Formulation Development

NIS Molecule

Transmission Electron Microscopy (TEM) is essential for comprehensive analysis in formulation development.

Formulation development is crucial in determining the manufacturability and bioavailability of dosage forms. The performance of the end product depends on the characteristics of the individual ingredients. Despite the wealth of analytical techniques that can determine the quantitative size and shape of particles, these often fail to provide a comprehensive picture of the whole physical product. In contrast, Transmission Electron Microscopy (TEM) can directly observe individual particles in a sample, and simultaneously provide information on a range of characteristics, including size and size distribution, lamellarity, gene and drug encapsulation, shape and composition, as well as the influence of storage conditions such as pH, temperature, and time. These are all important parameters to analyze and monitor during the formulation development process, to control the function of the formulation. 

  • Gene therapy products are complex formulations. They employ various types of vectors (such as lipid nanoparticles (LNPs), adeno-associated viruses (AAVs), or other virus-like particles (VLPs)) and are susceptible to degradation. The gene therapy vector may encounter various physical and chemical instabilities during its production, storage, and shipment due to the exposure of stress via environmental conditions such as thermal, shear, freeze-thaw, and light exposure. In addition, gene delivery vehicles such as AAVs are commonly modified to package a gene of interest for gene therapy, requiring close monitoring and control. The formulation development process of commercially viable gene therapy formulations is therefore a ubiquitous challenge.
  • In formulation development and delivery, 'nanoparticles' refers to particles that deliver gene or drug products or proteins to their target site. These include liposomeslipid nanoparticles (LNPs), and virus-like particles (VLPs). Reliable and comprehensive nanoparticle characterization is needed of many parameters of the nanoparticles for quality and process control, and to ensure safety and efficacy. 

Get accurate structural details on a per-particle basis with cryo-TEM.

A range of nanoparticle characterization techniques can be used to analyze, monitor and control parameters during formulation development. These techniques, while in common use, are often limited in accuracy, can require lengthy analysis times and generate averaged information that do not necessarily correlate with observed outcomes. Cryo-TEM, however, provides important structural details on a per-particle basis that cannot be captured by other methods, quickly visualizing individual particles in the size range of ~5-500 nm. 

Imagine gaining a more thorough understanding of the structural characteristics of your formulations earlier in development. NanoImaging Services’ deployment of cryo-TEM makes this possible. We have worked with many leading pharmaceutical and biotech companies to optimize nanoparticles and gene delivery vehicles early during their formulation development. Of the 26 major players in the global LNP drug delivery market (see figure 7 in this paper reviewing the landscape of research diversity and advancement of LNPs), we have worked with over one third. Partnering with us has enabled these companies to identify potential issues earlier, enabling them to focus on the formulations that are most likely to succeed.

Frequently Asked Questions

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