Novel theophylline oral drops for pediatric use and biological evaluation.

Abstract

Asthma, a global public health issue, seriously affects the quality of the children´s life. Theophylline, a phosphodiesterase inhibitor, is a drug that has been employed in treating respiratory diseases. In fact, pediatric formulation of theophylline for this purpose does not exist. Purpose: For this reason, we embarked, as an objective, the development and pharmacological evaluation of a new oral theophylline formulation, and studied the protective effects of this novel theophylline formulation on asthma, particularly its action on airway inflammation and on the modulation of oxidative stress biomarkers in a standard experimental asthma model, using ovalbumin sensitized Balb/c mice. The new oral theophylline drops not only met the parameters of exact dose, rheology, compatibility, viscosity, pH, taste and stability: but also fulfills the specifications of the pharmacokinetic parameters validated by HPLC-UV and Mass Spectroscopy. In Vivo the results showed that theophylline significantly inhibited OVA-induced mucus production and inflammatory response, and considerably impaired OVA-induced generation of reactive oxygen species. The results suggest that the theophylline formulation relieves asthmatic airway inflammation. Besides, histological changes revealed lesions of lung cells in experimental animals treated with ovalbumin. We believe that this involves oxidative stress-responsive lipid peroxidation pathway; thus, highlighting its potential as a useful therapeutic agent in the management of asthmatic children.