Influence of soluble and insoluble cyclodextrin polymers on drug release from hydroxypropyl methylcellulose tablets.
BACKGROUND
The influence of beta-cyclodextrin (beta-CD) polymers on drug release from hydroxypropyl methylcellulose (HPMC) matrices has not been reported in the literature.


OBJECTIVE
The influence of monomeric beta-CD and both soluble and insoluble beta-CD polymers on drug release from tablets containing either 30% or 50% hydroxypropyl methylcellulose has been studied using diflunisal (DF) as model drug.


METHODS
The DF-beta-CD inclusion complex (1:1 M) was prepared by coevaporation and characterised using X-ray diffraction, differential thermal analysis, and IR spectroscopy. The dissolution assays were performed according to the USP paddle method.


RESULTS
The incorporation of beta-CD in the complexed form increases drug release from hydroxypropyl methylcellulose tablets in comparison with the physical mixture because of the better solubilization of the drug. The soluble polymer promotes drug release to a higher extent than the physical mixture with monomeric beta-CD, but the insoluble polymer, which is itself a hydrogel, gives rise to the most retarded release profile, probably by retention of the drug in its structure. The formulations containing physical mixtures with either beta-CD or the soluble polymer present an optimum adjustment to zero-order release kinetics, and the inclusion complex followed non-Fickian diffusion according to the Korsmeyer-Peppas model.


CONCLUSIONS
The release profile of DF from a HPMC matrix can be modulated in different ways by the use of either monomeric or polymeric beta-CD.
Zugasti
Maria Esther
ME
Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
Zornoza
Arantza
A
Goñi
María Del Mar
Mdel M
Isasi
José Ramón
JR
Vélaz
Itziar
I
Martín
Carmen
C
Sánchez
Miguel
M
Martínez-Ohárriz
María Cristina
MC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004055:Differential Thermal Analysis; D004061:Diflunisal / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013607:Tablets; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D013607:Tablets; D047392:beta-Cyclodextrins; D065347:Hypromellose Derivatives; D004061:Diflunisal; D008747:Methylcellulose