Pellets

Lipid and surfactant excipients have been used to prepare self-emulsifying pellets that are suitable for direct filling into hard gelatin capsules or for preparing tablets by direct compression. Franceschinis et al. (63) produced self-emulsifying pellets with improved drug dissolution and enhanced permeability of the model drug, nimesulide, by wet granulation with microcrystalline cellulose, lactose, mono-, and diglycerides and polysorbate 80. In another study, a self-emulsifying pellet formulation of progesterone was prepared by extrusion and spheronization (64). A 50:50 mixture of oil (mono- and diglycerides) and polysorbate 80 was prepared by melting the glycerides at 50°C, adding the surfactant, and cooling the mixture to room temperature, yielding a liquid in which the progesterone was dissolved. The solution was combined with microcrystalline cellulose and small amounts of water and ethanol, resulting in solidified mass that was extruded, spheronized and filled into hard gelatin capsules. A three-way randomized crossover study was conducted in beagle dogs comparing progesterone bioavailability from hard gelatin capsules containing the extruded pellets, the liquid formulation (pre-extrusion), and an aqueous suspension. At a constant dose of 16 mg, the area under the curve (AUC) and maximum plasma concentration (Cmax) of the extruded pellets and the liquid formulations were both found to be seven- to nine-fold higher than those of the aqueous suspension, clearly demonstrating that the bioavailability-enhancing properties of the liquid formulation were not lost following conversion to an extruded semi-solid formulation capable of being dry-filled into capsules or compressed into tablets.

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