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The Development of TPsustained-release Tablet and in Vivo-in Vitro Correlation

Author: YangJunYi
Tutor: JiangXueHua
School: Sichuan University
Course: Pharmacy
Keywords: Sustained-release tablet Optical activity Pharmacokinetics In vivo-in vitro correlation
CLC: R943
Type: Master's thesis
Year: 2003
Downloads: 353
Quote: 1
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Abstract

The paper discussed the thinking and the pathway of the manufacture of sustained-release form based on a optical activity-TP as model drug by using the principles of biophamaceutics and pharmacokinetics. The thesis adopted HPMC as the basic matrix material, pregelatinized starch as compression aids, magnesium stearate as lubricant.The TP sustained-release tablet was prepared which could release twelve hours continuously in vitro.The basic prescription and preparation technology was initially defined by the study about formulation screening and technology optimizing ,based on the pharmacy rule as indicator and the stability maintaining of optical activity as premiss.Dissolution rate is an important factor of influencing internal quality of tablet. The determination method was initially set up for the dissolution rate of the TP sustained-release tablet. And the various factors were studied,which influence the TP release of TP sustained-release tablet.Orthogonal project was employed to screen the prescriptions which based on the study of mono-factor experiment. Verification experiments about the dissolution rate of optimized prescription were done . The results showed that the dissolution rate of TP among the TP sustained-release tablets at 2h,6h,10h was 15~35%,40~60%,>75% respectively.The f2 similar factor analysis explained that the recur capability of TP sustained-releasetablets releasing was good and the craft was stable.The quality study of the TP sustained-release tablet was done.The main components included that the identification methods were set up,the HPLC method was established for the content determination of the TP in the TP sustained-release tablet by the comparison of UV method and HPLC method, and the TP sustained-release tablet examining method of the correlated material was founded. The studing results according to items of the quality evaluating showed that evaluating method was reasonable and the quality of the TP sustained-release tablet was under the control. The release law of the TP sustained-release tablet was studied, the Ritger-Peppas equation describes the law,and the n,the releasing parameter,equaling to 0.7439(0.45<n<0.89) meaned that the release mechanism was a synergism of diffusion and matrix erosion.The initial stability study showed that high temperature and light have not obvious effects on the TP sustained-release tablet but the humidity was of influence. The result gave a clue that the TP sustained-release tablet should be packed in moistureproof material and preserved under dry enviroment.The pharmacokinetics and bioavailability study of the TP sustained-release tablet in dogs was made.The HPLC method which determinates the TP concentration in the dog plasma was established.The results of the method evaluaion and pharmacokinetics experiment showed that the method could satisfy the needs of experiment and study. As the TP ordinary tablet being the reference preparation,experiments of single and multiple dosage regimens were done by self-comparison crossing trial design.The result indicated that the TP fits the one-compartment. After administering single dosage of the sample and the reference preparation to dogs respectively, AUC0-t is 1463.1 223.9 ng-h-ml-1 and 1443.3 262.2 ng h ml-1 respectively; tmax is 4.5 0.3 h and 1.5 0.3 h respectively, Cmaxis 151.3 20.5 ng-rnl-1 and 338.5 69.3 ng-ml-1 respectively. Afteradministering multiple dosage to dogs, AUC0- is 1557.2 92.3 ng h ml-1 and 1554.2 81.8 ng h ml-1 respectively; tmax is 4.4 0.2 h and 1.7 0.3h respectively; Cmax is 208.9 6.7 ng ml-1 and 430.5 26.0 ng ml-1 respectively;Cav is 129.8 7.7 and 259.0 13.6 respectively;DF is 121.1% 16.3% and 144.4% 13.5% respectively;Cssmin is 51.7 15.01 ng-ml-1 and 56.5 18.3 ng ml-1 respectively; relative bioavailability of single and multiple dosage regimens is 102.0 % 6.2 % and 100.2 % 5.4 % respectively.The evaluation result of bioequivalence showed that AUC is bioequivalent but Cmax and tmax are beyond the confine . The Cmax and the DF

The Development of TPsustained-release Tablet and in Vivo-in Vitro Correlation

Abstract

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