API & Excipient Particle Size Study

In the pharmaceutical industry, the particle size distribution (PSD) of active pharmaceutical ingredients (APIs) has become one of the indispensable parameters in the development and product quality control of generic drugs. The PSD of APIs and excipients affects the quality of drug products, such as solubility, bioavailability, content uniformity, and stability, by influencing the flow, mixing uniformity, and compressibility of the intermediates outputted from the process, and ultimately the safety, efficacy, and quality control of the drug products. The decision tree drawn in ICH Q6A provides direction for the specification of API particle size standards. The impact of PSD on product quality should be incorporated into the risk assessment system throughout the life cycle of generic drug development and production, and PSD should be reflected in the internal control standards for material quality, intermediate control standards, or product quality standards, so as to control the quality of drugs and ensure the consistency of production with the help of risk assessment tools.

Challenges of API particle size characterization in formulations:

• The irregular shape (non-spherical) of many pharmaceutical substances, especially APIs, complicates data interpretation.
• Agglomeration, instability, and other physicochemical changes that occur during the measurement process.

Figure 1. Schematic diagram showing the process of interactive/ordered blending. (Alyami, et al. 2017)

Our Service

According to the requirements of different tablet dissolution, the particle size of APIs should be controlled in different particle size segments in order to achieve maximum efficacy. Alfa Chemistry provides professional RLD particle size study solutions to accurately detect the particle size and size distribution of APIs and excipients, and to help you select and prepare the ideal generic drug particle size. We offer a practical solution for reverse engineering of RLD and generic drug consistency evaluation.

We develop our own in-house protocols to evaluate the particle size of APIs and excipients. We have three imaging technology platforms as described below. We can use any of the individual techniques or a mix of techniques. The criteria for controlling the particle size and distribution of a drug can be developed based on a combination of choices such as the type of drug, route of administration, and clinical needs. We will select the appropriate assay for you to study the particle size and distribution of the drug, and perform complete methodological validation and optimization.

Our Technology Platforms

Polarized Light Microscope Platform

We offer a polarizing microscope for direct observation of the surface size and shape of the particles, as well as for visual verification of the size data obtained by other test methods. The basic principle is that the magnified image of the particles is transferred to a computer, which counts the number of particles in a set size range to obtain the particle size distribution.

The microscope observation method is simpler and more convenient, and can determine the current degree of particle dispersion and whether there is agglomeration. The disadvantage is that the microscope method is less sampling volume, less representative, sometimes can not reflect the level of the entire sample. Thus, it is suitable for testing the particle size distribution of a narrow range of samples, not for quality and production control.

Laser Particle Sizer

We offer a light scattering method (laser particle size meter) to determine the particle size distribution of APIs or pharmaceutical preparations. Monochromatic light beam irradiation to the particles of the test material is the phenomenon of scattering. Since the energy distribution of the scattered light is related to the size of the particles, the size distribution of the particles can be calculated by measuring the energy distribution of the scattered light (scattering angle).

The measurement range of this method is from 0.02 to 3500 μm, and the instrument used is a laser scattering particle size distributor. According to the properties and solubility of the test material, the wet method or dry method can be chosen:

• Wet determination is used for the determination of the suspension of the test material or insoluble in the dispersing medium of the test material.
• The dry assay is used for the determination of water-soluble or solid test materials without a suitable dispersing medium.

Microscopic Raman Spectroscopy Platform

We can use Raman microspectroscopy, signal acquisition of the preparation, after software processing, the API signal statistics and analysis, measured in the preparation of API particle size. The advantage of this method is that the response to the signal of excipients in the drug is lower than that of API, which can reduce the interference of excipients in the drug to the API signal.

We Offer API Particle Size Studies for the Following Formulations:

• Solid oral dosage forms (tablets)
• Suspensions
• Emulsions
• Ointments
• Emulsions