Preparation, Evaluation Of Tanshinones Ternary Solid Dispersions And Research On Its Fast-Disintegrating Oral Tablets

OBJECTIVE:(1) To prepare Tanshinones ternary solid dispersions and study its in vitro dissolution characteristics.(2) To develop a reversed phase high performance liquid chromatographic method (RP-HPLC) for determining the concentration of Tanshinoneâ…¡A in rat plasma,and this method was developed for application in the pharmacokinetics study.(3) To prepare and evaluate Tanshinones ternary solid dispersions fast buccal disintegrating tablets.METHODS:(1) The Tanshinones ternary solid dispersions,consisting of Polyethylene Glycol 6000(PEG6000),Sodium Lauryl Sulfate(SLS),were prepared by the solvent-melting technique,and research on its solubility and dissolution.Differential Scanning Calorimetry(DSC) and Fourier Transform Near Infrared Spectroscopy (FT-NIR) were used to characterize these systems.(2) The assay was conducted on a VP-ODS C₁₈ column(4.6 mm×150 mm;5μm), and the mobile phase was consisted of methanol and 0.02 mol/L ammonium acetate buffers in a volume ratio of 78:22.The flow rate was 1.0 mL/min.The detection wavelength was set at 270nm.Testosterone propionate was used for internal standard. The plasma concentrations of Tanshinoneâ…¡A were determined after oral administration of Tanshinones Ternary Solid Dispersions.And pharmacokinetics parameters were estimated by DAS1.0.(3) Microcrystalline cellulose,low substituted hydroxypropylcellulose were used as disintegrants and magnesium stearate were used as lubrieatal materia,fast disintegrating tablets could be prepared by direct powder compression method.The properties of these tablets were investigated according to the instruction of the Chinese Pharmacopoeia (2005).RESULTS:(1) The results showed that the solubility and dissolution rates of TANâ…¡A were substantially increased in the SDs systems than in physical mixtures(Phy mix). The DSC and FT-NIR spectra analysis revealed that TANs SDs was in an amorphous or molecule state.(2) The bioavailability of TANs in ternary SDs was 1.88 times than that of in binary SDs.(3) The major ingredients in the optmized formulation of the tablets included 20 mg TANs,40%microcrystalline cellulose,9%low-substituted hydroxypropylcellulose,1% magnesium stearate.The disintegration time was 22.6 s,tested appearance,hardness, weight-difference,brokenness and dissolution met the request of the Chinese Pharmacopoeia(2005) standard.CONCLUSION:(1) This study demonstrated that ternary SDs is an effective strategy in improving the dissolution and bioavailability of poorly water-soluble drug.(2) The method developed was simple and reliable and could be used to simultaneously determine the TANâ…¡A in rat plasma.(3) The prepared orally disintegrating tablets are quick to disintegrate,release and have desirable taste.NEW IDEAS:(1) The preparation,characterization and evaluation of Tanshinones Ternary Solid Dispersions were proceeded for the first time.(2) The preparation and evaluation of Tanshinones Ternary Solid Dispersions fast disintegrating tablets were proceeded for the first time.