Nim Horizon Slow Release Micro Pill Technology Research

The technology of increasing the solubility and dissolution rate of poorly soluble drug and obtaining the sustained release preparation remains one of the most challenging aspects of modern pharmaceutics. Most studies are in lab-scale.The purpose of this paper were to find a process with industrial prospect to prepare sustained release preparation of poorly soluble drugs. Nimodipine (NMD), which has a very low solubility in vitro, was selected as the model drug to enhance the solubility and dissolution rate by basket milling technique, then sustained-release pellets were prepared by extrution-spheronisation technique.Hot-melt extrusion technique, co-grinding technique and basket milling technique were used to increase the dissolution of NMD, Then matrix sustained release pellets were prepared by extrution-spheronisation technique, respectively. Dissolution results indicated that three techniques can increase the dissolution rate. But hot-melt extrusion and co-grinding technique was difficult to operate when combined with extrution-spheronisation technique.The optimized formulation and process of basket milling mixture and pellets were determined by single factor tests. The formulation of basket miiling mixture was:NMD: 8%HPMC-E5(2:3), milling time was 3 hours, and milling speed was 40Hz. The results of Differential Scanning Calorimeter (DSC) and microscopy tests indicated that NMD retained crystalline state in the basket milling mixture and well dispersed. Particle size of NMD had a reduction. The formulation of NMD sustained release pellets was scaled up to 6000 dosage unit, all of the three batches of pellets exhibited good release profile. The investigation on the drug release mechanisms indicated that the drug release profiles in vitro from sustained-release pellets mainly followed first order equation. Results of stability studies on sustained-release pellets of NMD showed that the pellets were sensitive to light and high humidity.UPLC-MS/MS method was developed to quantify the drug plasma concentration of beagle dogs, and the studies of pharmacokinetics were performed after oral administration of single dose of two formulations. The pharmacokinetic parameters of sustained-release pellets, commercial tablet and commercial sustained release capsule of nimodipine were as below in turn:(987.419±576.962)、(538.535±203.448) and (715.324±464.969) ng/mL·h; Cmax were (174.309±53.486),(114.863±74.504)and(127.688±69.573)ng/mL; Tmax were(4.200±1.789), (2.400±3.190)and(5.000±3.808)h。Compared with commercial tablet and commercial sustained release capsule, the relative bioavailabilities of sustained-release pellets were (199.3±137.3)% and (222.7±161.2)%, respectively.