Purpose: Self-Emulsifying Drug Delivery Systems (SEEDS) have been widely explored as alternative nanoplatforms to improve drug dissolution rate and permeability, thus increasing the bioavailability of BCS class II and IV drugs. However, the anhydrous liquid forms of the SEDDS have been associated with reduced stability and increased manufacturing costs, justifying the attempts to transform these systems into solid dosage forms. In this sense, we explored the tableting performance and product quality attributes of solid SEDDS containing quercetin as a model drug that were prepared using ten commercially available porous excipients (Neusilin® US2/UFL2, Zeopharm® 600, Aeroperl® 300, Aerosil® 200/300, RxCIPIENTS® GL100/200, Syloid® XDP3050/3150).
Methods: Formulations were prepared by physically mixing the standard quercetin-containing SEDDS formulation with different porous excipients to obtain the powdered solid SEDDS. Pre-tableting compression studies were performed using a tensile tester by uniaxially compressing the formulations in a cylindrical fixture. Tableting studies were performed on an eccentric press under constant tensile strength. Products were assessed for physical and chemical stability, disintegration and quercetin dissolution.
Results: All excipients showed both elastic and plastic components on their strain-stress curves. Maximum compressive strains were slightly reduced upon adsorption of SEDDS when compared to the pure excipients, which is related to the overall increase in bulk density. Elastic recovery was reduced after SEDDS adsorption as well, especially for Aeroperl® 300 and Aerosil® 200/300 (around 2-fold reduction). The change in elastic recovery is due to a binding-like effect of the lipid formulation, and it is remarkable as it makes the manufacture of SEDDS tablets with those excipients feasible when compared to the pure porous excipients. Pilot tableting was performed and all formulations yielded tablets with adequate physical properties (hardness, friability, weight variation) at a targeted tensile strength of 0.6 MPa, except for RxCIPIENTS® GL100/200 that did not form tablets. In vitro disintegration and dissolution studies showed that SEDDS tablets did not disintegrate, demonstrating the necessity of additional excipients. Crospovidone (5% w/w) was added to tablet formulations which allowed the manufacture of fully functional S-SEDDS tablets.
Conclusion: We demonstrated the tableting compactability of solid SEDDS prepared with direct mixing of porous pharmaceutical excipients with SEDDS. However, for the manufacture of fully functional tablets, the addition of super-disintegrants to the formulations is highly recommended to enhance disintegration/dissolution performance.