Bovtenko V. Pharmaceutical development and standardization of medicinal products with salbutamol sulfate in the form of metered dose inhalers

It was demonstrated by the results of verification/validation that such analytical procedures as an identification of salbutamol sulfate (SS), assay of SS (for various tests in acceptable ranges of use), determination of salbutamol ketone and related impurities of SS in the pressurized metered dose inhalers (pMDIs) with norflurane are correct. The crystal structure, particle size distribution and solubility of SS were studied; the critical factors for the stability of the suspensions of SS were identified. It was shown by HPLC that SS in solutions is decomposed on the impact of hydrogen peroxide and UV light. The choice of metering valves and containers was substantiated based on the results of studies of extractables and leachables, as well as the elements released to pMDIs. According to the results of determination of the performance characteristics (delivered dose uniformity, fine particle dose, distribution on the stages of impactors, etc.), the choice of actuators was justified. The factors of risk for the quality of pMDIs were shown and feasibility of implementation a new quality characteristic – fine particle dose uniformity – was substantiated. Rational approaches to the use of apparatuses A, C, D, E during the study of pMDIs were established. Pharmaceutical development and standardization of two medicinal products with SS in the form of pMDIs was performed; the registration documentation for these preparations was prepared. The medicinal products were registered and launched.