| Paliperidone osmotic pump tablets are developed and produced by Johnson&Johnson in the United States.It is an oral sustained and controlled release preparation for the treatment of schizophrenia.The dosage form has zero-level drug release,is not easily affected by variable factors in the gastrointestinal tract,and improves the convenience of medication for patients.The original research formulation is a three-layer tablet core and two-hole drug release,the preparation process is complicated,and the equipment requirements are high.This subject intends to prepare a double-layer and dual-release drug pore osmotic pump tablet,and the in vitro release behavior should be consistent with the original formulation.The main drug,paliperidone,is a water-insoluble,weakly basic drug,with an average particle size D50 is 22.19μm.Refered to the prescription information of double-layer osmotic pump tablets,determined the types and limits of excipients.The appearance of the sample under high temperature,high humidity,and light conditions has no obvious change,the content is slightly reduced,and the compatibility is good.A double-layer tablet core is prepared by a wet granulation process,and the tablet core is double-coated.Single-factor experiments were conducted to investigate the influence of the formulation process factors such as the weight gain of the coating film,the amount of penetration enhancing polymer,and the concentration of the coating solution on the drug release.Drug-containing layer prescription:PEO 200K 92 mg,sodium chloride(powder)18.75 mg,PVP K29 7.3 mg,stearic acid(powder)0.75 mg,BHT 0.1 mg,yellow iron oxide 0.1 mg;promotion layer prescription:PEO 7000K 96.65mg,sodium chloride(powder)18.75 mg,PVP K29 7.5 mg,stearic acid(powder)0.75 mg,BHT 0.1 mg,red iron oxide 1.25 mg.Using hydroxyethylcellulose and PEG3350 as packaging materials to prepare the inner coating layer,the weight gain of the coating is0.6%;using CA and PEG3350 as packaging materials to prepare the drug release rate control layer,the coating process parameters:inlet air temperature 30℃,material temperature 27℃,atomization pressure 0.11～0.13 Mpa,coating solution concentration3%～4%,coating weight gain 20%.Three batches of samples were repeatedly tested for quality,and the content was95%～105%,the content of impurity A was less than 1%,and other single maximum impurities were less than 0.2%,the total impurities are less than 1.2%,and the release degree corresponding to each sampling point meets the standard.It is required that the f2value of the release curve is greater than 50,and the moisture content is 1.48%～1.52%(less than 3%).The methodological verification of the content liquid phase analysis method is carried out.The results showed that the standard curve equation in the concentration range of 0.3～30μg/m L is y=436452.68388x-40054.79399,R~2=0.99981>0.99,and the specificity,precision,recovery rate are all meet the requirements.Stability test studies have shown that the appearance content of paliperidone osmotic pump tablets has no significant change,the difference between samples is small,the impurity content is less than 1%,the total impurities are less than 1.2%,the quality is stable,and it needs to be protected from moisture,light,and sealed.The research of this subject has achieved the expected goal. |
