Investigations of physicochemical properties of spray dried drug-excipient composites directed to inhalable products

Abstract

The studies in this thesis explored the solid state and inhalation properties of various systems produced by the spray drying technique. The work focused on the feasibility analysis of spray drying as a means of producing materials for pulmonary delivery. The chemical and physical stability of different processed systems have also been addressed. The drugs investigated were salbutamol base, formoterol fumarate dihydrate, budesonide, bendroflumethiazide, hydroflumethiazide and hydrochlorothiazide. In all cases the physicochemical characteristics were studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), infrared (IR) spectroscopy, powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The inhalation properties were investigated using the twin stage impinger. Different aspects of chemical and physical stability studies were examined. Spray drying of salbutamol base alone resulted in predominantly amorphous powdered products and the degree of amorphicity depended on the spray drying conditions. Difficulties in processing were observed with the drug exhibiting stickiness due to its low glass transition temperature. Co-spray drying of salbutamol base with sugars and PVP resulted in composite particles that demonstrated a lesser degree of particle fusion.