| ObjectiveThe purpose of this study was to prepare a controlled release drug delivery system based on Hollow microcubes SnO2(HMSn)and push-pull osmotic pump tablet technology for improving the solubility and oral bioavailability of felodipine.MethodsIn this study,self-template method was used to synthesize HMSN by co-precipitation reaction.Felodipine was incorporated into HMSn by adsorption method to obtain HMSn-FDP.HMSn-FDP was characterized by various technologies such as TEM,DSC,FTIR.The solubilization ability of HMSn for FDP and The dissolution behavior of FDP of HMSn-FDP osmotic pump tablets were investigated by In vitro dissolution tests.The intestinal uptake of FITC-HMSn was visualized by CLSM.HMSN-FDP osmotic pump tablets were prepared by direct powder compression method.The optimal formulation of HMSN-FDP osmotic pump tablets were selected by single factor experiment with cumulative dissolution as the evaluation index.The quality of HMSN-FDP osmotic pump tablets were examined according to the quality requirements of tablets in the Pharmacopoeia(2020),The bioavailability of HMSN-FDP bilayer osmotic pump tablets were studied by the in vivo pharmacokinetic assay.ResultsHMSN were successfully prepared.DSC and FT-IR results showed that FDP was loaded in the hollow structure of HMSN with an amorphous state.The results of CLSM showed that HMSN could be rapidly absorbed by various segments of small intestine(duodenum,jejunum and ileum)after oral administration,which was more conducive to promoting the absorption of FDP.The optimal formulation of HMSN-FDP osmotic pump tablets:120 mg PEO(Mw 100,000)was used as a suspending agent and 80 mg PEO(Mw 6,000,000)was used as an expanding agent.60 mg NaCl was used as an Osmotic active substance.The core tablets were coated with CA as a semipermeable membrane containing PEG 4000 to control the membrane permeability.The weight gain of the coating is 10%of the core weight.The pore diameter of drug release was 8 mm.In vitro dissolution studies showed that HMSN-FDP osmotic pump tablets were able to deliver felodipine in an approximately zero-order manner in 12 h.And the quality test results of HMSN-FDP osmotic pump tablets were in compliance with the pharmacopoeia requirements.The drug release equation is:Q=6.308t-2.5037(r=0.9958)。The relative bioavailability of the HMSn-FDP osmotic pump tablets was 121.32±0.52%.ConclusionsHMSn can significantly improve the dissolution rate of the FDP,HMSn as drug carrier which associated with osmotic pump technology applications,HMSN-FDP osmotic pump tablets were able to effectively increase the bioavailability of felodipine and reduce fluctuations in its plasma concentration. |
