Particle Characterization
in the Pharmaceutical Industry

The particle size distribution of active ingredients and excipients is an important physical characteristic of the materials used to create pharmaceutical products. The size, distribution and shape of the particles can affect bulk properties, product performance, processability, stability and appearance of the end product.

The link between particle size and product performance is well documented with regards to dissolution, absorption rates and content uniformity. Reducing particle size can aid the formulation of NCE’s with poor water solubility. Proper matching of active ingredient and excipient particle size is important for several process steps. Particle size analysis is an integral component of the effort to formulate and manufacture many pharmaceutical dosage forms. HORIBA Instruments can provide both the analytical tools and technical support required to help pharmaceutical companies characterize their particulate systems with confidence.

Interview with Dr. Rob Lee of Particle Sciences

Watch a two minute video detailing how HORIBA Scientific has partnered with Particle Sciences to provide world-class technology and support for their CDMO business.


Laser Diffraction

This is the most popular particle size analysis technique used in the pharmaceutical industry. This technology is fast, easy to use, flexible, and repeatable. The LA-960 Laser Diffraction Particle Size Analyzer offers unique advantages including:

  • Dynamic range from 10 nanometers – 5,000 microns
  • Automatic control of powder flow rate with the PowderJet accessory leads to repeatable dry measurements
  • Built-in USP <429> calculations 

Learn how the LA-960 could be used in your pharmaceutical lab by downloading these applications notes.

  • Wet Method Development (You need to be logged in)
  • Dry method Development (You need to be logged in)
  • Utilizing USP <429> (You need to be logged in)

Laser Diffraction Application: Biopolymer Nanoparticles used for Drug Delivery

Biodegradable polymers such as polylactic acid (PLA) are frequently studied as potential carriers for controlled release formulations of active pharmaceutical. Since PLA nanoparticles are often in the range of 50 – 500 nm using both laser diffraction and dynamic light scattering (DLS) could be used for size analysis, but laser diffraction has the advantage of also being able to detect aggregates above 1 micron.  The unique ability measure particles down to 30 nanometers and up to 5,000 microns makes the LA-960 uniquely qualified to measure the entire range of biopolymer nanoparticles used for drug delivery.

Download Application Note 196: Particle Size Analysis of Biopolymer Nanoparticles using Laser Diffraction (You need to be logged in).

Laser Diffraction Case Studies: Excipients

An excipient is an inactive substance used as a carrier for the active ingredients of a medication. In addition excipients can be used to aid the process by which a product is manufactured. Two common excipients – magnesium stearate and microcrystalline cellulose – were used as the samples for the wet and dry method development application notes. The LA-960 data shown below indicates the high degree of precision possible when following a structured approach to method development.

Magnesium Stearate - Measured with the LA-960 PowderJet

Microcrystalline Cellulose - Measured with the LA-960 AquaFlow


Dynamic Image Analysis

This processing is becoming more common in the pharmaceutical industry for applications where particle shape, high resolution, and images of the particles are important. The CAMSIZER Dynamic Image Analyzer provides high-resolution size and shape data for pharmaceutical products such as granules, globules, and to study the coating thickness on inert core spheres.

Roundness Comparison
Roundness Comparison for Two Globule Samples

Download Application Note 142: Determination Of The Roundness Of Globules In The Pharmaceutical Industry (You need to be logged in).

Download Application Note 177: Particle Size and Shape of Pharmaceutical Granules Using Dynamic Image Analysis (You need to be logged in).

View Webinar AP002: Dynamic Image Analysis of Pharma Granules (You need to be logged in).


Static Image Analysis

Large particle detection from an actuated dry powder inhaler (DPI).
Large particle detection from an actuated dry powder inhaler (DPI).

Static Image Analyzers like the PSA300 provide accurate particle size and shape distribution information from 0.5 to 1000 µm.  Leading pharmaceutical companies now use this technique for a variety of applications including characterization of pharmaceutical actives, screening excipients, supporting method validation, and inspecting  MDI's and DPI's.  The PSA300 Static Image Analysis sytem and Disperser Unit provides a complete turn key system that can be installed and validated in just a few days.

