Studies On Solid Dispersion Of Indomethacin And Its Enteric-coated Tablets

With the effects of anti-inflammatory, antipyretic and analgesic, indomethacin can reduce the prostaglandin synthesis, block the nerve impulses of pain in inflammatory tissue and suppress the inflammatory response through inhibiting the cyclooxygenase. Indometha- cin has been used in clinical for more than 40 years since it was marketed in 1963. Howev- er, it is water-insoluble, which results a low oral bioavail- ability and then greatly limits its clinical application. In this study the indomethacin was made into solid dispersion to improve the water solubility and dissolution rate. And then take the solid dispersion into enteric-coated tablets to enhance the drug dissolution and bioavailability. This is significant for reducing the dosage, weakening the side effects, imp- roving the efficacy and laying a foundation for clinical application. Detailed contents of this paper are as follows:1. The establishment of analysis methods in vitroThis paper established a method of UV to determine the in vitro release of indomethacin solid dispersion. The results indicated that the pharmaceutic adjuvant had no effects on the absorption of indomethacin. The average recovery rate of indomethacin was close to 100%; And indomethacin is stable in the artificial intestinal juice under PH6.8 within 24 hours.Establish a high performance liquid chromatography to assay the containment of indomethacin solid dispersion of coated tablets. The results demonstrated that the method was fast, sensitive and specific, which could meet the requirements of methodology.2. Preparation of indomethacin solid dispersion and its StabilityThe solid dispersion prepared in this research can significantly increase the dissolution of indomethacin. The X-ray diffraction shown the indomethacin existed in the solid disper- sion as the way of amorphous or micro-lens dispersion status. The Fourier infrared scan spectra confirmed there was no interaction between the carrier and indomethacin during the formation of solid dispersion. The scanning electron microscopy validated the solid dispe -rsion was different from the active pharmaceutical ingredient and and physical mixtures. The in vitro release experiments displayed that the release behavior would change under different dissolution method and speed.The impact of factors and long-term experiments illustrated that the appearance, disso- lution and content of indomethacin solid dispersion could maintain the same as before under high temperature, humidity and light condition. But in high humidity conditions, the indomethacin solid dispersion would tend to absorb moisture so as to become heavier. The dissolution reduced at 15min with a decrease in content. The physical properties, content and dissolution of indomethacin solid dispersion shown no change after keeing at room temperature for three months.3. The preparation of indomethacin solid dispersion tabletsPrepare the indomethacin solid dispersion tablets by direct compression method. First take the disintegration time to film and the flow of materials as as the main index of examination to make a single factor research. Thus screen proper disintegrating agents, fillers, lubricant types and their usage. And then optimize appropriate films, disintegrating agents and compressing pressure by three factors and three levels orthogonal experimental methods. The obtained final prescription of indomethacin solid dispersion tablets was as follows: 100mg indomethacin solid dispersion, 272mg micro-direct pressure crystalline cellulose and lactose (1:1), 24mg PVPP, 4mg magnesium stearate(400mg / piece). The dissolution of solid dispersion was apparently higher than ordinary tablets. The critical relative humidity of sheeting material was 68.57%, indicating that relative humidity should be controlled at 68.57% or less.4. Study on indomethacin solid dispersion of film coating technologyThis study used enteric-coated materials Eudragit L100-55 to prepare indometacin solid dispersion enteric-coated tablets by thin-film coating technology with simple process and good reproducibility. The enteric-coated tablets had no lobes and collapse in HCL solution (0.1mol / L) for 2h, and the release rate could accord with Chinese Pharmacopoeia requirements in the phosphate buffer (pH6.8). The liquid coating formulation is as follows: 15g Eudragit L100-55, 1.5g PEG6000, 4.5g talcum powder, 230g ethanol. Optimum coating conditions are below: the tablets are set in the coating pan at the angle of 40°with the speed of 20r/min and 40 ~ 50℃hot air to warm tablets. Then adjust the gun to inject at 1. 5mL/min. After film coating, take the coated tablets into the oven to heat for 2 hours.