Preparation Of Ambroxol Hydrochloride Osmotic Pump Controlled Release Tablet

Ambroxol Hydrochloride was the metabolites of Bromhexine, it is used to cure many kinds of urgent and slow breath diseases going with the symptom of phlegm and ovcrabun -dance grume secretion, Nowadays, there are tablets,oral liquids,soft capsule on the market ,the half-life of the common pharmaceutical is two to three hours, so the medicine must be used frequently ,it is no convenient in the clinical application. Manufacturing Ambroxol Hydrochloride modified-release tablets which is used one time everyday, it can reduce the side-effects to the intestinal and stomach, it also can decrease the times of having medicine and the difference of patient on the greatest degree. So it is very convenient to patient, at the same time it can relong the effectiveness of the tablets.In this paper , Taking lactose, citric acid, PEG6000, and adhesive as four influencing factors based on the preview experiments, choosing three different levels respectively. we use L₉ (3⁴) orthogonal design to select the optimum formulation of tablet core. Using the interrelating math of the returning line and the accumulative dissolution percents of 2h, 6h and 12h as parameters to sift the formulation of tablet core ,at last we can get the best formulation: lactose 180mg,citric acid 120 mg,PEG6000 60mg,the adhesive is 8% PVP solution. Preparing coating tablet on different conditions ,inspecting the factors which can affect medicine release, the final form of the coating liquids is definited, the proportion of surelease to PEG400 is one to one, the increasing weight of coating is 3.0%.Oar method was employed in the experiment of releasing degree test. The release profiles of Ambroxol Hydrochloride osmotic pump tablets and Ambroxol Hydrochloride sustained release capsule in vitro could be described by zero-order kinetics and Higuchi equation: F(t)=4.1051+7.9936t (t≤12h, r=0.9880) ; F(t) = 21.434 + 6.2228t (t≤12h, r=0.9782) ,F(t)=36.879t^1/2-33.826 (r=0.9865)å’ŒF(t)=28.997t^1/2-8.7941 (r=0.9963) ,one can see the release curve of the preparation accords with the zero-order model better ,while the sustained release capsule on the market accords with the Higuchi equation better ,so the result shows the modified release effect of the osmotic tablets is good.The related substances experiment indicates determining the impurities in Ambroxol Hydrochloride by inverse High-performance Liquid Chromatograph (HPLC) possessing the traits of separating well and being quick,accurate. The separating degree of the sample mean peak and other impurities is fairly good, the content of the related substances is lower than 1.0%, so it accords with the demands. Determining the content of three batches Ambroxol Hydrochloride osmotic pump tablets by High-performance Liquid Chromatograph, they are 99.78%, 99.62%,99.18%.Lay the self-making Ambroxol Hydrochlorideosmotic pump tablets in the sealed accelerating test condition(40℃±2℃,RH75%±5%), determining the proportion of the solution respective -ly after one month,two months,three months and six months.Compound three kinds of sodium chloride solution (the value of the osmotic press is according to literature reporting) the density is lmol/L,2mol/L,4mol/L,the solution is used as releasing medium to inspect the releasing mechanism of the preparation. The releasing degree of the Ambroxol Hydrochloride osmotic pump tablets reduces with the adding medium osmotic press, it shows the osmotic press is the main mechanism of the release.Carry through bioavailability experiment with Ambroxol Hydrochloride modified release tablets and sustained release capsule in the body of the rabbit, the result indicates both are according with the model of first-order knetics, bioavailability of the Ambroxol Hydrochloride osmotic modified release tablets corresponds with the sustained release capsule, it absorbs well and eliminates slowly, which is benefit to the lasting exertion of the effect and the reducing of side effect.