Study On The NM Capsules Of Osmotic Pump Controlled Release With Self-Microemulsifying

NM is a dihydropyridin calcium antagonist which is mainly clinically used for sudden hearing loss, mild or moderate hypertension, ischemic cerebrovascular disease. When NM enters the cerebral tissue, it combines with the recipient of calcium channel reversibly and specially. And it also regulates the calcium to flow into nerve cells and influences the electrical properties of nerve cells and the balance of nerve medium.Because of its poor water solubility and absorption after oral, its clinical therapeutic effect has been limited. Self-microemulsion drug delivery system(SMEDDS) is a kind of new drug delivery system, which has attract great attention in recent years. It has been used as a vehicle to increase the absorption of insoluble drugs to expand its bioavailability. NM was combined to self-microemulsion sustained releasing prepare, which would avoid the fluctuation of serum concentration, reduce the side effects increase and help to improve the absorption and bioavailability.We selected NM as a model drug. The property and solubility of NM in different oil phase was assayed. After making emulsifier and auxiliary emulsifier in different combinations, pseudo-ternary phase diagram were constructed by line up the combination which form the microemulsion. To screen the SMEDDS, we compared the area of self-microemulsifying, the appearance of the microemulsion, the rate of formation of microemulsion. On the basis of the experiment, the final combination is oil phase 1, surfactant 1, ethyl alcohol. Basis on the drug loading capacity, temperature, dilution multiple, types and contents of osmotic promoter, the optimal prescription of SMEDDS was consisted of oil phase 1: surfactant 1:ethyl alcohol=35:50:15(W/W/W). The drug loading capacity is 6%.To combined SMEDDS and osmotic pump, the following experiments were carried out. Release determination method of NM was established, it includes high performance liquid chromatography and ultraviolet spectrophotometry. We mixed the Na Cl as Osmotic promoter 1:1 with the optimal prescription(w/w) and got the capsule core materials. Cellulose acetate(CA), triethyl citrate(TEC) and polyethylene glycol 4000(PEG-4000) were selected as the coating materials and acetone-isopropanol co-solvent is employed as coating medium. In this way, the self-Microemulsifying osmotic pump capsules of NM were prepared. The kinds and dosage of osmotic promoter, TEC, PEG-4000, coating level and the size of the drug release hole were investigated, respectively. The dosage of the auxiliary material was determined. The coating level and the dosage of PEG-400 and size of the drug release hole were optimized by central composite design, having the accumulative release amount in 12h(R1)and the total range of practical and theoretical dissolution of every timing(R2)as the evaluation standard. Three factors were finalized: 3% PEG-4000, 7.5% coating level and 0.7mm drug release hole. The self-made osmotic pump capsules had excellent zero-order release characteristics in the time period of 12 h and the reproducibility of releasing appeared good.