Functionalized calcium carbonate (FCC) as a novel carrier to solidify supersaturated self-nanoemulsifying drug...

Functionalized calcium carbonate (FCC), a novel pharmaceutical excipient, has shown promising properties in the field of oral drug delivery. The current study aimed at evaluating the feasibility of FCC as a carrier for the solidification of self-nanoemulsifying drug delivery systems (SNEDDS) containing the poorly water-soluble model drug carvedilol (CRV). Conventional, subsaturated SNEDDS (80 %-SNEDDS_liquid) and supersaturated SNEDDS (200 %-SNEDDS_liquid) were loaded onto FCC via physical adsorption at three ratios; 2.5:1, 3.0:1 and 3.5:1 (w/w) of FCC:SNEDDS_liquid, respectively, generating free-flowing powders (SNEDDS_FCC) with drug loading ranging from 0.8 % to 2.6 % (w/w) CRV. The emulsification of SNEDDS_FCC in a USP II dissolution setup (in purified water) was characterized using dynamic light scattering, resulting in similar droplet sizes and PDIs as observed for their liquid counterparts. The morphology and physical state of the obtained SNEDDS_FCC were characterized using scanning electron microscopy and differential scanning calorimetry. The physical stability and drug release upon dispersion were assessed as a function of storage time. The 200 %-SNEDDS_liquid were physically stable for 6 days, however, solidification using FCC stabilized the supersaturated concentrations of CRV for a test period of up to 10 weeks (solidification ratios 3.0:1 and 3.5:1 (FCC:SNEDDS_liquid)). SNEDDS_FCC achieved an improved rate and extent of drug release upon dispersion compared to the crystalline CRV in tap water (pH 7.5), however, to a lesser extent than their liquid counterparts. After 8 weeks of storage (25 °C at dry conditions), FCC was still able to rapidly release the SNEDDS_liquid and demonstrated the same rate and extent of drug release as freshly prepared samples. The solidification of 200 %-SNEDDS_liquid in presence of FCC greatly improved the drug loading and showed an enhanced drug release profile compared to the conventional systems. In conclusion, FCC showed potential as a carrier for solidification of SNEDDS and for the development of novel supersaturated solid SNEDDS for the oral delivery of poorly water-soluble drugs.