Asthma is considered as the most relevant
pulmonary disease which is located at bronchial airways and oral
theophylline is one of the most prescribed drugs for its treatment as it is inexpensive. However, the frequency of
theophylline side-effects has recently reduced its usage. Inhaled
theophylline has not been successful either, mostly due to the lack of retention in the airways and irritation. In this study,
theophylline was encapsulated in mucoadhesive
starch microspheres using an inverse
emulsion method.
Glutaraldehyde was applied as the cross-linker for some of
starch-derived
microspheres. Cross-linking reaction was studied by means of the FTIR. A central composite face (CFC) design was used to optimize manufacturing conditions in order to obtain the highest drug entrapment yield and ideal aerodynamic diameter range of 5-11 microm at which bronchial deposition is maximum. Optimized
microspheres were successfully reproduced using the model provided by CFC design and their experimental aerodynamic diameter and drug entrapment yield were in good correlation with predicted values. Drug release of optimized
microspheres was measured in
phosphate buffer solution. Both cross-linked and uncross-linked
microspheres showed biphasic Fickian type drug release (Higuchi Model). These new formulations may recover the role of this valuable drug in
asthma management.