Effect of standard and reversible arrangements of Ph.Eur./USP extraction cells during dissolution tests of calcium dobesilate in hydrogel formulation

Abstract

The aim of the study was to evaluate, in comparison to the reference product, the effect of the hydrophilic nonionic polymers: methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC), as well as the anionic polymers - copolymers of acrylic acid, on the release kinetics of a calcium dobesilate hydrogel formulation intended for application on the skin. In this work, we used an ointment cell for the release of the active pharmaceutical ingredient (API) from the formulations. This release was performed by employing the paddle method at 100 rpm, with the extraction cells placed in the release vessels in two different positions: with the semipermeable membrane faced to the top, or to the bottom of the vessel. Released API percentage was assessed via the validated spectrophotometric method. In the study with standard placement of the ointment cell, the release rates ranged from 4.45×10-3 min-1 for a formulation containing polyacrylic acid (PA), to 6.96 × 10-3 min-1 for a formulation based on HPMC. In the group of nonionic polymers, the release rate is higher in the case of HPMC, and lower in the case of MC. In the group of anionic polymers, the release rate is higher with the formulation of a modified copolymer of acrylic acid 11(PC11), while release from a formulation comprising a polymer PA is rather prolonged. We found that the placement of the extraction cell does not affect the alignment of the formulations investigated in terms of the release rates in the group of non-ionic formulations: HPMC > MC, and in the group of preparation of ionic polymers: PC11 > PA.