Study On Sustained-Release Capsule Of Doxazosin Mesylate

Doxazosin Mesylate(DOX)is a selectedα1- Adrenoceptor antagonist,which can dilate blood vessels,reduce vascular resistance and lower blood pressure by selectively blockingαadrenergic receptor in prostatic smooth muscle matrix,biofilm and bladder neck.DOX is mainly absorpted in the gastrointestinal tract,so it is mainly oral dosage form in the market.However,the dose is difficult to control in the ordinary drug delivery systems and there are many adverse reactions(ADR)such as orthostatic hypotension.Therefore,we develop a new dosage form the DOX-loaded sustainedrelease pellet capsules.Through comparing the quality of appearance,resting angle,particle size distribution,fragility and yield,we investigated three different crafts in preparation of the drug-loaded pellets,and ultimately,we selected coating blank pill as the optimal craft.75%ethanol solution containing 1%HPMC(5cps)was selected by single factor in the solvent type and dosage perspectives.By investigating DOX-loaded sustained-release pellets coating formulation and coating technology,the optimal coating formulation was determined as follows: EudragitRL 100∶EudragitRS 100(8∶2)as sustained-release material,coating liquidsolid content(8%),10%TEC as plasticizer,15%talc inside,0.1%talc outside and appropriate 95%ethanol.Meanwhile,we adopted spray coating suspending technology at the bottom of a fluidized-bed and investigated the influencing factors such as the intake air volume,coating temperature,peristaltic pump infusion rate and nozzle atomizing pressure.Ultimately,the optical coating craft was selected as follows:100g stuff,20%coating weight,air flow regulated through the blower in fluidized bed of 37 Hz,0.1 MPa spray pressure,permanent peristaltic pump flow rate of 1.0 rpm,coating temperature of 25-30℃.The HPLC method was used to determine DOX in the sustained-release pellets capsule,and this method was proved to be accurate and reliable.After the determination of the detection wavelength,the linearity test and the recovery test,the ultraviolet spectrophotometry method was established for determining the DOX release in vitro from sustained-release pellet capsules.The DOX release in vitro from sustained- release capsules was compared with that of the reference preparation (Cardura XL)by introducing similar factor f₂ as evaluation index.The results(f₂= 73.73＞50)showed a high similarity between the release behavior of the reference preparation and that of the test preparation.The HPLC method was established for the detection of the relative substances of DOX sustained-release capsule,which laid the ground for the study of the drug stability.The stability of sustained-release pellet capsule under the conditions of light (4500 LX),high temperature(60℃),high humidity(RH 92.5%),six months of accelerated test and long-term placing experiment was detected.The results showed that the indicators were all in accordance with the regulations.In conclusion,the DOX-loaded sustained-release pellet capsule was very stable.