2.6.3. In vitro drug release study

For CLOP, in vitro drug release studies were carried out in 750 ml of 0.1 N HCL for 2 hrs. For APX, in vitro, drug release studies were carried out in 900 ml of 0.05 M Sodium phosphate buffer with 0.05 % SLS for 24 hrs. A USP type II dissolution apparatus (paddle type) was used to test both at 75 rpm and 37 ± 0.5 °C. All dissolution studies were performed on three tablets of each formula.

The in vitro drug release study for the final FDC, two strengths, was carried out using the USP delayed release method A (United States Pharmacopeial Convention, 2011). The study was performed in 750 ml of 0.1 N HCL. Samples were withdrawn at (5, 10, 20, 30, 45, 60, and 120 min.). After 2 hrs., 250 ml of 0.2 M tribasic sodium phosphate equilibrate 37 ± 0.5 °C was added to the dissolution media, and the pH of the media was adjusted to (6.8 ± 0.05). The apparatus continued to run for 24 hrs. A sample of 5 ml was withdrawn from the dissolution media in a specified period (4, 8, 12, 16, 20, and 24 hrs.). All of the experiments were tested using a USP type II dissolution apparatus (paddle type) at 75 rpm and 37 ± 0.5 °C. All dissolution studies were performed on six tablets of each formula.

A sample of 5 ml was withdrawn from the dissolution media using an auto-sampler, and no volume correction was made. The samples were filtered using a 0.45 μm Clarify® syringe filter. The absorbance of the samples was measured using a spectrophotometric method at 210 nm using HPLC developed method(Al-Shami et al., 2024) and the % cumulative release (% CR) was plotted using calculated mean values of cumulative drug release versus time.

The release data were fitted to five kinetic models including; zero-order, first-order, Higuchi, Hixon-Crowell, and Korsmeyer-Peppas to determine the drug release mechanism with the aid of DD Solver add-in software. The drug release mechanism was considered according to the coefficient of determination; R² values (Grassi and Grassi, 2014).