Study On Combined-release Mini-tablets Capsule Of Carbamazepine

Oral sustained-release and controlled-release solid dosage forms are focuses for researchers in the pharmaceutical field. The objective of this work was to develop a novel multifunctional and multiple unit system, which consists of a variety of mini-tablets with different dosages and combinations by enclosing into a hard gelatin capsule. Carbamazepine (CBZ) was one of the most potent antiepileptic drugs widely used for treatment of simple and complex partial seizures, trigeminal neuralgia, and bipolar affective disorder. In the present study, using CBZ as a model drug, a quick/slow/quick DDS which consists of rapid-release mini-tablets,sustained-release mini-tablets and pulsatile mini-tablets was developed.In the study, ultraviolet spectrophotometry (UV) method was used for in vitro assay ofcarbamazepine during the studies of content and release. Physical and chemical properties of carbamazepine such as equilibrium solubility, stability of aqueous solution and apparent oil-water partition coefficient were investigated.Absorption kinetics and the absorption mechanism of carbamazepine in rat's intestine were studied utilizing in situ perfusion by investigating the effect of intestine segments, drug concentrations of circulating solution on the absorption. The results indicated that the absorption of carbamazepine in rats' intestine was via passive diffusion with a one-order mechanism.Carbanazepine rapid-release mini-tablet formulation was scanned by similar factor method. Preparation technologies and release conditions affecting the release of the mini-tablet were studied.To optimize carbamazepine sustained-release mini-tablet formulation, two critical factors, content of hydroxypropylmethylcellulose (HPMC) and content of ethyl cellulose (EC), influenced greatly the release behavior. With the accumulative percentages of carbamazepine as indices, central composite design was used to optimize these two screened factors.Carbamazepine pulsatile mini-tablet was prepared by the film coating method, Eudragit(?)RS 30D was used as the coating material. The factors of the effect on the drug release including coating level, anti-tacking agents, pore-forming reagent and the amount of CMS-Na were investigated. Orthogonal design was used to optimize the coating formulation and the best optimized range was also obtained.