The Study Of Geometric Sustained Release Tablets Of Propranolol Hydrochloride

Sustained-release oral dosage forms have become one of the main directions in the research and development of oral preparations due to their advantages in therapeutics and economics.Compared with single layer matrix tablets,geometric tablets can adjust the release more flexibly and have become hot spot of present research.?-blockers are widely used in the treatment of cardiovascular diseases,such as heart failure,arrhythmia,hypertension and so on.Among them,propranolol hydrochloride(PPL)is the most widely used.We design it as geometric sustained release tablets to achieve zero order release in 24 hours,and explore the formability and release mechanism of geometric sustained release tablets.Firstly,effects of excipients on the water absorption,swelling and erosion rate of compressed hydrophilic matrix tablets were investigated.Water absorption and swelling rate of hydrophilic matrix tablets increase with the increase of the viscosity and amount of polymers.The results show that HPCGXF,MXF<HPMCK4M?HPCHXF<HPMCK15M,K100M<Carbomer<PEOWSR301,WSR303,40%<60%<80%<99%.Erosion rate decreases at the same time.Water absorption and swelling rate also increase with the increase of the solubility of fillers.The result of water absorption and swelling rate show that CaHPO4·2H2O=MCC<lactose<mannitol,and erosion rate decreases when using insoluble fillers,but they began to settle to the bottom of the cup at 0.5h.Secondly,the ratios of drug and barrier layers,the types and ratios of hydrophilic polymers,the types of release modifiers were studied.The formability and in vitro release of PPL hydrophilic geometric sustained release tablets were the main eveluatin indicators.When HPMCK4M is used as hydrophilic matrix,the ratios of three layers of 1.5:1:1.5 and 1.2:1:1.8 show the same release rates,but the latter has a better appearance.The formability and the release rate decrease with the ratios of hydrophilic polymers increase.The addition of release modifiers in drug layer has no effect on compression.The release rate decrease but followed afterwards by incomplete release.Finally,the amounts and types of lipids,the types of fillers were studied.We explore the formability and release mechanism of PPL hydrophilic-lipid geometric sustained release tablets by investigating the powder properties,the porosity of tablets,in vitro release,water diffusion and penetration rate of release process,water adsorption,swelling and erosion rate,the gel thickness and strength,etc.Then,the hydrophilic-lipid-filler system was studied.The formability and in vitro release of geometric sustained release tablets were the main eveluatin indicators.The results show that the addition of lipids reduces the compressibility and formability of the powder.After tabletting,the porosity is lower.When the amount of lipid in drug layer increased from 0%to 10%-30%,the release rate of 0-12h decreased slightly,and the release rate decreased with the increase of the amount of lipid in barrier layer from 0%to 30%.The water absorption,swelling and erosion rate of the tablets decreased with the increase of the amount of lipid.The gel thickness decreased and the strength increased with the addition of lipids,so the increase of gel strength was the main reason for slowing down the drug diffusion process.Compared with Kolliwax HCO,the compressibility and formability of the powder are better when adding Compritol 888.After tabletting,the porosity is lower.When Compritol 888 is added in drug layer,the release rate is slightly lower.When adding HCO to barrier layer,the water absorption,swelling and erosion rate of the tablets are higher.And the gel thickness and strength increase,so the release rate is lower than adding Compritol 888.Compared with mannitol,when the filler is lactose,the compressibility of the powder is better.But the porosity is higher.The types of fillers have no effect on the release rate.And the types of fillers in barrier layer have no effect on the water absorption,swelling and erosion rate.When using mannitol,the gel strength decreased but the thickness increased,so the drug diffusion path is prolonged,the release curve is consistent with the tablet using lactose.So the diffusion velocity is the main reason which affected drug release curve.The mainly mechanism of drug release is diffusion mechanism.In the study,we choose HPMCK4M as the hydrophilic matrix,the drug layer is 100mg and contains 40%HPMCK4M and 10%lipid,the barrier layers is 120+180mg and contains 60%HPMCK4M and 25%lipid.The combination of lipids and fillers are 888Man+888Man or HCOLac+888Man.The geometric sustained release tablets were pressed by the machine dies with a 11 mm round-shaped piece.The result of stability test show that moisture absorption of tablets increase when the amounts of HPMCK4M increase,the addition of lipids can reduce the moisture absorption.Temperature also has an important effect on the stability of the formulations.The release curves decrease slightly when there are lipids in barrier layers.