The role of particle size analysis in the development of inhalation preparations

- Sep 11, 2020-

Inhaled medicine refers to a drug delivery method in which the medicine enters the lungs through a special drug delivery device and has a local or systemic effect, thereby achieving the purpose of preventing or curing diseases. In the field of research and development of inhalation preparations, particle size distribution is one of the important properties of powder. In order to ensure the efficacy of inhalation preparations, particle size analysis is very important.

Most APIs and some pharmaceutical preparations are in powder or granular form. The particles are the basic unit of the powder. The size of the particles is called the particle size. Drugs usually contain a specific range of inhalable particle sizes (eg, they may be deposited anywhere in the respiratory tract). The determination of the size range of the inhaled particle size is very important, because it affects the deposition area of the drug in the respiratory tract and whether it will cause an inhalation problem. In addition, the particle size distribution can be used as an argument to support the inhalation test.


The particle size distribution of inhaled preparations is a key indicator of quality control. Combined with the physiological structure of the bronchi and lungs, the particle size distribution of inhaled preparations is generally required to be about 5um. For the research and development of inhalation preparations, whether it is aerosol, powder mist or liquid mist, particle size analysis and detection are an indispensable part of the quality control of inhalation preparations, and play a vital role in the quality and performance of the product. . Inhalation preparations are also unique in terms of technology development and review and approval. It is necessary to comprehensively consider the product's prescription technology, quality control, drug delivery device, industrial production, and clinical application. Medicilon is familiar with the development process of various inhalation preparations, especially in the field of powder inhalation (DPI), atomized inhalation and nasal spray (Nasal Spray) preparations. Conduct research work in accordance with the requirements of domestic and foreign laws and regulations and guidelines.


For the rapidly developing dosage form in recent years-aerosol inhaler, it is inhaled by mouth, transported by the respiratory tract, and finally reaches the lungs to play a role. It has the characteristics of simple prescription and convenient medication. The deposition mechanism of atomized aerosol particles in the lungs includes impact, diffusion, interception, gravity sedimentation, and electrostatic effects. In this process, the nature of the particles, the geometry of the respiratory tract, and the breathing pattern will all affect the deposition of the drug. The particle size and particle size distribution largely determine the location and amount of deposition in the respiratory system, thereby affecting the efficacy of the drug. Inertial impact method (CI) and laser diffraction method (LD) are both in vitro particle size analysis methods for nebulized inhalants. The aerodynamic diameter characterization method and the equivalent volume diameter characterization method are currently commonly used particle size characterization methods.


In short, the particle size and particle size distribution of the drug may have a significant impact on the properties of the final drug, such as solubility, bioavailability, content uniformity, and dissolution. For clinical drugs, reducing the particle size may have a positive effect on the bioavailability; in general, as the particle size decreases, the particle size becomes fine and uniform, the specific surface area increases, the porosity increases, and the adsorption is enhanced. The solubility is enhanced, the affinity becomes larger, and the chemical reaction rate increases, which improves the dissolution of the drug.


From a safety perspective, if the particle size range is not properly controlled, dissolution and absorbance in vivo may be inconsistent between batches, and the peak and valley fluctuations of the blood concentration curve may be large, which may cause safety problems or increase adverse reactions. In short, the particle size control of the drug has an important impact on the effectiveness, stability and safety of the drug. For the development of inhalation preparations, the requirements for drug particle size are also very strict.