Optimization of an In Vitro Dissolution Test Method for Inhalation Formulations

Abstract

The aim of this research project was to investigate a potential standardized test method to characterize the dissolution properties of numerous formulation types available for pulmonary delivery. A commercially available dissolution tester was adapted for use as a testing apparatus by the incorporation of a membrane-containing holder. The holder was designed to enclose previously air-classified formulations so that they could be uniformly tested in the dissolution apparatus. Dissolution procedures, the apparatus, dose collection, medium, and test conditions were developed relying on USP General Chapter <1092>. To collect an active pharmaceutical ingredient (API) fraction from the devices for subsequent dissolution studies, aerodynamic particle separation on the membrane holder was achieved using the Next Generation Impactor (NGI) for two commercially available products, Ventolin HFA and Pulmicort Flexhaler. The dissolution profiles of budesonide (BD) and albuterol sulfate (AS) were successfully estimated by analyzing the amount of drug released from the membrane holder. This dissolution method may be applied to quality control studies for various inhalation products. In particular, the in vitro dissolution profiles of the drugs may provide an estimate of their dispersion characteristics, which directly relate to the device or aerosol performances.

Miniature In Vitro Dissolution Testing of Powders for Inhalation

“…Therefore, the Transwell setup was modified by inserting a spacer to lift the inserts, allowing the addition of stir bars. Furthermore, for substance-specific comparison of dissolution profiles, it is mandatory that particle size distribution, amount of drug loading on membrane, and particle distribution on the membrane are similar (8,(11)(12)(13). From Table 4 it can be seen that membrane loading is very similar for PC and PE membranes.…”

“…Several dissolution techniques for powders for inhalation have been described, such as the flow-through cell (7)(8)(9), the Franz diffusion cell (8)(9)(10), and the paddle apparatus equipped with a special sample holder (8,11,12). The common disadvantage of these apparatus is the nonphysiologically large amount of dissolution medium (60-1000 mL).…”

Dissolution Techniques for In Vitro Testing of Dry Powders for Inhalation

“…The paddle apparatus with membrane holder was developed by Son et al (10). The apparatus consists of a vessel with 1 l dissolution medium which is immersed in a water bath (Erweka DT70, Erweka, Heusenstamm, Germany).…”

Meeting Report: FIP/AAPS Joint Workshop Report: Dissolution/In Vitro Release Testing of Novel/Special Dosage Forms

“…The wax paper pieces were then placed into plastic histology cassettes that were dropped into vessels of a paddle apparatus. More recently, this same research group modified an NGI with removable impaction cups that could then be dropped into the paddle apparatus (58). In the past few months, two separate research groups have demonstrated the use of diffusion apparatus to assess dissolution rates for inhalables.…”