture-induced changes of the drug in the presence of an excipient with high affinity for water. The objective of this study was to understand the effect of PVP and the relative humidity of storage on the solid-state stability of anhydrous theophylline. In this study, physical mixtures of theophylline anhydrous and polyvinylpyrrolidone were prepared in varying proportions. These mixtures were then stored in a range of humidities at room temperature. X-ray powder diffraction, moisture uptake, HPLC, and FTIR spectroscopy were used to monitor the physical and chemical changes occurring in the mixtures. A hypothesis is presented on the role of amorphous polymeric excipients in the formulation. The hypothesis agrees with the recent knowledge on the mobility of water associated with amorphous polymeric materials. The mechanism of protection by the PVP against the hydration of theophylline could be described as desiccant action. The efficiency of this desiccant action of PVP will then be dependent on the amount of water molecules in the system and the kinetics of reaching the equilibrium moisture content.