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Amorphous drug dispersions with mono- and diacyl lecithin: On molecular categorization of their feasibility and UV dissolution imaging.

Abstract：

:There is a growing interest in drug-phospholipid complexes and similar formulations that are mostly solid dispersions with high drug load. This study aims to explore the feasibility of such phospholipid-based solid dispersions as well as to characterize them. A particular aim was to compare monoacyl phosphatidylcholine (PC) with the diacyl excipient. The solid dispersions were manufactured using a solvent evaporation technique and characterized by means of differential scanning calorimetry and X-ray diffractometry. Density functional theory was used to calculate molecular frontier orbitals of the different compounds. Finally, the dissolution properties were analyzed in a flow-through cell by means of UV imaging. It was found that the ability to form solid dispersions with the phospholipids containing amorphous or solubilized drug (at equimolar ratio with the lipid) was dependent on the drug's frontier orbital energy, the enthalpy of fusion, as well as the log P value. In a subsequent dissolution study, UV imaging revealed pronounced surface swelling of the solid dispersions. Only the monoacyl PC was found to substantially enhance in vitro dissolution compared to pure drug. The gained understanding will support a future development of solid drug dispersions using phospholipids as matrix components.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Gautschi N,Van Hoogevest P,Kuentz M

doi

10.1016/j.ijpharm.2015.06.039

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

218-30

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(15)30006-5

journal_volume

491

pub_type

杂志文章

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