Download Application Note 169: Particle Characterization of MDIs (You need to be logged in).

Download Application Note 168: Particle Characterization of DPIs (You need to be logged in).

View Webinar AP001: Image Analysis of Solid Oral Dosage Forms

View Webinar AP017: Particle Size and Raman Evaluation of a Semi-Solid Dosage Form


Dynamic Light Scattering

Dynamic light scattering is the preferred technique for sub-micron particle size analysis. The SZ-100 Nanoparticle Analyzer measures particles size from 0.3 nanometer – 8 microns, zeta potential and molecular weight. The SZ-100 can be used for a variety of samples/applications including liposomes, dendrimers, proteins, viruses, and virus-like particles.

The HORIBA SZ-100 Nanoparticle Analyzer measures particle size, zeta potential, and molecular weight.
The HORIBA SZ-100 Nanoparticle Analyzer measures particle size, zeta potential, and molecular weight.

Protein Aggregation - Case Study

Protein Aggregation

The study of protein aggregation encompasses a broad range of interactions and mechanisms.  Many studies into this subject area investigate the aggregation of mis-folded proteins, which is thought to be responsible for many degenerative diseases.  Since aggregation typically leads to a physical change in protein size, particle size analysis has proven to be a useful experimental technique in this field.  Dynamic light scattering (DLS) is now widely used to study protein aggregation as described in the application note referenced below.

Download the application note on Monitoring Protein Aggregation Using Dynamic Light Scattering (You need to be logged in).

Liposomes - Case Study

Liposomes are bilayer vesicles made of phospholipids derived from natural or man-made materials.  They are mainly used in the pharmaceutical field for treatment of cancers as carriers of chemotherapeutic drugs to the tumor area.  The amount of drug loaded into the liposomes and the size of the liposomes play pivotal roles in the pharmacokinetic and pharmacodynamic parameters of the drug.  Hence accurate and rapid measurement of the size of liposomes is essential for novel and effective drug delivery systems.

The LB-550 data shown below shows the particle size distribution of liposomes after five passes through a 100 µm filter.

Liposomes

Download the application note on Particle Size Analysis of Liposomes (You need to be logged in).


Raman Mapping

Raman Mapping

The ARAMIS from the HORIBA Jobin Yvon Raman Division provides information on particle properties including size, shape and chemical identification within final products such as tablets. This data is useful for investigating content uniformity, polymorphism, coating thicknesses, component mapping, and differentiation between amorphous and crystalline phases.

Now with the just released fast Raman mapping options SWIFT™ and DuoScan™ whole tablets like the 12.5mm diameter tablet shown above can be mapped in 10 minutes or less.

Visit the Raman Spectroscopy home page.

Visit the Pharmaceutical Applications Note page.


Additional Applications


Particle Analyzers for Pharmaceutical Applications

LA-960

The LA-960 uses Mie Scattering (laser diffraction) to measure particle size of suspensions or dry powders. The speed and ease-of-use of this technique makes it the popular choice for most applications.

SZ-100 Nanopartica Series Instruments

Industry's widest range and highest precision measurement instrument for Nanoparticle characterization.

CAMSIZER Dynamic Image Analyzer

HORIBA's CAMSIZER features dynamic image analysis to provide rapid and precise particle size and particle shape distributions for dry powders and bulk material in the size range from 20µm to 30mm.

PSA300

The HORIBA PSA300 is a state of the art turn-key image analysis solution. Seamless integration of Clemex's powerful particle characterization software and an automated microscope with high resolution camera creates an intuitive, easy-to-use imaging workstation.

SA-9600 Surface Area Analyzer

HORIBA's breakthrough SA-9600 Series brings exceptional convenience and confidence to surface area and pore volume analysis. Now you can perform single-point surface area, multi-point surface area and total pore volume measurements with push-button ease.