Authors:
S. Verheyen K. U. Leuven Laboratorium voor Farmacotechnologie en Biofarmacie Campus Gasthuisberg O+N Herestraat 49 3000 Leuven Belgium

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N. Blaton K. U. Leuven Laboratorium voor Analytische Chemie en Medicinale Fysicochemie Van Evenstraat 4 3000 Leuven Belgium

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R. Kinget K. U. Leuven Laboratorium voor Farmacotechnologie en Biofarmacie Campus Gasthuisberg O+N Herestraat 49 3000 Leuven Belgium

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G. Van den Mooter K. U. Leuven Laboratorium voor Farmacotechnologie en Biofarmacie Campus Gasthuisberg O+N Herestraat 49 3000 Leuven Belgium

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Abstract  

The effect of grinding on the physical properties and pharmaceutical performance of solid dispersions made of poly(ethylene) glycol 6000 (PEG6000) and temazepam or diazepam was studied using differential scanning calorimetry (DSC), X-ray powder diffraction and dissolution experiments. DSC-analysis of flash-cooled dispersions revealed that amorphous PEG present immediately after grinding crystallised upon aging mainly into the twice folded modification and to a small extent into the extended form. DSC-analysis of dispersions kept in the slab form for 1 month and subsequently ground, revealed that in the abscence of the grinding impulse crystallisation of PEG6000 takes place in the same way as in dispersions ground immediately after preparation and then aged for 1 month. Grinding solid dispersions immediately after preparation resulted in superior dissolution properties compared with solid dispersions kept in the monolith-slab form and subsequently ground. This difference in dissolution properties was found to be attributed to the drug and not to the polymer, more precisely, it was suggested that the drug particle size in ground dispersions was smaller than in dispersions kept in the slab form and subsequently ground. These findings suggest that grinding of solid dispersions immediately after preparation is the preparation method of choice instead of liquid filling of hard gelatin capsules resulting in monoliths.

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Journal of Thermal Analysis and Calorimetry
Language English
Size A4
Year of
Foundation
1969
Volumes
per Year
1
Issues
per Year
24
Founder Akadémiai Kiadó
Founder's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Springer Nature Switzerland AG
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
CH-6330 Cham, Switzerland Gewerbestrasse 11.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 1388-6150 (Print)
ISSN 1588-2926 (Online)

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