Preparation And Evaluation On Amorphous Solid Dispersions Of Indomethacin

Non-steroidal anti-inflammatory drug indomethacin has the effect of antipyretic, analgesic, anti-inflammatory, and is used for ankylosing spondylitis, rheumatoid arthritis, osteoarthritis patients who are intolerant to aspirin or the curing aren’t satisfactory with the drug aspirin. Indomethacin belongs to BCSII drugs, which are of high permeability and low dissolution,but these drugs are the largest candidates that were researched and developed in pharmaceutical area. After preparing amorphous indomethacin solid dispersion, the in vitro release property and the in vivo bioavailability evaluation were carried out, and the results met the requirement.Taking new carrier materials Soluplus and Co-PVP as the research object, this paper examined the particular characters and their crystal suppression effects. The cloud point determination results showed that Soluplus cloud point was dependent on the solution pH, which decreased with the pH increased. The Soluplus solution may be more likely to form micelles, to improve the poorly soluble drugs dissolution. The critical micelle concentration results showed that Soluplus had lower CMC, which is helpful to improve the dissolution of indomethacin solid dispersion. At temperature of25℃and37℃, supersaturated solution crystallization inhibition test results showed that the temperature had an influence on the Soluplus and Co-PVP crystal suppression effect, and at these two temperatures Soluplus had a stronger crystalization suppression effect on indomethacin to Co-PVP. Soluplus had the surfactant character, which played an important role on crystalling suppression. In addition, Soluplus contained a lot of hydrophilic groups which could formed more hydrogen bonds with the drug to inhibit drug crystallization rate, and this was the important factor on the strong crystallization inhibitory effect.Referring to the foreign and domestic documents on solid dispersion, this paper prepared1:1,1:3indomethacin solid dispersion by solvent evaporation methods, and the contents were determined, which showed that the indomethacin solid dispersion content was consistent with the theory values. By differential scanning calorimetry and powder X-ray diffraction techniques, whether the amorphous system was formed in indomethacin solid dispersion could be identified. Using Fourier transform infrared spectroscopy, whether or not a solid dispersion interactions was existed and the interaction strength between indomethacin and the ingredients could be speculated. PXRD and DSC results showed that the two materials of different proportion were of solid amorphous dispersion patterns. Co-PVP and Soluplus were amorphous patterns, and amorphous solid dispersion formed by the patterns had the advantage of high quantity drug loading. FT-IR results showed that hydrogen bonds were likely formed between indomethacin and the carriers of Soluplus and Co-PVP in amorphous solid dispersion, which improved the stability of the amorphous solid dispersion.The in vitro dissolution of the prepared samples was determined, and the results showed that the amorphous solid dispersion patterns of Soluplus-indomethacin and Co-PVP-indomethacin significantly improved the dissolution rate. In the pH7.4PBS medium, indomethacin in the two carriers solid dispersion could dissolved completely, and the1:1Co-PVP solid dispersion dissolution rate was faster than the1:1Soluplus solid dispersion. The dissolution profiles of the solid dispersion were identical in media of pH6.8PBS, pH6.5PBS, pH6.0. While, the1:1Co-PVP dissolution rate was higher than1:1Soluplus dissolution in media of Medium of pH4.5, pH5.0, pH5.5PBS. In brief, Co-PVP and Soluplus could significantly improve indomethacin dissolution and the former was more excellent.Of high indomethacin content,1:1solid dispersion samples were chosen to carry out the pharmacokinetic evaluation. The PK evaluation results showed that Co-PVP solid dispersion decreased the time to achieve the maximum concentration, increased the Cm, and had the higher relative bioavailability.