Study On Alginate Floating Sustained Release Microspheres

Floating drug delivery system (FDDS) is one of the special dosage form which can keep floating on the gastric fluid and sustain release the drug for a long time. It can raise absorption of drug and lower its adverse effect by prolonging its gastricretention time (GRT). In the present study, Vitamin B₂ and Diltiazem hydrochlorid (DTZ) were selected as the hydrophobic and hydrophilic model drug respectively. The object of the present experiment was to enhance bioavailability of both hydrophobic and hydrophilic drug by preparing floating sustained release microspheres separately by using alginate as material.Vitamin B₂ Ca-Alginate floating sustained release microspheres were prepared by using the needle dropping method and selecting alginate and NaHCO₃ as matrix and gas-forming agent respectively. Single-factor test methods were used to study the effects of the amount and types of excipients, prepared methods on the different performances of microspheres and screen the optimum formulation. The microspheres with optimum formulation showed ideal buoyancy and drug release characteristics. Drug releasing process of testing microspheres in SGF was accorded to Higuchi equation.Ca-Alginate floating sustained release microspheres were prepared by selecting DTZ as hydrophilic model drug. Compared with hydrophobic drug Vitamin B₂, DTZ Ca-Alginate microspheres showed lower drug loading and encapsulation efficiencies, and released the drug more rapidly. By the addition of chitosan, the drug loading and encapsulation efficiencies were notably enhanced while drug release can't be controlled effectively. So we attempt to coat the microspheres to make it sustain release and keep floating for 24h. The microspheres need to have good sphericity, high drug loading and encapsulation rate, excellent floating performances before being coated. Therefore, the prescription was determined by using orthogonal design test methods and selected three performances above as screening index.Eudragit RS 30D was selected as coating material and a fluid-bed spray processor was adopted for coating the DTZ alginate-chitosan floating microspheres prepared by the method of needle dropping method. The process variables were determined by using single-factor test methods. Results of the experiment showed that the coating microspheres can still float on simulated gastric fluid for 24 h with ideal drug release characteristics.γ- Scintigraphy was used for the study of stomach retention of ^99mTcO₄^- labled DTZ floating sustained release microspheres. As the results have shown, prolonged gastricretention time (GRT) of over 5h was achieved for the optimized coating floating microspheres and thus the floating performance of the formulation was confirmed.