Which APIs are suitable for the nanomilling and Nanocrystal technology?
Low soluble APIs of BCS class II-IV having an aqueous solubility of less than 1 mg/ml. Also pH dependent soluble APIs are suitable as buffers can be used in the nanomilling process to run the process at a certain pH interval.
What scale is available for nanomilling at Losan Pharma?
Beside the screening scale with 50 -300mg API (depending on loading) per sample in our Delta Vita 1 with 40 samples in one run currently a lab and pilot scale with our Netzsch Delta Vita 300 up to 10L under full GMP can be offered. A production scale with 150 -600 L per batch in a nanomill from Netzsch can be offered in 2021.
What kind of media are used in the milling process?
Qualified high performance Yttria stabilised Zirkonoxide beads with different size from 0.1 – 1.0 mm are currently used.
Is there any significant residue from the milling beads found in the product?
No, the residues of Zirkonium found by using ICP-OES in the product were well below 10ppm, for Yttrium even lower.
What are the typical milling times seen for the products?
The milling time is mainly influenced by the coarse particles of the starting API, the hardness and brittleness of the API crystals. In case of micronized API´s the milling time is normally not exceeding 8 hours for a 10L batch.
What factors are influencing the stability of nanosuspensions?
The main factors influencing the stability of the metastable nanosuspensions are the nature of selection of the stabilising surfactant and polymers, the resulting Zetapotential, the concentration of the API and the nature of the API (weak base, salt.
What is the risk of changing polymorphs e.g. from crystalline to amorphous state of the API?
The risk is generally quite low and for most of the cases the crystallinity of the API is well maintained. However, a certain control by powder diffraction measurements should be done.
Is there any regulatory risk in conducting clinical trials with nanosuspensions or nanoparticulate dosage forms?
No, the nanoparticles obtained by nanomilling are above 100 nm in the mean size and do not influence the pharmacodynamics and distribution to organs in-vivo, but the resorption and resorption speed is increased by the nanoparticles leading to an increase in the tmax, Cmax and AUC values in the blood plasma.