Study On Paliperidone Palmitate Suspension Injection For Three Months

Paliperidone Palmitate Suspension Injection is a long-acting antipsychotic injection developed by Janssen Company.Compared with the paliperidone palmitate suspension injection that is injected once a month,the three-month suspension injection can reduce the frequency of administration and improve patient compliance.At present,there is no suspension injection with a validity period of three months on the market in China.This topic is to study the imitation of its original preparation.The effect of recrystallization process on the particle size and purity of PP ester was studied.The final determination of the process conditions for PP ester recrystallization through single factor experiment is:PP ester:absolute ethanol=1:8（m/v）,stirring speed is40 rpm,cooling rate is 0.1℃/min,and crystallization retention temperature is 30℃.Three batches of continuous recrystallization,The average particle size of PP ester D90 is119μm,average particle size distribution index is 0.33,particle size distribution is relatively uniform,the average purity of is 99.81%,indicating that the process is stable and product quality is reliable.The suspension was prepared by the media grinding method,and the preferred formulation of the suspension is determined to be:main drug PP ester 30%（w/v）,wetting agent Tween-20 0.8%（w/v）,suspending agent PEG4000 3.5%（w/v）,preservative citric acid（monohydrate）0.5%（w/v）,isotonic agent sodium dihydrogen phosphate（monohydrate）0.65%（w/v）,p H regulator Na OH 0.5%（w/v）;The preferred process is:the grinding speed is 200 rpm,the grinding time is 40 min,the diameter of zirconium beads is1.2 mm,and the amount of zirconium beads is 4 m L/100 m L grinding jar.Three batches were prepared repeatedly and the quality was tested.The average particle size D90 is24.31μm,and the surface morphology is an irregular rod-like structure,indicating that the preparation process is stable and the reproducibility is good.The quality of three batches of self-made suspension was studied and compared with the original formulation.The resuspension and needle aspiration are good,and the average p H is 6.94.The in vitro release rate reaches more than 80%of the labeled amount at 23 h,which is compared with the original formulation,The f₂ values of the three batches of release curves are 75.62,74.71,75.32,and all meet the requirement of greater than 50.The measured average content is 96.94%,which is between 95.0%～110.0%of the labeled amount.The maximum single impurity of related substances is 0.13%,and the maximum total impurity is 0.32%,which meets the requirements.The methodological verification of the detection method and the content determination method of the released liquid phase of the suspension liquid is carried out,and all the tests meet the requirements.Stability tests indicate that the suspension should be stored below 30℃and protected from light.The research of this subject has achieved the expected goal.