The Penetration Of Doxofylline The Pump Controlled Release Tablets And Study Of The Matrix Tablets

In this paper doxophylline was selected as the model drug to prepare the osmotic pump tablet and matrix tablet. On the basis of the pre-formulation research about the properties of doxophylline, excipients and cellulose acetate (CA) free film, polyethylene oxide (PEO),carboxymethylcellulose sodium (CMCNa), hydroxypropylmethylcellulose (HPMC), potassium chloride and sodium chloride were used to make the two-layer tablet core coated with the CA coating comprising with 10% polyethylene glycol 6000 (PEG6000).And HPMC was selected as the matrix material to prepare the sustained-release tablet. The system research of the doxophylline osmotic pump controlled-release tablet was made mainly. The effect of some factors on the drug release from the osmotic pump tablet was investigated. The result was the content of drug in the core tablet, the content variation of osmopolymers and the mass of the push-pull layer had significant influence on the drug release; but the sort of osmopolymers, the mass of the drug layer, the composition of the push-pull layer and the size of orifice for drug delivery had not. According to the experimental design of orthogonal test, coating thickness, the PEG sorts and content variation in the coating solution were selected as the causal factors. The linear correlation coefficient of the accumulative drug release amount and time (r) and the accumulative drug release amount (F%) were used as the evaluation standard to optimize the coating formulation. The zero-order release of the drug from the osmotic pump tablet could sustain to 12 or 24 hours with the thickness of coating varying. The result of the drug release mechanism study indicated that the drug release was mainly modulated by the osmotic pressure difference between inside and outside of the coating and the swelling force of the push-pull layer of the core tablet. The osmotic pump tablets were unstable under high temperature or humidity circumstance. The effect of some factors on the drug release from the HPMC sustained- release matrix tablet was investigated. The result was the viscosity and content variation of HPMC and the content variation of additive had significant influence on the drug release. The drug release from the matrix tablet could sustain to 12 or 24 hours with the content of HPMC varying. The matrix tablets were stable under high temperature or humidity circumstance. Using the immediate release tablet as the reference, the pharmacokinetics 3 of doxophylline sustained-release tablet and osmotic pump controlled-release tablet were studied, The result indicated that after p.o. 300mg doxophylline, AUC~.,. of the three formulations in turn were 5.67, 5.51, 6.01 (~ig/ml)h; Tm were 1.5, 4.0, 5.7 h; Cm were 2.57, 0.69, 0.48 ~tg/ml. The relative bioavailability of the sustained-release tablet was 97.2% and that of the osmotic pump controlled-release tablet was 105.9%. The drug release from the two kinds of tablets was equal in vitro and in vivo.