Amorphous Nanoparticles Enhance Oral Absorption Of Felodipine

At present,a considerable part of the pharmaceutical ingredients under development are water-insoluble drugs,which belong to BCS Class II or Class IV.Poor water solubility of these compounds is the main reason for the low bioavailability of the preparations.Therefore,it is important to develop formulations that can increase the solubility or bioavailability of such compounds.Nanoparticles?NPs?had proven to be one of the effective means to improve solubility,dissolution rate and bioavailability.The anti-solvent precipitation method is a classic method that can efficiently prepare nanoparticles.This method does not consume a lot of energy input,and the preparation process is efficient and fast.Polymer pharmaceutical excipients are a type of polymer excipients with good biocompatibility and safety,which applied to pharmaceutical preparations.They have various types and functions,and can be used as stabilizers,thickeners,adhesives,disintegrating agents,sustained and controlled release excipients and coating materials are widely used in the pharmaceutical preparation industry.The purpose of this study was to select the poorly water-soluble drug felodipine as a model drug,to screen polymer medicinal excipients that can be used to prepare quick-release nanoparticles by anti-solvent precipitation method,and to study the pharmacokinetic behavior of nanoparticles,and to explore the mechanism of action of polymer excipients on the stability and molding of nanoparticles.Felodipine-HPMC AS_MF quick-release nanoparticles were prepared by anti-solvent precipitation method to study the particle size,dissolution,DSC,morphology and pharmacokinetic behavior of the nanoparticles.The results showed that nanoparticles had a particle size of 390.8±28.8 nm,a Zeta potential of–25.5±0.7 m V.And could not be released at p H 1.2 HCl,the cumulative release in 2 hours at p H 6.80PBS was about 80%,and could be released completely in 5 minutes in the release medium containing 0.05%and 0.3%SDS p H 6.80 PBS.The DSC results showed that the prepared nanoparticles are amorphous,and the nanoparticles are spherical under TEM field of view.Felodipine amorphous nanoparticles reach a peak at 0.8 h after oral administration,and the peak time is significantly shorter than that of micelles and APIs,which is about 0.22 times that of micelles and 0.4 times that of APIs;the maximum plasma concentration is higher than that of felodipine micelles.It is 2.6 times that of micelles and 16.5 times that of APIs,indicating that felodipine amorphous nanoparticles can be quickly absorbed into the blood in the intestine;the blood drug concentration drops rapidly after an hour,and it is always at a lower blood drug concentration since then,the reason may be the recrystallization of nanoparticles in the gastrointestinal tract and the absorption rate slows down.The bioavailability at 6 h is about 1.1 times that of the felodipine micelle group and 11 times that of the felodipine API group.The plasma concentration of felodipine micelle group remained at 1.8?g/m L after administration,and the cumulative bioavailability was higher than that in the felodipine nanoparticle group.In addition,dissipative dynamics simulation?DPD?is also used to study the mechanism of nanoparticle molding.It was found that the stabilizer HPMC ASMF adsorbed on the surface of nanoparticles to form core-shell nanoparticles.As the drug loading ratio increased,holes appeared in the shell and increased with the increase of drug loading ratio.