Preparation And Study Of Pentoxifylline Osmotic Pump Tablets

Objective: Pentoxifylline is a vasodilator developed in the sixties.Owing to its wide use ,pentoxifylline is a hot subject in clinical research all along.But it is absorbed irregularly and eliminated rapidly,which makes it unconvenient in clinical use and brings unstable clinical effect with it.We attempted to use osmotic pump technique to increase its curative effet, educe its adverse effect and decrease the frequency of administration.Methods: Taking A,B,C,and D as four influencial factors,choosing three different levels respectively,we use L₉ (3⁴ ) orthogonal design to select the optimum formulation of tablet core.The dissolution rates of 5min and 10min were used as parameters.On the basis of pilot experiment and literature,we decide the composition and volume of coating solution.Cylindrical basket method was employed in the experiment of dissolution test. Pentoxifylline can be determined by using Ultraviolet spectrophotometer at a wave-lenghth of 274nm.The related substancrs in pentoxifylline can be separated and determined by High-performance Liquid Chromatograph (HPLC) with Ultraviolet detector.The liquid chromatographis eqqipped with a 274nm detector and a DIKMA C18 column. Mobile phase is a suitable filtered mixture of methyl alcohol-water-HAc(45:55:5).The flow rate is about 1.0ml per minute.The stability of the pentoxifylline osmotic pump tablets was investigated for a long-term testing.The pentoxifylline osmotic pump tablets(200mg) and enteric-coated tablets (200mg) were given in a single dose to five rabbits ..respectively.The pentoxifylline concentrations in plasma were determined by HPLC with Ultraviolet detector.The parameters were fitted and calculated by 3P87 program. The liquid chromatograph is eqqipped with a 273nm detector and a DIKMA? C18 column.Mobile phase is a suitable filtered mixture of acetonitrile -0.1MKH2PO4 (75:25). The flow rate is about 1.0ml per minute.We used internal standard method,and phenacetin is the internal standard.Results: The results of orthogonal experiment design were found.The optimum formulation of core tablet is A3B1C]D2 .On the basis of monofactorial investigation^ was determined that the proportion of X and Y is m.The release profiles of pentoxifylline osmotic pump tablets and pentoxifylline sustained release tablets in vitro could be described by zero-order kinetics and Higuchi equation: F(t) =1.3975+8.7483t(t^8h,r=0.9996),F(t)=18.3423+7.0635t(t^ 8h,r=0.9884);Q=0.3520tI/2-0.3044(r=0.9953),Q=0.2908t1/2-0. 087(r=0.9985).Isolation of related substances under theadopted chromatographic condition,the related compounds and pentoxifylline could be completely separated,and the content of impurity in pentoxifylline accords with demands.The in-vivo release of pentoxifylline complied with the first order kinetics,noe-compartment model.The parameters were: given pentoxifylline osmotic pump tablets: A=297.276 + 40. 5388 ; Ke= 0.1093 ± 0. 012045/h ; Ka= 0.7018 + 0. 2054/h; t,/2(Ka)= 1.4404 + 0. 2446h; t,/2(Ke)= 6.3975 + 0. 6728h; AUC = 2264..74 + 210. 88 (ng/ml)*h; CL/F(s)=0.0889 + 0. 008249mg/h/(ng/ml); T(peak)= 3.2257 + 0. 4787h;C(max)= 172.65 + 9. 2455 ng/ml; V/F(c)=0.8166 + 0. 0710 (mg)/(ng/ml) o The control: A=2726.97 ; Ke=0.3959/h; Ka=0.6102/h; Lag time=l.3364 h; t,/2(Ka)= 1.14 h; t)/2(Ke)= 1.75h; AUC =2418.22 (ng/ml)*h; CL/F(s)= 0.0827 mg/h/(ng/ml); T(peak)= 3.36h; C(max)= 430.51 ng/ml; V/F(c)= 0.2089 (mg)/(ng/ml).The result of t-test showed that there was significant difference between two groups parameters of Ke, t1/2(Ke), C(max), V/F(c) (P<0.01) and Ka, t,/2(Ka) (P<0.05) ,and no significant difference between two groups parameters of CL/F(s), T(peak),AUC.Comparing with enteric-coated tablets, the pentoxifylline osmotic pump tablets was characrerized by a good absorption, a slow elimination and a low C(max),that has the benefit of the elongation of releasing of the drug and the reduction of side effect.Conclusion: The in-vitro release of pentoxifylline...