New active ingredients often have the challenge that they are poorly soluble in aqueous media, such as gastric and intestinal fluids. This means that after oral administration, for example in the form of tablets, they are poorly absorbed into the body and transported to their site of action, and that a large proportion is excreted unused. In order to be able to apply these active ingredients reasonably, their dissolution rate must be increased. This can be achieved by comminuting the drug particles, which greatly increases the surface area available for dissolution of the active ingredients. If the comminution is carried out very effectively, drug nanoparticles are obtained which, however, are often not stable in the surrounding aqueous medium of the nanosuspension due to their large surface area. By drying these drug nanosuspensions with excipients that form a matrix, in which the drug nanoparticles are separated from each other, better storage stability can be achieved. In the joint publication of the Institute of Particle Technology with the Institute of Pharmaceutical Technology and Biopharmacy, it was investigated how formulation parameters affect the stability of the nanoparticles. Different sugars were considered as carrier materials and a direct positive influence of a high intrinsic dissolution rate of the sugars on the separation and stabilization of the nanoparticles was found. In order to provide an estimate of the distance between the nanoparticles in this case, a Raman microscopic method was developed to measure the depth of the distribution of chemical components in the surfaces of the carrier particles. It was demonstrated that in the case of easily soluble sugars, thicker layers are loaded with active ingredients. This leaves more space for the distribution of the drug nanoparticles and a larger mean particle distance can be calculated, which thus correlates with better stabilization.
The method developed and the correlations identified can provide practical support and make the industrial development of so-called "enabling formulations" more efficient, i.e. preparations that enable the use of poorly soluble active ingredients in the first place.
Original Article:
Wewers, M., Finke, J. H., Czyz, S., van Eerdenbrugh, B., John, E., Büch, G., Juhnke, M., Bunjes, H. & Kwade, A. Evaluation of the Formulation Parameter-Dependent Redispersibility of API Nanoparticles from Fluid Bed Granules. Pharmaceutics 14; 10.3390/pharmaceutics14081688 (2022). https://www.mdpi.com/1999-4923/14/8/1688