IN-VIVO AND STABILITY STUDIES OF DRY POWDER INSUFFLATION CONTAINING TERBUTALINE SULPHATE AND ITRACONAZOLE NANOPARTICLES FOR THE TREATMENT OF ASTHMA

The present research was envisaged on the development of dry powder to treat asthma. Terbutaline sulphate (a bronchodilator) and Itraconazole (an antifungal) were used in the present study for bronchodilation and allergy to Aspergillus fumigatus (fungi) using lactose and trehalose as excipients. Dry powder insufflations were prepared by physical mixing (milling) and spray drying, out of which spray dried formulations with lactose as excipient gave the best results in-vitro. Hence, spray dried formulations were preceded for further pharmacokinetic and stability studies. The pulmonary concentrations of Terbutaline sulphate and Itraconazole from TER – A (sd), ITR – A (sd), TER: ITR – A (sd) monotonically decreased (T_max = 0 min). However, Itraconazole showed higher AUC0-α in individual and combined formulation when compared to Terbutaline sulphate showing slower elimination of Itraconazole. From plasma pharmacokinetic data T_max of Itraconazole formulations ITR – A (sd), TER: ITR – A (sd) was high when compared to the formulations of Terbutaline sulphate TER – A (sd), TER: ITR – A (sd) showing lower systemic bioavailability of Itraconazole when compared to Terbutaline sulphate. Stability studies for Drug content and in-vitro dispersion performance were conducted and results showed a decrease in drug content when kept at 40 ± 2 ºC and 75% ± 5% RH. The MMAD and GSD values were increased (from 4.67 µm to 6.32 µm whereas the GSD values were 2.24-3.48 µm) on stress conditions during accelerated, intermediate and long term stability studies.