Study On The Preparation Of Apigenin Nanosuspension By Cosolvent Technique

Purpose: Apigenin is a kind of flavonoids widely existing in nature,which has anti-tumor,anti-oxidation and anti-inflammatory effects.But because of its poor solubility and low bioavailability,it affects the clinical efficacy.In this study,the apigenin was prepared into a nanosuspension using the cosolvent technique.The optimal formulation and preparation process were optimized.The advantages of the apigenin nanosuspension in improving the solubility and release rate of apigenin were evaluated.LC/MS/MS method for content determination;exploring the advantages of apigenin nanosuspensions to lay a good theoretical and experimental basis for the development of such new drugs.Methods: The content of apigenin was determined by HPLC,and an in vitro analysis method was established.The preparation of Apigenin nanosuspension by cosolvent technique.The average particle size and polydispersity index(PDI)of apigenin nanosuspension were determined using a Malvern laser particle size analyzer;the star point design-response surface was used to optimize the formulation and preparation process of apigenin nanosuspension,and to verify the optimal Prescription;observe the morphology of apigenin nanocrystals with transmission electron microscopy and scanning electron microscopy;using X-ray powder injection,differential scanning calorimetry,and Fourier infrared spectroscopy to investigate whether the crystalline form of apigenin changes before and after nanocrystallization,and whether Interaction between stabilizers.The equilibrium solubility and in vitro release of apigenin original drug and nanosuspension were compared,and the nano-effects of apigenin nanosuspension in improving drug solubility and in vitro release rate were evaluated.Using silibinin as an internal standard,the plasma concentration of apigenin in SD rats after the administration of apigenin and nanosuspensions was measured by liquid chromatography-mass spectrometry to investigate its bioavailability.Results: The HPLC method for determination of apigenin nanosuspension was stable and accurate.The preparation of Apigenin nanosuspension by cosolvent technique.The single-factor test examined the factors such as the type and concentration of the latent solvent,the stabilizer,the initial concentration,the ratio of the solvent and the antisolvent,the dropping acceleration,the stirring speed,and the shear time.Solvent with sodium dodecyl sulfate(SDS)and povidone K30(PVP K30)combined stabilizer;Star point design-response surface method to select the best preparation process prescription: initial concentration 10 mg/ m L,Anti-solvent volume 160 m L(solvent: anti-solvent volume ratio 1: 8),SDS 160 mg(0.1%),PVP K30 320 mg(0.2%),good solvent phase injection rate 20.92 m L /min,water phase stirring rate 422 r/min,shearing time 15 min.The average particle size of 3 batches of nanosuspension prepared in parallel was(293.4 ± 4.9)nm and PDI was 0.076,indicating that the preparation process of apigenin nanosuspension was stable and the method had good reproducibility.According to the physical and chemical properties of the apigenin drug,excipients,physical mixtures,and apigenin nanocrystals,it was found that the apigenin nanocrystals were crystalline,regular in shape,and clear in structure.Apigenin nanosuspension has higher drug solubility and release rate than the original drug.Pharmacokinetic results show that the apigenin nanosuspension has a significantly higher bioavailability than the original drug.Conclusion: The subject has uniform particle size and good stability for the apigenin nanosuspension prepared by cosolvent technique.Compared with the original drug,its equilibrium solubility,in vitro release,and bioavailability were significantly improved.