Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling
Само за регистроване кориснике
2018
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The aim of this study is to develop nanosuspension of carvedilol (CRV) by wet media milling. Concentration of polymeric stabilizer (hydroxypropyl cellulose-HPC-SL), milling speed and size of milling beads were identified as critical formulation and process parameters and their effect on CRV particle size after 60 min of milling was assessed using a Box-Behnken experimental design. Optimized nanosuspension was solidified using spray drying and freeze drying and subjected to solid state characterization. Low stabilizer concentration (10%), low milling speed (300 rpm) with small milling beads (0.1 mm) were found as optimal milling conditions. Crystal lattice simulation identified potential slip plane within CRV crystals, where fractures are the most likely to occur. Calculated mechanical properties of CRV crystal indicates that low energy stress is sufficient to initiate fracture, if applied in the correct direction, explaining the advantage of using smaller milling beads. Only spray drie...d nanosuspension redispersed to original nanoparticles, while particle agglomeration during freeze drying prevented sample redispersion. Wet milling and spray drying did not induce polymorphic transition of CRV, while there is indication of polymorphic transition during freeze drying, making spray drying as the preferred solidification method.
Кључне речи:
Nanosuspensions / Nanocrystals / Wet media milling / Experimental design / Molecular modelling / Crystal polymorphismИзвор:
International Journal of Pharmaceutics, 2018, 540, 1-2, 150-161Издавач:
- Elsevier Science BV, Amsterdam
Финансирање / пројекти:
DOI: 10.1016/j.ijpharm.2018.02.011
ISSN: 0378-5173
PubMed: 29438724
WoS: 000427584900015
Scopus: 2-s2.0-85042093177
Институција/група
PharmacyTY - JOUR AU - Medarević, Đorđe AU - Đuriš, Jelena AU - Ibrić, Svetlana AU - Mitrić, Miodrag AU - Kachrimanis, Kyriakos PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3171 AB - The aim of this study is to develop nanosuspension of carvedilol (CRV) by wet media milling. Concentration of polymeric stabilizer (hydroxypropyl cellulose-HPC-SL), milling speed and size of milling beads were identified as critical formulation and process parameters and their effect on CRV particle size after 60 min of milling was assessed using a Box-Behnken experimental design. Optimized nanosuspension was solidified using spray drying and freeze drying and subjected to solid state characterization. Low stabilizer concentration (10%), low milling speed (300 rpm) with small milling beads (0.1 mm) were found as optimal milling conditions. Crystal lattice simulation identified potential slip plane within CRV crystals, where fractures are the most likely to occur. Calculated mechanical properties of CRV crystal indicates that low energy stress is sufficient to initiate fracture, if applied in the correct direction, explaining the advantage of using smaller milling beads. Only spray dried nanosuspension redispersed to original nanoparticles, while particle agglomeration during freeze drying prevented sample redispersion. Wet milling and spray drying did not induce polymorphic transition of CRV, while there is indication of polymorphic transition during freeze drying, making spray drying as the preferred solidification method. PB - Elsevier Science BV, Amsterdam T2 - International Journal of Pharmaceutics T1 - Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling VL - 540 IS - 1-2 SP - 150 EP - 161 DO - 10.1016/j.ijpharm.2018.02.011 ER -
@article{ author = "Medarević, Đorđe and Đuriš, Jelena and Ibrić, Svetlana and Mitrić, Miodrag and Kachrimanis, Kyriakos", year = "2018", abstract = "The aim of this study is to develop nanosuspension of carvedilol (CRV) by wet media milling. Concentration of polymeric stabilizer (hydroxypropyl cellulose-HPC-SL), milling speed and size of milling beads were identified as critical formulation and process parameters and their effect on CRV particle size after 60 min of milling was assessed using a Box-Behnken experimental design. Optimized nanosuspension was solidified using spray drying and freeze drying and subjected to solid state characterization. Low stabilizer concentration (10%), low milling speed (300 rpm) with small milling beads (0.1 mm) were found as optimal milling conditions. Crystal lattice simulation identified potential slip plane within CRV crystals, where fractures are the most likely to occur. Calculated mechanical properties of CRV crystal indicates that low energy stress is sufficient to initiate fracture, if applied in the correct direction, explaining the advantage of using smaller milling beads. Only spray dried nanosuspension redispersed to original nanoparticles, while particle agglomeration during freeze drying prevented sample redispersion. Wet milling and spray drying did not induce polymorphic transition of CRV, while there is indication of polymorphic transition during freeze drying, making spray drying as the preferred solidification method.", publisher = "Elsevier Science BV, Amsterdam", journal = "International Journal of Pharmaceutics", title = "Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling", volume = "540", number = "1-2", pages = "150-161", doi = "10.1016/j.ijpharm.2018.02.011" }
Medarević, Đ., Đuriš, J., Ibrić, S., Mitrić, M.,& Kachrimanis, K.. (2018). Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling. in International Journal of Pharmaceutics Elsevier Science BV, Amsterdam., 540(1-2), 150-161. https://doi.org/10.1016/j.ijpharm.2018.02.011
Medarević Đ, Đuriš J, Ibrić S, Mitrić M, Kachrimanis K. Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling. in International Journal of Pharmaceutics. 2018;540(1-2):150-161. doi:10.1016/j.ijpharm.2018.02.011 .
Medarević, Đorđe, Đuriš, Jelena, Ibrić, Svetlana, Mitrić, Miodrag, Kachrimanis, Kyriakos, "Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling" in International Journal of Pharmaceutics, 540, no. 1-2 (2018):150-161, https://doi.org/10.1016/j.ijpharm.2018.02.011 . .