Study On Tetrandrine Calcium Alginate Sustained Release Gel Beads

Calcium alginate gel beads were widely used as drug carriers, which were obtained by the gelation of sodium alginate with divalent cation as Ca2+. Tetrandrine (TET), the calcium antagonists of Traditional Chinese Medicine, was selected as model drug to prepare calcium alginate gel beads. The coating process was performed on a fluid bed spray coater with Eudragit RS 30D and Eudragit RL 30D as the coating materials. The researches made were as follows:(1) Ultraviolet (UV) spectrophotometry method was developed for determination of physicochemical properties, content and drug release; High-performance liquid chromatography (HPLC) method with UV detection was applied to detect the stability of TET powder and solution as well as the plasma concentration of TET in dogs. Atomic emission spectrometry (AES) method was firstly adopted to study the release mechanism of calcium alginate. Analytical methods above were precise, simple and reliable.(2) Acid-dye colorimetric method was firstly applied to study the absorption of TET from intestine by utilizing intestinal absorption experiment of rats in situ. The results suggested that the intestinal absorption of TET was suitable for first-order kinetics via passive transport mechanism.(3) In the preformulation research the physicochemical properties of TET were investigated, which were connected closely with dosage form design. Equilibrium solubility(37 C)in distilled water, 0.1mol/L hydrochloric acid (HC1), pH6.8 phosphate buffer solution (PBS) and apparent oil-water partition coefficient in different pH value were determined relatively. Exposed to temperature, moisture and oxygen except light, the content of TET remained unchanged. And the stability of TET in water, 0.1mol/L HC1 and pH6.8 PBSwere good within 24 hours.(4) The preparation design was divided into two parts. The influences of formulation and manufacture on the entrapment efficiency, degree of circularity and drug release of gel beads were studied firstly, and orthogonal test was used to optimize the formulation. Then based on the studies of coating factors, the coating formulation was obtained by full design test. The way of TET released from gel beads could be described as non Fickian diffusion, which was mainly by matrix erosion.(5) To study the physicochemical parameters of sodium alginate, the content, intrinsic viscosity , average molecular weight and G/M value were determined, which were 96.13%, 0.1916Pas-1, 3.10+105 and 0.65, respectively.(6) The studies of pharmacokinetics in dogs indicated that the desired purpose of sustained release was achieved. Plasma concentration maintained relatively constant for more than 12 hours. Its relative bioavailability was 106.13%. The release of sustained released gel beads in vitro was correlative with absorption fraction in vivo well.