Molded Tablets And Solid Dispersions Based On Photopolymerization

Molded tablets are the earliest tablets used by humans with simple preparation processes.However,compared with modern mechanized compressed tablets,the preparation efficiency is low,the tablet hardness is small,and the quality is difficult to control,resulting in little application and little research.In this paper,the mechanism of rapid photopolymerization of N-vinyl-2-pyrrolidone?NVP?to produce polyvinylpyrrolidone?PVP?under ultraviolet light irradiation is adopted.NVP,photopolymerization initiator,and drug powder are mixed into a soft material,and then 3D printing technology prepares various types of molds,prepares various types of mold printing tablets,and examines the mold morphology and tablet properties in detail.In addition,the mechanism by which NVP can dissolve part of the drug is still used to obtain a solid dispersion by photopolymerization.As a method different from the traditional solid dispersion process,this article conducted a detailed investigation of the compatibility of the drug and NVP and its mechanism,the nature of the solid dispersion.1.Ibuprofen molded tablets based on photopolymerization and 3D printed moldsScreening of two 3D printing molds,fused deposition method?FDM?and light curing method?SLA?,scanning electron microscope showed that the surface of the mold printed by SLA was smoother than that of FDM.Use SLA to print molds of various shapes,use ibuprofen as a model drug,mix the NVPsolution containing photoinitiator with ibuprofen,and then pour the mixture into the mold.After molding,use a 365 nm UV lamp irradiation can obtain high-loaded ibuprofen molded tablets.The content of NVPsolution in the ibuprofen molded tablets is 7%?w/w?.The appearance of the molded tablets shows that the surface is flat and the overall structure is intact.The hardness of the round tablet is 3-4 kg.Scanning electron microscopy showed that the ibuprofen API was irregularly distributed in the molded tablets.The PVP was distributed in an irregular network structure inside the molded tablets and the API was tightly wrapped.This structure enhanced the hardness of the tablet.Compared with the in vitro release of marketed ibuprofen drugs,the ibuprofen molded tablets showed a slow-release effect,the longest release time reached 345 min,and the dissolution curves of all ibuprofen molded tablets conformed to the Ritger-Peppas equation.The drug release amount exceeds 90%,and the drug release rate is maintained at 0.2 mg/min-0.5mg/min.The HPLC detection of NVP residues in ibuprofen stencils of different specifications after heattreatment were 0.02 wt%,0.01 wt%,0.02 wt% and 0.07 wt%.2.Drug solid dispersion based on photopolymerizationA solid dispersion is prepared by photopolymerization,the NVP solution containing the photoinitiator is dissolved in the drug,and the above solution is irradiated with a 365 nm ultraviolet lamp,and the solid dispersion is obtained after the solution is solidified.Some drugs have a certain anti-free radical effect and show concentration dependence.The absorbance of DPPH absolute ethanol solution added with the above drugs is less than?<0.557?that of the same concentration DPPH absolute ethanol solution without drugs.However,the absorbance of DPPH absolute ethanol solution without anti-free radical drugs is almost the same as??0.693?that of DPPH absolute ethanol solution without drug addition.Anti-free radical drugs can stop the photopolymerization reaction and cause NVP to not cure.The ESR spectrum shows that the signal strength of DPPH absolute ethanol solution with anti-free radical drugs is much lower than that of the control group?<29.43×10⁴?.After analyzing the compatibility of drugs and NVP,artesunate and ibuprofen were selected as model drugs to prepare solid dispersions.In vitro release indicates that when the prescription is the same,the solid dispersion prepared by the photocuring method has a better dissolution effect than the traditional method,which increases the solubility of the drug.Fourier infrared spectroscopy shows that the stretching vibration peak of the functional group of the drug in the solid dispersion has shifted.The ibuprofen API has a carbonyl stretching vibration peak at 1707.57 cm^-1,while the carbonyl stretching vibration peak in the ibuprofen solid dispersion becomes 1668.64 cm^-1;the artesunate drug substance had a stretching vibration peak of hydroxyl group at 3270.51 cm^-1,but no absorption peak was observed at the same position of the artesunate solid dispersion.Ibuprofen has a strong characteristic diffraction peak of drug crystals at 2? = 6.058 °and other positions,and artesunate has a strong characteristic diffraction peak of drug crystals at 2? = 9.425 °and other positions,however,the characteristic peaks did not appear in the solid dispersion prepared by the two drugs.Ibuprofen has an endothermic peak at 80 ?,artesunate has an endothermic peak at 150 ?,and no absorption peak is observed in the solid dispersion,indicating that the drug is in an amorphous form in the solid dispersion presence.This paper makes full use of the properties of NVP to prepare different shapes of molded tablets with high hardness,small volume and large drug loading,which overcomes the problems of low hardness andless style of traditional die-printed tablets;at the same time,the preparation of drug solid dispersions based on the photopolymerization properties of NVP can increase the dissolution of poorly soluble drugs and have a controlled release effect.