The effect of polymeric excipients on the physical properties and performance of amorphous dispersions: Part I, free volume and glass transition.

Autor: Li J; Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, NJ, USA, jinjiang.li@bms.com., Zhao J, Tao L, Wang J, Waknis V, Pan D, Hubert M, Raghavan K, Patel J
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2015 Feb; Vol. 32 (2), pp. 500-15. Date of Electronic Publication: 2014 Aug 09.
DOI: 10.1007/s11095-014-1478-0
Abstrakt: Purpose: To investigate the structural effect of polymeric excipients on the behavior of free volume of drug-polymer dispersions in relation to glass transition.
Methods: Two drugs (indomethacin and ketoconazole) were selected to prepare amorphous dispersions with PVP, PVPVA, HPC, and HPMCAS through spray drying. The physical attributes of the dispersions were characterized using SEM and PXRD. The free volume (hole-size) of the dispersions along with drugs and polymers was measured using positron annihilation lifetime spectroscopy (PALS). Their glass transition temperatures (Tgs) were determined using DSC and DMA. FTIR spectra were recorded to identify hydrogen bonding in the dispersions.
Results: The chain structural difference-flexible (PVP and PVPVA) vs. inflexible (HPC and HPMCAS)-significantly impacts the free volume and Tgs of the dispersions as well as their deviation from ideality. Relative to Tg, free volume seems to be a better measure of hydrogen bonding interaction for the dispersions of PVP, HPC, and HPMCAS. The free volume of polymers and their dispersions in general appears to be related to their conformations in solution.
Conclusions: Both the backbone chain rigidity of polymers as well as drug-polymer interaction can impact the free volume and glass transition behaviors of the dispersions.
Databáze: MEDLINE
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