a particle size analyzer can be used to measure the size of the globules in the product. This instrument can measure the size of the globules down to the micron level.
The size of globules in semi-solid dosage forms is an important factor in the quality and performance of the product. The size of the globules in the formulation affects the release pattern, bioavailability, and stability of the drug. Smaller globules can disperse more effectively in the body and can provide faster and more consistent drug delivery. Additionally, smaller globules help ensure uniform distribution of the drug in the dosage form, reducing the risk of batch-to-batch variation. Determining the size of the globules also helps to ensure that the formulation meets the desired specifications, which is essential for regulatory approval. Determining globule size can also help identify potential problems, such as incomplete mixing or uneven distribution of the drug in the formulation. This can help to improve the product's performance and reduce the risk of adverse effects.
Changes in emulsion globule size not only indicate potential physical stability issues but can also change systemic or localized bioavailability. Suspended actives and emulsion globules are both prone to change over the shelf life of the product. However, understanding that systemic and localized delivery can be significantly altered by (1) lot-to-lot differences in particle/globule size distribution at the time of release and/or (2) changes in particle/globule size on stability emphasizes the need for robust and reproducible techniques for measuring particle/ globule size.
The biggest challenge for any particle size methodology is to develop a sample preparation technique that (1) has sufficient contrast from other product components to allow for accurate particle or globule counting and (2) does not alter the particle/globule size distribution due to dilution, evaporation, or other manipulation of the sample.
For emulsions of two liquids having different refractive indexes, optical microscopy provides a direct measure of globule size and globule size distribution, which may be an indicator of the physical stability of the emulsion, i.e., a critical material attribute.
Microscopy of topical pharmaceuticals is usually limited to bright-field microscopy and polarized light microscopy (PLM). Bright-field microscopy is the best technique for visualizing globule size in a pharmaceutical emulsion, i.e. cream or lotion.
Bright-field manual microscopy is the technique used during the development of a pharmaceutical emulsion to predict which Q1/Q2 combination of excipients (both with and without API) provides sufficient microstructure (Q3) to produce the cream or lotion having the greatest physical stability.
Automated microscopy offers the same sensitivity over the same size range as manual methods, with the advantage of removing operator variability and fatigue and greatly improving statistical robustness. USP <778> Method 2 testing is a compendial method.
ImageProVision patented software is the right solution for Globule size determination and Microstructure evaluation in semi-solid and Emulsions topical preparations which can determine Globule size minimum up to 0.5 µ using an optical microscope or even for nano size range by adapting SEM images.
For effective Globule Size Determination in semi-solid dosage forms, ImageProVison is offering three products that are 21CFR Part 11 compliant.