The Preparation Of Nefopam Hydrochloride Orally Disintegrating Tablet

Objective: To develop a nefopam hydrochloride orally disintegrating tablet which can be meet midrange and severe pain such as post-operative pain, acute surgically pain, nerve muscle pain and so on.Methods: Prescription and preparation of the tablets were formulated according to the orthogonal design by direct compression.β-cyclodextrin inclusion complex techniques and correctant were evaluated to mask the bitter taste of nefopam hydrochloride. The quality criteria (protocol) and explanation of nefopam hydrochloride orally disintegrating tablet were drafted out according to guiding principles of CP 2005. The stability was investigated through accelerated test. The in vivo behavior of the tablets was evaluated in beagle dogs after administration of orally disintegrating tablets and ordinary tablets in the market by a randomized,crossover and self-control trial. Pharmacokinetic parameters of the two formulations were compared,and the relative bioavailability and bioequivalence were calculated.Results: The optimized formulation was NFH20%,MCC40%,L-HPC5%,PVPP8%, lactose 10%, mannito113.5%, aspartame2%, orange essencel%, magnesium stearate0.5%, and the tablet weight 0.1g(including 20mg NFH). The preparation of nefopam hydrochloride orally disintegrating tablet likes that: Amount of nefopam hydrochloride, manicol, lactose, disintegrants, orange essence, aspartame, magnesium stearate according to every prescription content were accurately weighed, after mixing sufficiently, all the materials were put through 0.3mm screen, direct compressing by 7mm chop-out die after mixing sufficiently, The hardness was about 3N, packaging by aluminium foil and plastic bottles. The trituration method, which was prepared for nefopam hydrochlorideβ-cyclodextrin inclusion complex, was better than solution stirring method and ultrasound method.The recoverable ratio and entrapment efficiency by trituration method were 88.32% and 71.31 %, respectively. In the quality criteria, we used the improved disintegration voltage equipment to determinate disintegrating time. The average disintegrating time was between 20-40 second, the most permission time was 1 minite. The stability of nefopam hydrochloride orally disintegrating tablet was satisfactory. There were no significant change on character disintegrating time and content in months under 40℃±2℃. High performance liquid chromatography (HPLC) was taken to determine the content of nefopam hydrochloride in plasma. The calibration curve of nefopam hydrochloride lined in the concentration range of 5.0-500ng/mL. The pharmacokinetic parameters of orally disintegrating tablets and ordinary tablets in beagle were Cmax: 69.5212±12.556 and 62.5171±20.6340ng/mL, Tmax: 2.5683±0.1879 and 2.612±0.422h, T_1/2 :3.2634±0.9229 and 3.2408±1.4589h, relative bioavailability was 102.7±22.5%.Conclusions: Nefopam hydrochlorideβ-cyclodextrin inclusion complex can mask bitter taste of material,however, it is not suitable for direct compression because of its big volume and poor plastic flow. Eventually theβ-cyclodextrin inclusion complex was not prepared for nefopam hydrochloride orally disintegrating tablet. Compared with the common tablets,the orally disintegrating tablets was bioequivalence. In a word, the nefopam hydrochloride orally disintegrating tablet prepared in this research, which has the advantages of good-tasting, fast-disintegrating, simple preparation and quality-controlled, creates favourable qualification for development of nefopam hydrochloride.