Hotmelt Extrusion For Preparation Of Nifedipine Controlled Release Tablet

The preparation of Nifedipine solid dispersion by hot-melt extrusion was study and the dissolution of solid dispersions which are with different extrusion materials and in different media in vitro was investigated. In addition, the dissolution in vitro and pharmacokinetic in Beagle dogs was also studied after suppressing, ultimately confirm the preparation technology which is similar to adalat.Objective:As the calcium antagonists of dihydropyridine which used for clinical purposes firstly, Nifedipine can be used for hypertension and angina pectoris. The controlled-release tablet of Nifedipine could keep the balance of blood concentration, reduce the administration times and increase the compliance of patient. Although adalat which distributed in market has better effect than other drugs because of its osmotic pump principle, preparation process was complex and difficult. So the hot melt extrusion technology for the preparation of solid dispersions can be used to improving the solubility of sparingly soluble drugs and facilitate industrialized production. The purpose of the study is to prepare the Nifedipine controlled release tablet with the similar functions of adalat through the technology combining with the skeleton material, and easy for industrialized production.Method:①Study on pre-formulation. To set up the UV spectrophotometric method measuring Nifedipine, investigate drug and carriers at the different conditions of physical and chemical properties, and establish the method of Nifedipine dissolution in vitro.②To prepare Nifedipine solid dispersions by hot melt extrusion technique. As carriers, the H-HPC, HPMCAS, PVP-VA64and acrylic resin IVwere used to prepare the Nifedipine solid dispersions by hot melt extrusion technique. And investigate its dissolutions in different solvent including purified water, pH1.0hydrochloric acid solution, pH4.5acetic acid solution and pH6.8phosphate citrate buffer salt, and the same as dissolution medium which adds1%SDS.③The preparation of controlled release tablet of the Nifedipine solid dispersions. To press the tablets with the specification of300mg tablet containing30mg activity component and investigate the dissolution in vitro in which that1%SDS in the phosphate citrate salt buffer solution, in order to select the skeleton and its dosage. Then make use of F2similarity factor method to determine what kind of suppression in vivo pharmacokinetic analysis.④To determine the bioavailability of adalat and nifedipine solid dispersion tablet and nifedipine drug tablet in Beagle dogs. To establish the HPLC method to detect nifedipine plasma concentration, and homemade nifedipine controlled release tablet and nifedipine drug tablet and adalat was used to carry pharmacokinetic experiments in Beagle dogs at the same time, to compare the similarities and differences between them.Result:①To establish the UV spectrophotometric method to determine the dissolution of Nifedipine in vitro, which is simple, feasible and convenient to operation.. Not only the physical and chemical properties of different carriers of Nifedipine but also the operating technology of hot melt extrusion were confirmed.②As carriers, the H-HPC, HPMCAS, PVP-VA64and acrylic resin Ⅳ were be used to prepare the Nifedipine solid dispersions by hot melt extrusion technology. It was indicated that the solid dispersions could improve the dissolution of Nifedipine through investigating various solid dispersions in all kinds of dissolution medium, just because of different medium with different degree. The carrier material we end use is need further options by compressed tablets and evaluate their dissolution in vitro.③It confirmed that the tablets need to be prepared with HPMCAS as carrier and HPMC K4M45%as skeleton material. By investigating, the tablets which were prepared with HPMCAS as carrier and HPMC K4M45%as skeleton material were compared with Adalats to carry pharmacokinetic experiments in Beagle dogs, and with common Nifedipine drug tablet.④This HPLC analysis method was is specific, sensitive, reproducible and easy to process. It shows that both Tmax, Cmax, and AUC are similar, relative bioavailability is108.1%, but compared with adalat, the plasma concentration of homemade tablets have obvious differences between individuals. Compared with Adalat, Nifedipine drug tablet has no similar bioavailability.Conclution:Solid dispersions which prepared by hot-melt extrusion could improve the solubility of Nifedipine. HPMCAS was used as carrier and HPMC K4M45%as skeleton material to prepare the controlled release tablets which have the similar dissolution and in vitro pharmacokinetic data like adalat. And the method is easy to process. But further investigates should be developed in order to prepare the more stable controlled release preparation.