The Stachydrine Sustained-release Tablets And Quality Evaluation

Stachydrine is the primary effective constituent of Leonurus heterophyllus Sweet. Base on the studies of the influence of formulation and manufacture on the release of Stachydrine, the sustained release tablets (SRT)of twice daily administration were prepared with HPMC K100M and other accessories.First, quality control method of stachydrine was studied. In this study,the structure of stachydrine was conformed by LJV, IR, MS, NMR along with its physical-chemical property concluded with absorption coefficient, specific rotatory power, ect.Since quality standard of stachydrine and its preparations have not been recorded into internal or overseas pharmacopeia yet, quality control method of stachydrine was studied exploringly in the paper. Establish themethod of identification of stachydrine with IR and TLC. Study the hygroscopicity of different crystal structures in H₂O, C₃H₆O and C2H6O. Check of foreign matter was made and the impurity had been set limit to.The factors influencing of alkali, oxidation and light included stachydrine(crude) were tested with TLC, drug-related impurities were analyzed, then sample oneself control method was used for delectability determination, the limit of drug-related impurities was 1% for raw drugs.RP-HPLC was developed for the assay of content and dung-related impurities in raw drugs and SRT. AQ C18 column (150mm×4.6mm, 5μm) with UV detection at 203 nm, and the mobile phase consisted of p hosphoric solution(0.1mol/L) and adjusted to pH5.5 with phosphoric acidwere used to study on quality standard and formula optimization for SRT. The calibration curve was linear (r-0.9999) within the range of 2～20μg/ml, Reinject (RSD=0.32%); within-day precision (RSD=0.43%), reproducibility (RSD=0.11%); average recovery rate of SRT is 99.9%, RSD=1.01%. Result of drug-related impurities＜1%, impurities macula was sightless.We developed a determinant standard by the way of releasing rate in0～8hr. HPMC K100M was choiced to be the matrix material; the micro-spherical silica gel improved the moisture absorption of drugs and decentrality; accession of retarder proved the retardarce on drug release, it extended the drug releasing obviously, isinglass was choiced finally. Base on the studies of the influence of formulation and manufacture on the release of stachydrine, the sustained release tablets were prepared with HPMC K100M and isinglass. The formulation were optimized by orthogonaldesign, having the accumulative release amount of 1hr, 4hr and 8hr asthe evaluation target. The study showed that the drug release characteristics, appearance and the content of the well packaged preparation did notchange after stored under 40℃and RH65% environment for three monthS.The release of stachydrine could be described as Fickian diffusion, which was mainly by diffusion from gel layer associated with tablet pervasion, and erosion act no contributions to the drug releasing.