| Schizophrenia is a multifaceted disorder sense perception, thinking, feeling, and so uncoordinated behavior and mental activity as the main feature of severe mental illness. Schizophrenia not only caused serious distress to patients and their families, but also seriously disrupted social order, whereby direct or indirect economic losses caused by the disease about 20 to 30 billion dollar each year. Aripiprazole is a new atypical antipsychotic, for the clinical treatment of first-line treatment of schizophrenia. Currently,The market is only ordinary tablets and orally disintegrating tablets. An orally disintegrating tablet system in the mouth that can disintegrate or dissolve tablets without water, easy to use, higher bioavailability and reduce gastrointestinal mucosa irritation for the Schizophrenia patients and other special patients taking.Aripiprazole orally disintegrating tablet is sold in only one enterprise in China, and the stability of commercial formulations is poor that produces a large number of related substances during market life.To provide safe, effective and high quality medicines to meet the needs of the clinical application of drugs for the majority of patients. Therefore,to develop more safe and more effective aripiprazole orally disintegrating tablets is with good market prospects and application value.On the basis of literature review, this paper designed experiment with use of quality by design(QBD).Aripiprazole of the average particle size is 4.426 microns by Malvern Mastersizer 2000 and to study Aripiprazole of solubility under different pH value.To obtain the optimized excipients of formulation by DSC and HPLC, such as Microcrystalline cellulose,mannitol,crospovidone, Croscarmellose sodium, magnesium stearate, Aerosiland aspartame.Second,the formula and process research.The formula optimization by Full-factorial-experiment-design, with the disintegration time, content uniformity, related substances, dissolution, character and taste as evaluation indexes parameters,such as diluent, disintegrating agent, lubricant, glidant,taste masking agent on the effect of orally disintegrating tablets.The final formula optimization:Aripiprazole 5%, Microcrystalline cellulose 30%,mannitol 55%,crospovidone 5%, Croscarmellose sodium 2%, magnesium stearate 1%, Aerosil 1% and aspartame 1%.To study the process parameters by single factor design, such as the mixing time is 5 minutes, total mixing time is 4 minutes, tabletting 20 rpm speed, the main pressure is 15.0 KN.Scale up to validate the formula and process, the results showed that have good reproducibility.Besides,HPLC method was used to determine the assay of Aripiprazole.The detective wavelength was set at 254 nm, the mobile phase consisted of acetonitrile/methanol/water/acetic acid (35:15:50:1, V/V/V/V).The calibration curve of peak area v.s. Concentration of Aripiprazole was A=21441C-28545,R=0.9997(where A: peak area and C:Aripiprazole concentration) with the average recovery of 98.0%-102.0% and RSD is less than 2%. The impurity Ⅰ, impurity Ⅱ and other single impurity should not begreater than 0.2%, and the impurities should not exceed 1.0%.Based on the above conditions, the obtained Aripiprazole was satisfied and met the test standards and the 37th version of United States Pharmacopeia.The stability wase valuated by the traits, the release rate, the related materials and drug content. The study of preliminary stability showed that the orally disintegrating tablet showed stability in sunlight(4500LX±500LX), high temperature(60), high humidify for 10 days, Accelerated testing was carried out under temperature (40±2℃) and RH(75±5)% condition for 6 months,the long-term stability under temperature (25±2℃)and RH (60±10%) condition for 6 months.The results showed that the preparations were stale enough. |
PDF Full Text Request