Enhancing Micronization Processes with SYLOID^® Mesoporous Silica

Micronization, the process of reducing API particle size, is crucial for enhancing dissolution rates and bioavailability. This step is particularly important for APIs requiring fine particle sizes to ensure consistent drug loading in oral solid dosage forms. However, jet milling, the typical process used to grind materials into fine powders, often leads to challenges like poor powder flow and static issues, hindering downstream processes. We set out to find a better way to micronize APIs using mesoporous silica to enhance the process. Together with Microsize, North America’s largest independent pharmaceutical micronization company, Grace conducted a series of experiments to explore how adding SYLOID^® mesoporous silica can help mitigate these challenges and significantly improve outcomes.

Improving Run Time and Yield with Mesoporous Silica

Feed rate and manifold pressure are two critical operating parameters that have the greatest impact on the final particle size. The goal is to achieve a consistent feed rate, as well as reduce blockages inside the mill so as not to starve or overfeed the milling chamber.

The first experiment evaluated whether the addition of different concentrations of SYLOID^® mesoporous silica could prevent build-up inside a jet mill, using cholesterol as the active ingredient. Cholesterol was selected because it is a waxy, difficult to process solid, with many of the same physical properties as many complex small molecules currently under development. The results demonstrated that run time and yield both significantly improved with small additions of SYLOID^® mesoporous silica, which would indicate similar positive outcomes for a difficult-to-micronize API.

Download Case Study 1 for complete details.

Mitigating Powder Flow and Static Issues with Mesoporous Silica

Co-processing or co-jet milling is an approach that can help resolve some of the static and flow issues, making downstream blending and formulation easier. This involves adding a low percentage of a functional excipient to the micronization process – selecting one already found in downstream formulations can help simplify the process. 

The second experiment evaluated the impact of various percentage additions of SYLOID^® 244 FP mesoporous silica on powder flow properties and static reduction, using acetaminophen and ibuprofen as model compounds. Testing was also conducted to evaluate the impact of pre-blended, post-blended or co-fed approaches. 

Download Case Study 2 to discover the results

As both of these case studies demonstrate, the integration of SYLOID^® mesoporous silica into micronization processes can help enhance powder flow, reduce static issues, improve run time, and boost yield for difficult-to-process APIs. This simple approach to augment jet milling not only enhances the physical properties of micronized materials but also streamlines downstream blending and formulation, offering substantial value to CDMOs and their clients, such as more efficient manufacturing times, minimized material loss, and a more consistent final product.