Aspects of Particle Science and Regulation in Pharmaceutical Inhalation Drug Products

Abstract

Pharmaceutical orally inhaled drug products such as metered dose inhalers (MDIs) and dry powder inhalers (DPIs) are used by millions of individuals worldwide to treat symptoms of asthma and chronic obstructive pulmonary disease (e.g., chronic bronchitis, emphysema). Other applications of these products are being developed including inhalation delivery of insulin and medication to treat pain and the symptoms of cystic fibrosis. Analysis and control of particulate matter are important aspects of the development of these drug products. This includes the development and control of particles of drugs delivered to the patient and the characterization and control of foreign particles that may contaminate the final product. The chemistry and manufacture of these products historically have been strictly regulated by the United States Food and Drug Administration (FDA), with many challenging regulatory requirements applied to analysis and control of particles. This paper provides an overview of some of the main areas of particle analysis in inhalation drug products and the current regulatory challenges pertinent to these areas.

Quality Control Tests for Ophthalmic Pharmaceuticals: Pharmacopoeial Standards and Specifications

“…This method filters the products through a 0.8 µm grey gridded filter. The filter is then counted microscopically at 100× to determine the number of particles [46]. Some articles cannot be tested meaningfully by light obscuration.…”

Cryo-crystallization under a partial anti-solvent environment as a facile technology for dry powder inhalation development

“…28,29 In case of non spherical particles, particularly elongated ones, the aspect ratio plays a key role. It is a fact that the cross sectional area of air way from trachea to alveoli decreases progressively causing enormous air resistance during inhalation.…”

“…the alveoli. 28,29 In the case of non spherical particles, particularly elongated ones, the aspect ratio plays a key role. If the smaller dimension (width or thickness) of the elongated particles is below 5 mm, they will reach the alveoli.…”

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“…Its advantages include direct administration to the site of action, rapid onset, avoidance of the first pass effect, and higher efficiency of the delivered drug. There are three types of formulations used for pulmonary delivery: pressurized metered dose inhalers (pMDI), dry powder inhalers (DPI), and nebulizers (1)(2)(3). pMDI is released at high velocity and requires a simultaneous inhalation by the patient.…”