TY - JOUR
T1 - A comparative study of dry and wet top-down milling approaches for the preparation of microparticle suspensions
AU - Méndez Cañellas, Fidel
AU - Al-Rifai, Noor
AU - Padrela, Luis
AU - Tajber, Lidia
AU - Khamiakova, Tatsiana
AU - Otava, Martin
AU - Geertman, Robert
N1 - Publisher Copyright:
© 2023
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Top-down milling methods are widely used in the pharmaceutical industry for the micronisation of active pharmaceutical ingredients (APIs). In this work, jet milling (dry milling) and microfluidisation (wet milling) were compared for the comminution of indomethacin and naproxen. A design of experiments (DoE) approach was used to setup the experimental work and determine the parameters that affect the average particle size of the API particles. The same API, excipient combinations, concentration and particle size were targeted to constitute the suspensions with both techniques, and the resultant particle size stability, solid state, and morphology were studied. Both techniques were successful in producing suspensions with a particle size of 1–10 μm and the most stable API solid form. The key parameters to mill particles to the target particle size, and a protocol to produce crystalline particle suspensions were established in this work highlighting the differences between methods.
AB - Top-down milling methods are widely used in the pharmaceutical industry for the micronisation of active pharmaceutical ingredients (APIs). In this work, jet milling (dry milling) and microfluidisation (wet milling) were compared for the comminution of indomethacin and naproxen. A design of experiments (DoE) approach was used to setup the experimental work and determine the parameters that affect the average particle size of the API particles. The same API, excipient combinations, concentration and particle size were targeted to constitute the suspensions with both techniques, and the resultant particle size stability, solid state, and morphology were studied. Both techniques were successful in producing suspensions with a particle size of 1–10 μm and the most stable API solid form. The key parameters to mill particles to the target particle size, and a protocol to produce crystalline particle suspensions were established in this work highlighting the differences between methods.
KW - Active pharmaceutical ingredients
KW - Design of Experiments
KW - Jet milling
KW - Microfluidisation
KW - Microparticle suspensions
KW - Stability
UR - http://www.scopus.com/inward/record.url?scp=85166225816&partnerID=8YFLogxK
U2 - 10.1016/j.powtec.2023.118829
DO - 10.1016/j.powtec.2023.118829
M3 - Article
AN - SCOPUS:85166225816
SN - 0032-5910
VL - 428
JO - Powder Technology
JF - Powder Technology
M1 - 118829
ER -