Back to Search
Start Over
Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterisation
- Source :
- Li, S, Yu, T, Tian, Y, McCoy, C P, Jones, D S & Andrews, G P 2016, ' Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterisation ', Molecular Pharmaceutics, vol. 13, no. 9, pp. 3054–3068 . https://doi.org/10.1021/acs.molpharmaceut.6b00134
- Publication Year :
- 2016
-
Abstract
- Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal Tm, low melt viscosity, and rapid solidification upon cooling.
- Subjects :
- Niacinamide
Materials science
Chemistry, Pharmaceutical
Pharmaceutical Science
Ibuprofen
02 engineering and technology
030226 pharmacology & pharmacy
Cocrystal
Suspension (chemistry)
Matrix (chemical analysis)
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Suspensions
Drug Discovery
Organic chemistry
Isonicotinamide
Hot melt
Drug Carriers
Molecular Structure
021001 nanoscience & nanotechnology
Characterization (materials science)
Chemical engineering
chemistry
Reagent
Feasibility Studies
Molecular Medicine
Extrusion
0210 nano-technology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Li, S, Yu, T, Tian, Y, McCoy, C P, Jones, D S & Andrews, G P 2016, ' Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterisation ', Molecular Pharmaceutics, vol. 13, no. 9, pp. 3054–3068 . https://doi.org/10.1021/acs.molpharmaceut.6b00134
- Accession number :
- edsair.doi.dedup.....6aaacac98dc8b9d6547b76247fb25aae