Abstract
Background: Cinacalcet HCl is a calcimimetic, BCS class IV drug with low oral bioavailability. Polymeric nanoparticles are widely used as biomaterials owing to their biocompatibility, biodegradability, varied structures, low toxicity, and simple and easy formulation process.
Objective: The aim of the study was to enhance the oral bioavailability of poorly water-soluble drug, i.e., cinacalcet HCl, by using a suitable particulate nanocarrier system, i.e., polymeric nanoparticles.
Methods: Biodegradable Cinacalcet HCl (CH)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by nanoprecipitation method using Poloxamer-188 as a stabilizer. The experimental parameters, like polymer concentration, stabilizer concentration, temperature, and RPM speed, were optimized. An optimized polymeric nanoparticle formulation PNP (F8) was solidified by adsorption on the porous carrier sylysia 350.
Results: PNP (F8) exhibited a particle size of 155 nm with low PDI (0.231) and high zeta potential (- 21.3 mV). In vitro diffusion study revealed sustained release of CH for 24 h for both PNP (F8) and solidified PNP (F8). Pharmacokinetics after oral administration of PNP (F8) and solidified PNP (F8) exhibited a 5-fold increase in bioavailability. Thus, both PNP (F8) and solidified PNP (F8) showed significant improvement in oral bioavailability.
Conclusion: Adsorption of polymeric nanoparticles onto porous carriers like sylysia 350 can be considered as a promising approach for long-term stability.
Keywords: Sylysia 350, nanoprecipitation, P-XRD, probe sonication, calcium-sensing receptor, cinacalcet HCl.
Graphical Abstract
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