Evaluation of floating and sticking extended release delivery systems: an unconventional dissolution test.
The extent to which hydrophilic matrix tablets with a propensity to stick to the dissolution apparatus and/or float are susceptible to variations in hydrodynamic conditions during dissolution testing was investigated. Furthermore the usefulness of simple alternatives to the current compendial tests is examined. Swellable hydrocolloid (guar) matrix tablets containing verapamil HCl were evaluated using USP dissolution apparatus I and II. Two additional configurations where an additional single ring and mesh device or a double mesh device was located below the paddle in the dissolution vessel were also evaluated. Tablets were placed on top of the single mesh device or in the compartment formed by the two mesh surfaces of the double mesh device. In all cases near linear (n>/=0.82) release profiles were observed. When using apparatus I it was observed that the highly swellable tablets were fully constricted by the basket within 5-7 h. This prevented further independent movement and unimpeded swelling and coincided with a departure from linear release and increased variability (S.D.</=9.5%). Under standard apparatus II conditions two out of three tablets adhered to the bottom of the dissolution vessel for the duration of the experiment. Consequently their release profiles differed markedly from those obtained under apparatus I conditions (similarity factor, f(2)=30.5) with the release rate being approximately half of that obtained under apparatus I conditions. Adhesion to the dissolution vessel was also observed when paddle speed was doubled to 100 rpm, thus again resulting in large variability (S.D.</=34%). Whilst the averaged single and double mesh configuration profiles were similar to the apparatus I profile (f(2)=57.36 and 61.38, respectively), large variability (S.D.</=11%) occurred with the single mesh configuration due to floating and random adhesion of tablets to the paddle or sampling tubes. Almost superimposable profiles were obtained for the individual tablets (S.D.<3%) when the tablets were located in the compartment formed by the double mesh device. Use of a double mesh device may therefore provide an alternative to current compendial dissolution methods when the reliable determination of the true release kinetics of floating and sticking delivery systems is desired.
Dürig
T
T
Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Fassihi
R
R
D000268:Adhesiveness; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation*; D003692:Delayed-Action Preparations; D005685:Galactans; D007700:Kinetics; D008351:Mannans; D053149:Plant Gums; D012995:Solubility; D014700:Verapamil / Q000008:administration & dosage / Q000737:chemistry
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D014700:Verapamil; C007894:guar gum