Introduction
Over 70 million patients in the world use a metered dose inhaler (MDI) for a variety of diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and other lung diseases characterized by obstruction of airflow and shortness of breath.
Compared to other drug formulations, MDI's have unique differences with respect to formulation, container, closure, manufacturing, in-process and final controls and stability. The composition of an MDI formulation is crucial particularly in defining the physical stability and the performance characteristics of a MDI. Knowledge and information about parameters like particle density, particle size distribution, particle morphology, polymorphic forms of the active, solubility profile etc. are important from a generic manufacturer's perspective for achieving bioequivalence relative to the reference listed drug.
Objectives
This application note presents a study investigating the bioequivalence of the active pharmaceutical ingredient (API) of generic and reference listed drug of the same MDI formulation from the perspective of particle morphology. It also investigates whether the difference in particle morphology observed is due to inherent difference in the source API or was introduced during the course of formulation process.Method
Both the MDI formulations (Innovator and Generic) were actuated on a microscopic glass slide from a distance of approximately 6 centimeters using the same device. The formulations constituted of the active pharmaceutical ingredient, ethanol, propellant and oleic acid. Out of these, the propellant and ethanol evaporated during the actuation process, droplets of oleic acid were found in trace amounts and the dispersed active particles were retained on the microscopic glass slide. Morphological characteristics of the particles were investigated by automated image analysis using the Morphologi G3.Result & Discussion
>> Download the full Application Note as PDFMalvern Instruments provides the materials and biophysical characterization technology and expertise that enable scientists and engineers to understand and control the properties of dispersed systems. These systems range from proteins and polymers in solution, particle and nanoparticle suspensions and emulsions, through to sprays and aerosols, industrial bulk powders and high concentration slurries. Used at all stages of research, development and manufacturing, Malvern’s materials characterization instruments provide critical information that helps accelerate research and product development, enhance and maintain product quality and optimize process efficiency. Our products reflect Malvern’s drive to exploit the latest technological innovations and our commitment to maximizing the potential of established techniques. They are used by both industry and academia, in sectors ranging from pharmaceuticals and biopharmaceuticals to bulk chemicals, cement, plastics and polymers, energy and the environment. Malvern systems are used to measure particle size, particle shape, zeta potential, protein charge, molecular weight, mass, size and conformation, rheological properties and for chemical identification, advancing the understanding of dispersed systems across many different industries and applications. Headquartered in Malvern, UK, Malvern Instruments has subsidiary organizations in all major European markets, North America, Mexico, China, Japan and Korea, a joint venture in India, a global distributor network and applications laboratories around the world. www.malvern.com severine.michel@malvern.com
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