Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions

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Semjonov , K , Salm , M , Lipiäinen , T , Kogermann , K , Lust , A , Laidmäe , I , Antikainen , O , Strachan , C J , Ehlers , H , Yliruusi , J & Heinämäki , J 2018 , ' Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions ' , International Journal of Pharmaceutics , vol. 541 , no. 1-2 , pp. 188-197 . https://doi.org/10.1016/j.ijpharm.2018.02.039

Title: Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions
Author: Semjonov, Kristian; Salm, Maia; Lipiäinen, Tiina; Kogermann, Karin; Lust, Andres; Laidmäe, Ivo; Antikainen, Osmo; Strachan, Clare J.; Ehlers, Henrik; Yliruusi, Jouko; Heinämäki, Jyrki
Contributor organization: Division of Pharmaceutical Chemistry and Technology
Pharmaceutical Design and Discovery group
Faculty of Pharmacy
Preclinical Drug Formulation and Analysis group
Clare Strachan / Research Group
Formulation and industrial pharmacy
Drug Research Program
Jouko Yliruusi / Principal Investigator
Date: 2018-04-25
Language: eng
Number of pages: 10
Belongs to series: International Journal of Pharmaceutics
ISSN: 0378-5173
DOI: https://doi.org/10.1016/j.ijpharm.2018.02.039
URI: http://hdl.handle.net/10138/299408
Abstract: Solid dispersions (SDs) hold a proven potential in formulating poorly water-soluble drugs. The present paper investigates the interfacial phenomena associated with the bulk powder flow, water sorption, wetting and dissolution of the SDs prepared by a modified melt and quench-cooling (QC) method. Poorly water-soluble indomethacin (IND) was QC molten with solubilizing graft copolymer (Soluplus (R)) or polyol sugar alcohol (xylitol, XYL). The interfacial interactions of SDs with air/water were found to be reliant on the type (amorphous/crystalline) and amount of the carrier material used. The final SDs were composed of fused agglomerates (SOL) or large jagged particles (XYL) with good wetting and powder flow properties. The initial dissolution of IND was accelerated by both carrier materials studied. The QC molten SDs with amorphous Soluplus (R) significantly improved the dissolution rate of IND at pH 6.8 (79.9 +/- 0.2% at 30 min) compared to that of pure crystalline drug. The substantial improvement in the dissolution rate of IND was in connection with the amorphous state of the drug being stabilized by Soluplus (R) in the QC molten SDs. However, it is evident that a strong H-bond formation between the components in some regions of the QC molten SDs can limit the dissolution of IND. The QC molten two-phase SDs with a polyol carrier (XYL) showed rapid and continuous drug release without reaching a plateau.
Subject: particle properties
bulk powder behavior
dissolution
solid dispersion
polymer
HOT-MELT EXTRUSION
WATER-SOLUBLE DRUG
AMORPHOUS INDOMETHACIN
DISSOLUTION RATE
PHYSICAL STABILITY
MIXTURES
SIZE
BIOAVAILABILITY
FLOWABILITY
FORMULATION
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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