Effect of formulation parameters and drug-polymer interactions on drug release from starch acetate matrix tablets.
The aim of this study was to determine, whether interactions between a drug and hydrophobic polymer matrix are present, and if so, how they affect the drug release. In addition, the most important formulation parameters, for example porosity or structure of the tablet, which have the greatest impact on drug release, were defined. Six different drug compounds, that is allopurinol, acyclovir, metronidazole, paracetamol, salicylamide and theophylline, were used in different formulations with hydrophobic starch acetate (DS 2.7) as a matrix forming polymer. Results indicate that the formulation parameters describing directly or indirectly the structure of the matrix, such as porosity, compaction force and the particle size fraction of the filler-binder, have the strongest impact on drug release. The contribution of drug property based variables is not as high as formulation parameters, but they cannot be overlooked. The contribution of water solubility and dissolution rate of the compound are obvious, but there are other significant parameters, which describe the hydrophobic and hydrophilic regions of the molecule, that also affect the drug release. This can be seen especially with the salicylamide: compound which appears to have a strong and sufficiently high hydrophobic region that interacts with starch acetate and impairs the drug release.
Pajander
Jari
J
Department of Pharmaceutics, University of Kuopio, FI-70211 Kuopio, Finland. pajander@hytti.uku.fi
Korhonen
Ossi
O
Laamanen
Maria
M
Ryynänen
Eeva-Leena
EL
Grimsey
Ian
I
van Veen
Bert
B
Ketolainen
Jarkko
J
D000107:Acetylation; D000704:Analysis of Variance; D002240:Carbohydrate Sequence; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D005079:Excipients; D016018:Least-Squares Analysis; D008969:Molecular Sequence Data; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D013213:Starch / Q000031:analogs & derivatives* / Q000737:chemistry; D013607:Tablets
D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers; D013607:Tablets; D013213:Starch; C050766:starch acetate