New analytical techniques to facilitate preformulation screening in propellant systems

Area of Science:

• Pharmaceutical Sciences
• Analytical Chemistry

Background:

• Pressurized metered dose inhalers (MDIs) require robust preformulation screening methods.
• Traditional methods for drug stability and content analysis in MDIs can be time-consuming and require significant sample volumes.

Purpose of the Study:

• To investigate the applicability of an online direct inject High-Performance Liquid Chromatography (HPLC) method for pharmaceutical preformulation screening in MDIs.
• To extend the method's utility for evaluating drug stability in propellant systems and analyzing MDI vials.
• To assess the feasibility of the method for various metered valve sizes.

Main Methods:

• Utilized an online direct inject HPLC technique for solubility determination and extended its application to drug stability studies.
• Analyzed MDI vials crimped with metered valves using the developed method.
• Performed through-life content analysis on single MDI vials to assess repeated sampling capabilities.
• Modified injection couplers to accommodate different metered valve volumes (50 and 100 microL).

Main Results:

• The online direct inject HPLC method proved effective for preformulation screening of pharmaceutical agents in MDIs.
• Through-life content analysis confirmed that single MDI vials can be repeatedly sampled for stability evaluation.
• The method successfully evaluated the stability of a model drug across various formulations with minimal sample usage.
• Feasibility was demonstrated for 50 and 100 microL metered valves after coupler modifications, with further adjustments needed for 25 microL valves.

Conclusions:

• The online direct inject HPLC method is a valuable tool for efficient preformulation screening of MDIs.
• The technique facilitates comprehensive drug stability evaluation and content analysis in MDI systems.
• Adaptations of the method show promise for analyzing various MDI valve sizes, enhancing its versatility.