Preparation Of Drug-loaded Fiber Films And Granules Via Melt Centrifugal Technology

Melt centrifugation is a solvent-free,high-throughput preparation technology,during which melts were stretched into fibers or further broken into granules by centrifugal force.It has a good industrial application prospect in the preparation of fibrious film and granule.In this study,common active ingredients and pharmaceutical excipients were used to prepare drug-loaded fiber films and granules via melt centrifugation technique,and the fiber and granule formability mechanism was also studied.The results could contribute the promotion and application of melt centrifugation technology in the field of pharmaceutical preparations.Five common active ingredients were used to investigate their fiber formability and the immediate release properties.The results showed that indomethacin and nifedipine could form fibers during melt centrifugal spinning(CMS)process.The melt rheology curve of the fiber-forming drugs were relatively flat,therefore the melt viscosity was kept moderate throughout the CMS process,and the melt could be stretched into fibers by centrifugal force.In vitro dissolution study showed that pure drug fibrous films composed of poorly soluble drugs had a good immediate release performance(cumulative drug release at 10 min was 95.8%and 93.9%for indomethacin and nifedipine,respectively).It may be related to the large specific surface area of the fiber film and the significant decreased crystallinity of drugs during the CMS.Six pharmaceutical excipients were used to study the fiber formability and release properties.The results showed that Eudragit~?EPO,Soluplus~?,Eudragit~?RL,Eudragit~?RS and ethylcellulose formed fibers during melt centrifugal spinning(CMS)process.The melt rheology curve of fiber-forming excipients were relatively flat,which facilitated the fiber formability via melt streching during the CMS process.The type and amount of plasticizer have significant effect on the operating temperature,fiber diameter,yield and appearance of the fibrous film.In vitro dissolution study showed that indomethacin loaded fiber film using Soluplus~?as a hydrophilic carrier had good immediate release properties(cumulative drug release at 5 min 90.0%).While indomethacin loaded fibrous film using Eudragit~?RL as a hydrophobic carrier had 12 h sustained release property.Further addition of polyethylene glycol as a pore formation excipient increased the drug release extent(cumulative drug release at 12 h increased from 45.3%to 72.4%).A two-dimensional plan projection model of the CMS flow field was established.Using indomethacin and plasticized Eudragit~?RL as typical active ingredient and excipient,the steady-state finite element simulation of the CMS flow field was conducted.The simulation results showed that the total pressure,turbulent energy and velocity of indomethacin and plasticized Eudragit~?RL were axisymmetric in the overall flow field.Centrifugal force and pore morphology had more influence on the flow field simulated results of plasticized Eudragit~?RL with high viscosity than that of indomethacin with low viscosity.Based on the fluid dynamics simulation,the influence of rotation angle and outlet velocity of fiber was further studied.An increase in the rotational speed,a decrease in the inlet velocity,or a decrease in the melt viscosity resulted in an enlarged rotation angle of the fiber trajectory.A decrease in inlet velocity,an increase in collection radius,or an increase in melt viscosity resulted in decreased outlet velocity of fiber.The position and speed at which the fiber reaches the collector could be adjusted by various operation parameters(rotation speed and inlet speed)and various collectors of different radii.Five active ingredients and eight pharmaceutical excipients were used to study the granule formability,hygroscopicity and immediate release properties.The results showed that tinidazole,metoprolol tartrate,indomethacin,nifedipine,polyethylene glycol,mannitol,stearic acid,glyceryl monostearate and paraffin formed granules during melt centrifugal atomization(MCA).A low viscosity over a wide temperature range facilitated granule formation,because melt jet with low viscosity could break into droplet under the action of centrifugal force.Astragalus polysaccharide was used as a typical hygroscopic ingredient to investigate the anti-hygroscopicity of MCA granules.The moisture absorption rate at 24 h of MCA granules(6.49%)was significantly lower than that of physical mixture(9.80%)and pure astragalus polysaccharide(13.51%).Indomethacin and nifedipine were used as typical poorly soluble drugs to evaluate the immediate release properties of MCA granules.In vitro dissolution results showed that pure indomethacin MCA granules had a good immediate release performance(cumulative drug release at 5 min was 93.5%).Nifedipine-polyethylene glycol MCA granules have a good immediate release property.With a drug-excipient ratio of 1:4,the cumulative drug release at 10 min was93.5%.It could be explained by the highly dispersed drug in the form of amorphous into the carrier.