Study On Piperazine Ferulate Sustained-Release Tablets

Piperazine ferulate (PF) is a non-peptide endothelin receptor antagonist, and a derivate of ferulic acid that reside in Chinese Angelica and Szechwan Lovage Rhizome. The agent is used in clinic for the treatment of Cardiovascular and renal glomerulus dieases with hematuria and blood coagulation. In this article, PF 12 h hydroxypropylmethyl cellulose matrix sustained-release tablets was prepared in order to reduce the frequency of administration and fluctuations of blood concentration.A ultraviolet spectrophotometry method was established to determine the content and drug release in vitro of PF sustained-release tablets.Direct compression was introduced to prepare the preparation of PF sustained-release tablets that contained 150 mg PF per tablet. Take accumulated release as an index, we performed experiments focused on drug release affected by the use of different types of HPMC as matrix single or combined, as well as the use of octadecanol, EC, carbopolc, sodium alginate, chitosan, CMC-Na as regulator. Besides, other fators affected the drug release such as formulation, preparation and measurement of drug release were also evaluated. On the basis of mono-factor investigate, synthetic graded value as the parameter, a central composite design-response surface methodology (CCD-RSM) was carried on to optimize the two most effective factors-content of HPMC and CMC-Na. The optimized formulation of the PF sustained-release tablets was (weight percentage of the whole pill):PF 50.0%, HPMC 20.5%, CMC-Na 18.6%, Talc 3.3% and Lactose 7.6%, according to both mathematical model and graphics.Primary research of stability indicated that PF sustained-release tablets were stable at high temperature, but sensitive to high humidity and light, which suggested a sealed and dry preservation.The mechanism was discussed to explain the kinetics and principle of drug release from gel matrix. A synergism of Fick diffusion and erosion was concluded. And due to the use of CMC-Na, the erosion of the matrix was strengthened, and the drug release from the matrix completely.Finally, the plasma concentration in six Beagle dogs was determined by HPLC after a single oral administration of commercial immediate release formulation and self-made test formulation. The pharmacokinetics parameters of test and reference formulation were A UC0→t 6.61±1.25μg·h·ml-1 and 6.69±1.31μg·h·ml-1, cmax3.72±1.29μg·ml-1 and 8.81±2.29μg·ml-1, tmax 1.29±0.19 h和0.47±0.17 h, MRT 2.85±0.38 h and 0.57±0.18 h respectively. The relative bioavailability of PF sustained-release tablets was 99.5±11.6%. A prominent decreased cmax and prolonged MRT illustrated "sustained-release" characters in self-made preparation.