Research On Nimodipine Controlled Release Drug System Based On The Principle Of Osmotic Pressure

Nimodipine is a second-generation dihydropyridine calcium channel blocker.It is the main drug for clinical treatment of hypertension and ischemic cerebrovascular disease.It can increase cerebral blood flow without stealing blood and does not affect Features such as brain metabolism can significantly reduce ischemic brain injury.However,it has the problems of short biological half-life,strong liver first pass effect,low bioavailability,and low solubility in gastrointestinal juice.Commercial products need to be administered frequently,which limits the development of drugs.In order to improve these problems,this article combines nimodipine and osmotic pump technology to prepare nimodipine osmotic pump capsules based on the principle of osmotic pressure,optimize the preparation process and prescription of the capsule shell and contents,and stabilize the formulation the study.Established HPLC quantitative analysis method of nimodipine and UV in vitro release determination method.Through the appearance of the capsule shell,the results of electron microscopy and the cumulative release in vitro,it is determined that the dipping method is used as the capsule shell preparation process.Using similarity factor f2 as an indicator,single-factor investigation was conducted on the prescription and dosage of the contents of the capsule core of nimodipine osmotic pump capsule,and the composition of the capsule shell of the osmotic pump.The cumulative release of the drug in vitro and the degree of fit with the zero-order equation are used as evaluation indicators to determine the best capsule shell and content prescription for the nimodipine microporous osmotic pump capsule:the shell membraneforming material is cellulose acetate(CA),the penetration enhancer is polyethylene glycol 400(PEG 400),the plasticizer is triethyl citrate(TEC),the porogen is polyethylene glycol 6000(PEG 6000);the content is divided into two parts,one part contains Part of the medicine particle layer is the expansion boost layer.The drug-containing granular layer is made of nimodipine as the main drug,polyethylene oxide 200,000(PEO 200,000)as the suspending agent,sodium chloride(NaCl)as the osmotic active substance,and microcrystalline cellulose(MCC)as the diluent The particles are made;the booster layer is made of polyethylene oxide 8 million(PEO 8 million)as the expansion agent,NaCl as the osmotic active material,and hydroxypropyl methyl cellulose(HPMC K4M)as the hydrating agent.Small piece.According to the results of single-factor experiments,the porogen dosage(X1),the osmotic pressure active substance dosage(X2)and the expansion agent dosage(X3)of the drug-containing layer that have the most significant impact on the in vitro release are selected as the main influencing factors,and the star point design is adopted-The effect surface method was used to perform model fitting,and finally the dosage of porogen(PEG 6000)was 14 mg,the dosage of drugcontaining layer osmotic pressure active substance(NaCl)was 33.7 mg,and the dosage of expansion agent(PEO 8 million)was 33.2 mg.The in vitro cumulative release and the fit of the zero-order equation of the three batches of nimodipine osmotic pump capsules prepared according to this optimal prescription are all greater than 0.997,and the relative deviation between the actual values of Y2,Y6,and Y12 is less than 5%.Shows that this process and prescription are feasible.In the study of release mechanism,the effects of drug release pathway,diffusion mechanism,medium fluid dynamics and pH value on cumulative release were investigated.Thef2value of the drug release route was 14.28,the f2 value of the diffusion mechanism was 21.29,and the f2 value affected by the method,rotation speed,and different pH values were all greater than 50,indicating that the porogen is the drug release pathway and penetrates the active substance.For the drug release power,the osmotic pressure difference between the preparation and the release medium will affect the drug release rate,and the drug release is not affected by the external environment such as pH and gastrointestinal peristalsis.In the stability experiment,nimodipine osmotic pump capsules are relatively stable under high temperature conditions,and its appearance,weight,content and cumulative release degree have no obvious changes.However,it is hygroscopic under high humidity conditions.Under light conditions,the color of the light surface of the drug-containing layer will be slightly darker,and the content and cumulative release will be slightly reduced.Therefore,the preparation needs to be stored in a dark,dry and sealed manner.The nimodipine osmotic pump capsule prepared in this study has a good controlled release effect.The drug release is relatively complete within 12 hours,the cumulative release is greater than 90%,and it is close to the zero-order release equation,achieving the desired effect.