Tablet and capsule hydrophilic matrices based on heterodisperse polysaccharides having porosity-independent in vitro release profiles.
The purpose of the study was to investigate the release-controlling action of a swellable hydrophilic material based on heterodisperse polysaccharides (HP) in relation to the initial pore structure of the formulations. HP-based granules were produced under carefully controlled conditions and compacted into matrix tablets having equivalent tablet thickness. Quantification of pore structure using mercury porosimetry showed that the tablets had substantially different pore volumes and pore size distributions. Dissolution studies demonstrated that release of a water-soluble model compound, benzamide, from swollen matrices was affected neither by total porosity nor median pore diameter of the initial dry matrix. To extend the concept of porosity-independent release further, HP-based formulations containing either diclofenac sodium or propranolol HCl were contained within hard gelatin capsules in the form of uncompacted granules. This produced a dosage form with a high intraparticulate porosity in the dry state. Equivalent weights of the same formulations were also compacted into tablets. The in vitro release profiles from matrix tablets compacted from any of the formulations did not differ significantly from release profiles obtained when the same materials were contained uncompacted in hard gelatin capsules.
Kelly
M L
ML
Department of Pharmacy and Pharmacology, University of Bath, U.K.
Tobyn
M J
MJ
Staniforth
J N
JN
D001549:Benzamides / Q000493:pharmacokinetics; D002214:Capsules / Q000138:chemical synthesis*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008628:Mercury / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D016062:Porosity; D011433:Propranolol / Q000493:pharmacokinetics; D012995:Solubility; D013607:Tablets / Q000138:chemical synthesis*; D013997:Time Factors
D001549:Benzamides; D002214:Capsules; D003692:Delayed-Action Preparations; D011134:Polysaccharides; D013607:Tablets; D004008:Diclofenac; C037689:benzamide; D011433:Propranolol; D008628:Mercury