Experimental factors affecting drug release from gel using VanKel (ENHANCER®) cells

Dissolution tests are quality control analyses routinely performed by pharmaceutical companies in order to assess the manufacturing process through the control of the reproducibility of the kinetic of the drug released from solid or semi-solid dosage forms. The European (8th Eu.Ph) and Italian Pharmacopoeia (FU XIII) report several dissolution test apparatus (type 1 to type 4) for different purposes, however some discrepancies remain about the use of the sample compartment for semi-solid dosage forms. VanKel Cell (Enhancer cell) is a PTFE volume–adjustable cell commonly used for in vitro release studies of semisolid formulations. However, even if this system has been widely used for research purpose in the last 20 years, a standardization of the method is still missing. The knowledge of the experimental factors influencing the dissolution test by using these cells is fundamental, especially in the case of their possible approval by the European Pharmacopoeia. Dissolution analyses were performed in a type-2 apparatus by using a 22% Poloxamer 407 gel, loaded with tramadol (25 mg/ml), as semi-solid formulation model. 2 g of the gel was placed inside a 4cm2 VanKel Cell mounting a membrane. Several parameters, as the position of gel loaded inside the cell, the speed and distance of the paddles from the cells and the thickness and the porosity of the membrane, have been investigated. Results from the dissolution experiments obtained at different conditions were analysed by calculating the dissolution efficiency (DE) and by fitting experimental data by the power law model. The statistical comparison revealed which are the most influencing parameters on the drug release from VanKel dissolution cells. A correct loading of the gel in the cell is fundamental in order to perform the release study. In addition, the thickness of the membrane and the speed of the paddles are important factors affecting drug release, contrarily to the distance of the paddle over cell compartment which was found not to influence the release profile. A slightly effect on the release profile was also observed with membranes at different porosity.