The oral osmotic oxybutynin release system (Oros), allowing once-daily administration, improves the oxybutynin tolerability over the immediate-release formulation. However, Oros manufacture requires a specialized technology. Therefore an attempt was made to design oxybutynin matrix tablets for once-daily administration in the treatment of urinary incontinence. Matrices (weight, 50 mg; diameter, 6 mm; dose, 5 mg) were prepared by compression, and the drug release kinetics in simulated gastric and intestinal fluids (SGF and SIF, respectively) were measured in vitro. Matrices intended to release the drug by diffusion were based on glycerol palmitostearate. This matrix type released the drug only in SGF. In SIF release stopped, due to the conversion, inside the matrix, of the freely water-soluble oxybutynin hydrochloride into the virtually insoluble free base form. Erodible matrices were based on Eudragit L100 (EUD L) or on poly(ethylene oxide) (PEO). Release in SIF from the former was either too slow or non-reproducible, depending on the EUD L fraction in matrix. Erosion-controlled oxybutynin release in SIF from matrices-based on PEO hydrogel was time-independent and depended on polymer MW and on dissolution medium hydrodynamics. A gastroprotected tablet based on a PEO of MW 5000 kDa released the dose in SIF at the rate of about 6%/h, appropriate for once-daily administration.
Design and in vitro evaluation of an extended-release matrix tablet for once-daily oral administration of oxybutynin
ZAMBITO, YLENIA;CARELLI, VERA;SERAFINI, MARIA FRANCESCA;DI COLO, GIACOMO
2005-01-01
Abstract
The oral osmotic oxybutynin release system (Oros), allowing once-daily administration, improves the oxybutynin tolerability over the immediate-release formulation. However, Oros manufacture requires a specialized technology. Therefore an attempt was made to design oxybutynin matrix tablets for once-daily administration in the treatment of urinary incontinence. Matrices (weight, 50 mg; diameter, 6 mm; dose, 5 mg) were prepared by compression, and the drug release kinetics in simulated gastric and intestinal fluids (SGF and SIF, respectively) were measured in vitro. Matrices intended to release the drug by diffusion were based on glycerol palmitostearate. This matrix type released the drug only in SGF. In SIF release stopped, due to the conversion, inside the matrix, of the freely water-soluble oxybutynin hydrochloride into the virtually insoluble free base form. Erodible matrices were based on Eudragit L100 (EUD L) or on poly(ethylene oxide) (PEO). Release in SIF from the former was either too slow or non-reproducible, depending on the EUD L fraction in matrix. Erosion-controlled oxybutynin release in SIF from matrices-based on PEO hydrogel was time-independent and depended on polymer MW and on dissolution medium hydrodynamics. A gastroprotected tablet based on a PEO of MW 5000 kDa released the dose in SIF at the rate of about 6%/h, appropriate for once-daily administration.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
