PHYSICOCHEMICAL CHARACTERIZATION OF SPRAY DRIED FORMULATION CONTAINING AMORPHOUS DRUG

Zafirlukast is a prescription drug for asthmatic patients. Amorphous zafirlukast is known to convert into the monohydrate form in presence of water or to convert into the crystalline form which has a decreased solubility and bioavailability. The aim of this study is to optimize dissolution and avoid phase transformation of drug, in order to assure drug stability and bioavailability. This research is divided into two stages which are: processing parameters optimization and the effect of excipients on the rate of dissolution, and Zafirlukast amorphous content after spray drying. The selected optimum processing parameters were used in the second stage of this research. The excipient used were lactose fast flow, mannitol, microcrystalline cellulose (Avicel PH-102), and dibasic calcium phosphate (Di-Tab). Drug content, scanning electron microscope (SEM), differential scanning calorimetry (DSC), x-ray diffraction (XRD), and dissolution were performed to determine if there is phase transformation of the drug during processing in the spray dryer or after compression into tablets. The results indicated that formulation composed of lactose as excipient, zafirlukast and SDS at 1:1 ratio, and processed at a flow rate of 10 ml / minute, inlet air temperature of 180 0C, and a spray pressure of 0.1 MPa produced particles and tablets of best physico-chemical properties and best drug dissolution (95% in 15 minutes). In conclusion, Spray drying technique is effective in reducing particle size and enhancing the morphology of the particles without inducing phase transformation of the active ingredient from amorphous to crystalline form.