Studies On Taste-Masked Orally Disintegrating Tablets

Backgrand and Objective: Recently, A new pharmaceutical dosage form, orally disintegrating tablets (ODT) which can disintegrate rapidly(15-30s) in the oral cavity without drinking water, has attracted the interests of many researchers. This type of tablets offers the advantage of taking with ease, disintegrating quickly, good compliance of patients. But its development was limited by the unpleasant taste of the drugs. So, we selected the berberine hydrochloride (Ber), a drug with strong bitter as the model drug, Its bitter taste was coated by spraying with Eudragit E100 using a fluidized bed. Then, with the coated microcapsule and super-disintegrant prepared the taste-masked Ber-ODT, and evaluated it in vivo and vitro. Methods: 1. Designed suitable methods to value the water absorbtion and the disintegration time of ODT. Selected the super-disintegrant by studying the water uptake rate constant(k), the lag time of water uptake(t₀) , the wetting time and the disintegration time. Through the orthogonal experiment design, selected the basic formulation of ODT by studying the content of super-disintegrant, the content of MCC and the consistency of the tablets. 2. To improve the taste of Ber, we prepared the Ber microcapsules. First, the powders of Ber was granulated using a 3% HPMC solution by a side-spray fluidized bed, and the orthogonal experiment design was used to optimized the process condition. Then, the Ber microcapsules were prepared through coating the Ber microparticles with Eudragit E100 using a bottom-spay fluidized bed. 3. Based on the optimum basic formulation, we compressed the taste-masked Ber-ODT with the Ber microcapsules. Then we tested its taste, disintegration time, and the dissolution curve in 0.1mol/L Hcl, etc. we also studied its stability. 4. Evaluate the bioequaliance of the the taste-masked Ber ODT and the common tablets through studing the pharmacokinetic in rabbits. Results: 1. Through studying the water uptake rate constant, the lag time of water uptake (t₀) , the wetting time and the disintegration time, we selected the most excellent disintegrant was PVPP. From the orthogonal experiment design, we got the best basic formulation of ODT: PVPP 6%, MCC 15%, consistency of tablets 1.5 kg. 2. Using the size distribution of the Ber microparticles as the criterion, the orthogonal experiment design optimized the side-spay parameters were: the spray pressure was 0.1MPa; the spraying rate was 4ml/min; and the bed temperature was 50 ℃ . The produced particles were round and sturdy, D50 is 105μm, it was very suit to be coated. The optimized bottom-spray parameters of preparing Ber microcapsules were : the spray pressure was 0.1MPa; the spraying rate was 3.6⁶.4ml·min^-1; the bed temperature was 35⁴5 ℃. The mass addition of coating material is 80%. The microcapsules we got had a even surface and regular round shape, D₅₀ is 145μm. The light micrographs and the scanning electron micrographs showed that a homogeneous and dense layer was formed over the entire surface of Ber microparticles. The drug content of microcapsules is 55%. Dissolve 55% within 5min, and more than 80% within 45min in 0.1mol/L HCl; but less than 1% in distilled water. These results explained that the Ber microparticles we prepare can mask taste in oral cavity but release drug in stomach. 3. Based on the optimum basic formulation, were prepared thetaste-masked Ber-ODT with Ber microcapsules, the disintegrate time in vitro of it is about 20s, the disintegrate time in oral cavity is less 30s. The taste is good , no person feeled the bitter taste.The ODT we prepared dissolve more than 50% within 5min in 0.1mol/L HCl, faster than common tablets;and more than 80% within 45min,similar to the common tablets. Resultes of the stability tests showed that, the tablets were stabe to light, high temperature, but unstable to high humidity. So, they should be tightly closed. 4. The pharmacokinetic study in rabbits showed that AUC_(0-24), Cmax and T_max had no significant difference between the taste-masked Ber-ODT and the co...