FORMULATION AND EVALUATION OF ENGINEERED PHARMACEUTICAL FINE PARTICLES OF BUDESONIDE FOR DRY POWDER INHALATION (DPI) PRODUCED BY AMPHIPHILIC CRYSTALLIZATION TECHNIQUE: OPTIMIZATION OF PROCESS PARAMETERS

The purpose of this study was to produce of microparticles for Dry Powder Inhalation, produced by environmentally driven Amphiphilic crystallization technique process by using different nonionic surfactants at different concentration and at different processing parameters, for inhalation therapy. Budesonide, as one of the inhaled glucocorticosteroids, is widely used in the treatment of asthma by pulmonary delivery.The objective of the current work was to developed microcrystals by using Amphiphilic crystallization process with different nonionic surfactants at different processing parameters. Salvation of Budesonide in aqueous Cremophor EL and Tween 20(1:1) was investigated using HPLC. A response surface type central composite design were employed using Design-Expert 5.0 software (StatEase, QD Consulting, Penzance, UK) with the factors investigated were stirrer speed, antisolvent addition rate, Cremophor EL and Tween 20. The crystals were filtered and freeze dried.Optimize the process variables for narrow particle size distribution (PSD). Cremophor EL and Tween 20 were added as the stabilizers.  Freeze dried crystals were subjected to XRD, DSC and SEM analysis for stability. The PSD also depended on the balance of meso and micromixing determined by the crystallization conditions. Optimized formulation was identified and characterized to determine their suitability for pulmonary delivery by using MSLI. Optimized formulation showed the highest FPF loaded and FPF emitted of 42 (1%) and 69 ( 3%) respectively, depositing mainly on stages 3 and 4, with much lower amounts collected on the higher stages of the MSLI.