## 3 Results and Discussion
### Influence of Formulation Factors on the In Vitro Availability of Felodipine in Experimental Tablets
At two hours, the felodipine dissolution in 1% LSNa medium was 15.70% for F7, which contained 38.00% HPMC E10 and 12.00% HPMC K100, higher than the percentage of 8.35% felodipine dissolved from the reference formula. For F7, the dynamics of the active ingredient release were faster in the first 6 h, but after 12 h the percentage of dissolved felodipine was only 44.16%, in comparison with 87.08% for the reference formula. F7 showed a reduction in felodipine release at 12 h on 0.1% LSNa medium, but no changes in the 0.4% CTAB medium were detected. When analysing the similarity, \(f_{1}\), and difference, \(f_{2}\), factors, the results for the reference formulation resemble F4 in 0.4% CTAB medium, but contrast in 1% LSNa medium. In this case, in the two different media, the dissolution behaviour showed important differences between the experimental formulation profiles and the slower release reference product (Table 11b). The association of water-soluble matrix-forming polymer E50 with a medium viscosity HPMC K100 increased felodipine release compared to the formulation containing only 30% HPMC K100 polymer (F2). Dissolution in 1% LSNa medium for F8 was 13.2% at 2 h and 74.4% at 12 h. For F9, the percentage of felodipine dissolved was 13.4% at 2 h and 94.7% at 12 h [38; 39]. Considering the difference and similarity factors, F8 and F9 profiles were close to the reference formulation in LSNa 1%. On 0.4% CTAB medium, F9 presented dissolution profiles very much like the reference, with a 14.55 difference factor and a 58.74 similarity factor. The highest correlation degree was presented by F8, with values of 11.57 for \(f_{1}\) and 62.91 for \(f_{2}\). The optimum ratio of the matrix was displayed by F9, consisting of two types of HPMC mixture, 35% high viscosity and 65% medium viscosity hydrophilic polymer, representing a total proportion of 42.5% of the total formulation mass. When two HPMC polymers were combined in the formulation, it was found that the presence of a larger proportion of higher-polymerization-degree or -viscosity polymer led to a decrease in the felodipine release rate. Release in the higher-surfactant-content dissolution media led to an increase in the released amount, respecting the above particularity [40; 41; 42]. The release was lower in CTAB than in LSNa medium. _Influence of the active ingredient granulometry on the dissolution profile_  
In 1% LSNa medium, the relodipine release from F10 was 12.9% at 2 h and 85.3% at 12 h. For F11 manufactured using microcrystalline relodipine, the relodipine dissolution was 42.2% at 2 h and 98.4% at 12 h. In CTAB, F10 showed percentages of 7.2% relodipine dissolved at 2 h and 60.5% relodipine dissolved at 12 h, while F11 released 4.7% percent of relodipine at 2 h and only 47.3% at 12 h (Figure 10). The correlation degree of the dissolution profiles was determined by the difference factor and similarity factor (Table 12), with values of 49.86 for \(f_{1}\) and 32.16 for \(f_{2}\) in LSNa medium. Meanwhile,\(f_{1}\) was 20.05, and \(f_{2}\) was 57.61 in CTAB medium. In 1% LSNa medium, the relodipine dissolution differed significantly between F10 and F11, but in CTAB medium, the dissolution profiles for experimental formulations containing macrocrystalline (F10) and microcrystalline (F11) relodipine showed similarity factors of more than 50. Figure 10 shows the dissolution curves of the two formulations containing relodipine in two different particle sizes, in the two different surfactants dissolution media. The relodipine release from tablets containing the microcrystalline form was complete at 12 h in 1% LSNa medium, while from the macrocrystalline-form tablets, it was only 85%. In a 0.4% CTAB surfactant dissolution medium, the relodipine release rate from tablets with macrocrystalline particles was slightly slower than that from microcrystalline particle tablets, but it was much faster in the 1% LSNa medium.