Studies On Octreotide Acetate Microspheres For Injection

In recent years, an increasing number of peptide and protein drugs have been playing play an important role in the diagnosis, treatment or prevention of disease as a vaccine. Octreotide was a synthetic octapeptide derivatives, which was therapeutical for the acromegaly and stomach intestinal pancreatic endocrine tumors. The maketed microspheres of octreotide acetate for injection use were prepared with glucose PLGA copolymer (GLU-PLGA). In this paper, the straight-chain PLGA was employed to prepare microspheres of octreotide acetate.In this study, the high-performance liquid chromatography (HPLC) method was established to measure the content of octreotide acetate and the release behavior of octreotide acetate microspheres in PBS (7.4). The results of drug stability studies under various conditions displayed that drug was stable under the condition of freezing and cold storage within 1 month and degraded a little under room temperature away from light, and was unstable in the illumination and should be preserved away from light, while it could be stable in PBS (pH 7.4) release mediums for seven days. Drug solubility experiments showed that the drug was easily soluble in water, slightly soluble in methanol and insoluble in most organic solvents.The multiple emulsion-solvent evaporation method (W/O/W) was adopted to prepare octreotide acetate microspheres. The optimal formulation was obtained through singal factor investigation and central composite design response surface design. The optimized formulation and technology:the drug feed 6.25%, PLGA (RG503H) 150 mg, homogenizing rate and time of primary emulsion 13500 L-min-1 and 60 s, stirring rate of second emulsion 2520 rpm, volume of CH2Cl21.80 mL, concentration of PVA 1.64%, concentration of NaCl 1.20%. And the octreotide acetate microspheres was prepared as the optimized formulation and technology.The microspheres obtained were round, regular, smooth, morphologically with the mean particle size of 51.4μm, drug loading of 5.5%, entrapment efficiency of 88%. The cumulative release of octretide from microspheres during 30 days was up to 80% which suggested the preparation illustrated a significant delayed release effect. The release behavior was in accordance with the zero-order release equation with a correlation coefficient of 0.9959. The accelerated test showed that the preparations could be stable within one month.In vivo ELISA method was set up to determine the content of octreotide in blood. The avalible prepartion and self-made micropheres were i.m. to Beagles, respectively and blood concentration was examined to evaluate the in vivo release of octreotide. Compared to the refenrence preparation, AUC o-tand MRT of octreotide was 87.98% and 92.97% of Sandostatin LAR(?) Depot. The relative bioavailability of microphere was 87.98%, which presented the obvious prolonged effect.