Preparation Of DET-LDH-ASP Hydrogel Matrix Sustained-released Tablets And Its Pharmacokinetics

1. Effects of Dextran and HPMC on Sustainable-release Properties of the LDH-Acetosalicylic Acid SystemAcetylsalicylic acid (ASP) was used as the intercalated guest of layered doublehydroxide (LDH) to prepare a drug-loading system LDH-ASP, as a sustainable release patternmodified by dextran (DET) and prepared with excipient hydroxy-propyl-methylcellulose(HPMC). Release properties of the HPMC-DET-LDH-ASP sustainable release tablet wasevaluated in this paper, to study the effects of dressing agent DET and excipient HPMC on therelease properties of LDH-ASP system and investigate the utility of LDH as a drug carrier inmatrix tablets. The sustained-release tablets were made by the direct powder compressionmethod using DET-LDH-ASP super-molecule as the main body and HPMCK15M as matrixmaterial; drug dissolution in different media was measured by ultraviolet spectro-photometricmethod. In the same medium, sustained-release effect of HPMC-DET-LDH-ASP tablet wasbetter than that of HPMC-LDH-ASP tablet, but the sustained-release effect ofHPMC-LDH-ASP was superior to that of ASP original drug matrix tablet. TheHPMC-DET-LDH-ASP sustainable release tablets showed different release effects anddifferent mechanisms in different media, in hydrochloric acid medium with a pH of1.0drugsspread outward from the non-dissolution gel hydrated layer formed in matrix, the sustainablerelease time was more than12hours; however, in distilled water or phosphate medium withpH6.8, drugs released through the dissolution mechanism and the sustainable release timewas less than6hours. In acidic medium, the sustainable release properties of the LDH-ASP transshipment system could be improved significantly through modifying with DET andperforming with HPMC.2. Study on the preparation of sustained-release hydrophilic matrix tablets of DET-LDH-ASPSustained-release tablets were made by the direct powder compression method usingDET-LDH-ASP super-molecule as the main body and HPMC as matrix material; and used f2factor for evaluation by orthogonal design optimization to filter gel matrix tablets of theprescription; drug dissolution in different media was measured by ultravioletspectro-photometric method. When the results of the HPMC, with viscosity of100Pa·s andcontaining sodium alginate for the amount of10%, reached the amount of40%, the preparedsustained-release tablets had obvious sustained-release effect, and the drug release patternfollowed the first order kinetics [ln(100-Q)=-0.163t+4.522,R2=0.9944]. The sustained-releasetablets reach the expectable results with reasonable formulation and simple technology.3. Study on the pharmacokinetics of the DET-LDH-ASP sustained-released tablets in rabbitsA single oral dose of50mg DET-LDH-ASP sustained-release tablets and50mg referenceaspirin sustained-release tablets was given to6rabbits, respectively. Drug concentration inplasma was determined by HPLC method. The pharmacokinetics parameters were fitted andcalculated by DAS2.0program. Study on the pharmacokinetics and relative bioavailability ofDET-LDH-ASP sustained-release tablets in health rabbits. The plasma concentration-timecurves of reference aspirin sustained-release tablets appeared to fit one compartment openmodel after a single oral dose, its main pharmacokinetics parameters was as follows: t1/2α=1.153h, cL=0.336h, AUC=138.536mg·L-1·h, Cmax=26.137mg·L-1, Tmax=3.56h; but theplasma concentration-time curves of DET-LDH-ASP sustained-release tablets appeared to fittwo compartment open model after a single oral dose, its main pharmacokinetics parameterswas as follows: t1/2α=2.4h, cL=0.186h, AUC=260.401mg·L-1·h, Cmax=27.60mg·L-1，Tmax=4.09h, and its relative bioavailability was129.598%. The DET-LDH-ASP sustained-release tablets show a good sustained-released performance and are bioequivalentwith the reference aspirin sustained-release tablets.