Preparation And Pharmacokinetic Study On Ranitidine Hydrochloride Loaded Hollow Sustained Microspheres

Hollow microspheres are a type of microspheres with hollow space inside. They have become one of the hot topic in pharmaceutical nowadays , because they possess the excellent floating capability as a result of the hollow space inside. They can prolong the gastric residence time of drug, maximizing the absorption and improving the bioavailability when used as drug carrier.The solvent diffusion and evaporation method was frequently used to prepare hollow microspheres in current researches. Methanol, dichloromethane or methylene chloride which relatively toxic was often used as solvent.In this study, hollow microspheres were prepared by a solvent diffusion and evaporation method. Choosing ethylcellulose (EC) as polymer and ethanol/ether as solvents which less toxic.Selecting ranitidine hydrochloride as a model drug to prepare RH hollow microspheres. The purpose is to prolong the gastric residence time, thus maximizing the absorption and improving the curative effect because of the excellent floating ability of the microspheres. The technique, drug loading, releasing and floating efficiency in vitro, physical and chemical character, stability, and the pharmacokinetics on rabbit are discussed in this article. The yield, mean diameter(MD),loading efficiency(LE) and shape of microspheres were used to evaluate the influence of different formulation and preparation factors. Use L9(34) orthogonal experiment to select the best recipe.The results showed that the best formulation was: ethanol: ether (v/v) = 6:1.0, RH: EC10 (m/m) = 4:6, T= 30℃, rotating speed 300 r/min. The yield of the prepared microspheres was 85.27%, the mean diameter was 579μm and the loading efficiency was 23.93%. The microscope photos and scanning electron microscope photos confirmed their hollow structure. The vitro release results showed that the common capsule release over in 1h, the common micropsheres reach balance in 10h, whereas the hollow microspheres sustained release until 24h in 0.1mol/L HCL. The common capsule and common microspheres nearly have no floating efficiency but the floating ratio of hollow microspheres can keep 75% after 24h. The stability test confirm the hollow microspheres are stable under high temperature(60℃), high humidity (25℃,RH90%±5%), light(4500LX±500LX), accelerated test(40℃±2℃,RH75%±5%).As compared with common capsule and common microsphere capsule, the Cmax of RH-hollow microsphere capsule had dropped from 6473.3ng/mL and 7164.4ng/mL to 4202.2ng/mL, Tmax had been prolonged from 0.48h and 0.21h to 2.76h, respectively.Relative bioavailability was 301.8% and 283.6% from rabbit pharmacokinetics studies. The blood concentration-time curve was sustained decline.