This post is an update to the previous post made on 04-April-2023. Thanks to the wonderful responses we have received from our colleagues in the industry, we are happy to provide this more inclusive list.
When screening for lipids or polymers to be used in a formulation for a drug delivery system (DDS), microfluidics is the technology of choice. This is because the individual samples can be run at extremely small volumes with practically no waste. In the past, this has not been the case with solvent injection technology. At the small end of manufacturing volumes, there is product waste and minimum batch sizes tend to be higher. However, microfluidics is not currently as scalable as solvent injection systems. At some point, to meet high volume demands of the Clinic and Commercial launch, the manufacturing process must switch over to solvent injection equipment for nanoparticle production.
Homogenization and extrusion are both methods used in pharma to produce uniform and consistent particle sizes. Homogenization involves the use of a high-speed mixer (high shear), homogenizer, to break down particles and mix them together. The mixer operates at high speeds and applies mechanical forces to the particles, causing them to be broken down and dispersed uniformly throughout the solution. This method is effective for creating nanoparticles or emulsions. Extrusion is a process that involves pushing the materials through a small orifice to create a uniform shape or size. Commercially available equipment utilizing the mixing technologies previously mentioned is provided in the table directly below. You can also access the table as a pdf at the bottom of the page.
Drug Sponsors with expensive API costs will be the customers that prioritize encapsulation efficiency (EE) over other system characteristics. Overall, costs for nucleic acids (mRNA, DNA, etc.) are extremely high, and any customer is going to want as high of an EE as possible. Because the costs of nucleic acids are so high, the desire to stretch development dollars comes down to processing more samples with less volume/loss. EE that associates how much of the API is captured inside the LNP. High EE corresponds to higher drug efficacy.
What must be pointed out about the data is that EE is both manufacturing process and drug formulation specific. A 95% Encapsulation Rate does not mean that a Mixing System will encapsulate any API in an LNP 95% of the time. It means, however, when targeting a specific particle size (while using a particular set of lipids and a specific API), 95% of the API was trapped within the lipids. When the variables of the process parameters or formulation change, then this claim cannot be applied; Process Development activities will still be required to tailor the formulation to the specific LNP Mixing System, whichever currently in the market chosen.
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