Pharma Research and Development

Statement of the Problem: Delivery via the lung represents a unique opportunity to circumvent the prostaglandin independent mucosal injury associated with the oral administration of NSAIDs, as it eliminates the direct GI exposures to these drugs. Furthermore, the pulmonary drug delivery route usually decreases the dose requirements by 10 to 20 folds. Additionally, a slower rate of respiratory decline is shown in cystic fibrosis patients on high, oral doses of IBU in comparison to placebo. Dry powder inhalation is the most versatile way of pulmonary administration of API. It allows numerous formulation variations and many different dry powder inhaler (DPI) devices to design a drug product matching therapeutic needs. The purpose of the present research was to formulate IBU dry powder inhalers (DPI) containing Carrageenan as a natural polymer and to indicate appropriate excipient and polymer to improve the aerodynamic properties of the DPI formulations.

Materials & Methods: Trehalose and leucine were dissolved in Carrageenan solution. IBU was added into the solution. The mixture was then sprays and dried with constant stirring using a Büchi Nanospray dryer B-90. The formulations were analyzed by thermogravimetry (Perkin Elmer 4000). The in vitro aerosolization performance was investigated using next generation impactor (Copley). In vitro dissolution studies were done with paddle over disc method USP apparatus 2.

Results & Discussion: Encapsulation efficiency and the Carr’s Index increased with increasing Carrageenan. The highest encapsulation efficiency value was 78.6±2.9. On the other hand, the process yield decreased with increasing carrageenan. The lowest process yield value was 71.16±1.7%. The fine particle fractions of the formulations were over 37.8±3.2% thanks to the nanospray dryer. The release of IBU was nearly complete within 8 hours with 1:1 drug: polymer.