Dissolution rate enhancement of parabens in PEG solid dispersions and its influence on the release from hydrophilic matrix tablets.
The dissolution rate of a homologous series of parabens and their dispersions in PEG 4 × 10(3) was examined. In light of these measurements, the release behavior of the substances from extended release hydrophilic matrix tablets based on PEO 5 × 10(6) was studied. Tablet release was examined for matrices comprising either a physical mixture of PEG, paraben, and PEO, or a solid solution of each paraben in PEG, incorporated in the PEO matrix. Considerable increase of the dissolution rate for the eutectic and in particular solid solution form of the parabens was observed. The hydration rate of all matrices, as well as polymer release, was the same. The release rate of methyl, ethyl, and butyl parabens in solid solution form was similar to that of their crystalline form. However, the release rate of the solid solution form of propyl paraben was higher than that of its crystalline form, especially in the initial part of the release. The results indicate that all parabens crystallized in the gel layer of the solid solution formulations upon the process of tablet dissolution. This was proposed to be an effect of differences in the dissolution and crystallization kinetics of the parabens.
Tajarobi
Farhad
F
AstraZeneca R&D, SE-431 83 Mölndal, Sweden. farhad@chalmers.se
Abrahmsén-Alami
Susanna
S
Larsson
Anette
A
D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003692:Delayed-Action Preparations / Q000032:analysis / Q000737:chemistry; D005079:Excipients / Q000032:analysis / Q000737:chemistry*; D005782:Gels; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D010226:Parabens / Q000032:analysis / Q000737:chemistry*; D010592:Pharmaceutic Aids / Q000032:analysis / Q000737:chemistry*; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000032:analysis / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions; D013607:Tablets; D014867:Water / Q000032:analysis
D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D010226:Parabens; D010592:Pharmaceutic Aids; D013535:Suspensions; D013607:Tablets; D014867:Water; D011092:Polyethylene Glycols