Many newly discovered active pharmaceutical ingredients (API) are poorly water-soluble, which can be a challenging in the development of oral dosage forms. One of the approaches to improve solubility is the formation of self-microemulsifying drug delivery systems (SMEDDS). SMEDDS are a mixture of lipids, with solubilized API, cosolvents and surfactants. Stable oil-in-water microemulsion is formed spontaneously upon dilution with aqueous media and gentle stirring. SMEEDDS are liquid formations, therefore they have lower stability and more expensive production. The solution are solid SMEDDS, which are made from liquid SMEDDS by various solidification methods.
The purpose of our research work was the transformation of liquid SMEDDS (with carvedilol as a poorly water-soluble model drug) into a solid form by wet granulation and successfully compressing the produced granules into a tablet. Carriers of different porosity (Aeroperl® 300, Avicel® PH-101, Fujicalin® SG, Neusilin® US2, Syloid® 244FP, Syloid® XDP 3050) were used for granulation by hand. In the produced granules, SMEDDS represented 35-66 % of the weight. The produced granules were evaluated by various methods. All granules had good flow properties. We confirmed the preservation of self-microemulsifying properties and proved faster release of carvedilol from ganules than dissolving crystalline carvedilol.
Based on the results of the granules evaluation, the two best carriers (Neusilin® US2, Syloid® 244FP) were selected and granulated in a high shear granulator. In order to compare manual and machine production methods the produced granules were evaluated by the same methods as hand-made granules. The assumption that the granules made in high shear granulator have smoother surface and more spherical shape was confirmed by scanning electron microscopy, resulting in improved flow properties.
Finally, a self-microemulsifying tablet weighing 845 mg with a 12.5 mg dose of carvedilol was compressed with the addition of excipients. The produced tablets met the pharmacopoeial criteria of disintegration (<51 s) and friability (<0.22 %). In the dissolution test, due to the collapse of the porous structure of the carrier, API release rate was slightly slower than from the granules.