Paliperidone(C23H27FN403), also referred to 9-hydroxy-risperidone, is approved by FDA in 2006 and can be used for the treatment of schizophrenia. The name of its commodity is Ivega. And it is an active metabolite of risperidone, which is an atypical antipsychotic  drug. Pamperidone Palmitate (C39H57FN4O4), which is a kind of prodrug, is a ester synthesized by pamperidone and palmitic acid. Prodrug is a kind of compound which has no activity or has little activity in vitro. By releasing substances with pharmacological activity after the action of enzymes or non-enzymes, it could overcome some shortcomings of the original drug on the basis of maintaining or even enhancing its pesticide effect. Pamperidone palmitate injection is mainly used in the treatment of schizophrenia in acute phase and maintenance phase. It has the effect of rapid onset in acute phase and continuous improvement in symptoms in maintenance phase.

Figure 1 the structural formula of Pamperidone Palmitate

This article will briefly introduce the application of BEE microfluidizer high pressure homogenizer in the preparation of Pamperidone Palmitate nanosuspension.

Equipments：

Electronic analytical balance (BSA124S-CW, Sartorious, Germany);

Ultrasonic cleaning machine (RUC-5200, Shanghai Ruiqi Electronic Equipment Co., Ltd, China);

High-shear dispersion emulsifying machine (F25, FLUKO, America);

Laser particle size analyzer (mastersizer 2000, Malvern Panalytical, UK);

Wet ball mill (Minicer, NETZSCH, Germany);

Microfluidizer high pressure homogenizer (NanoDeBEE, BEE, America).

Reagents and drugs:

Pamperidone Palmitate ; ammonium acetate; NaOH; tween-20; citric acid monohydrate; anhydrous sodium hydrogen phosphate; sodium dihydrogen phosphate monohydrate; polyvinylpyrrolidone K30 (PVP-K30); sodium carboxymethyl cellulose; xanthan gum; polyethylene glycol 4000; ultrapure water; water is ultrapure; methanol, acetonitrile, N, N-dimethylformamide (DMF) is chromatographically pure; tetrahydrofuran (THF) and other reagents are analytically pure.

Experimental steps:

1.Analytical methods: define the best detection wavelength of Pamperidone Palmitate- chromatographic conditions determination- specific validation- standard curve drawing- precision determination- recovery detection- minimum detection limit and minimum quantitative limit detection- inter-industry stability detection  

2.Steps of the detection of factors that influence the preparation of Pamperidone Palmitate nanosuspension by microfluidizer high pressure homogenizer:

1） Detection of the effect of homogenization times on particle size:

Weigh 15.6g PP and disperse it in 80 mL injection water containing 1.2g tween-20. Let them shear at a speed of 20,000 rpm for 15 minutes in an ice bath and then put into NanoDeBEE under the pressure of 30 000 psi. The particle size and particle size distribution index will be measured after 2、4 、8 、12 、16 、20 、24 、28 、32 times.

2） Detection of the effect of homogenization pressure on particle size:

Weigh 15.6g PP and 1.2g tween-20. Disperse tween-20 in 80 mL injection water first and then PP. Let them shear at a speed of 20,000 rpm for 15 minutes in an ice bath and then put into NanoDeBEE. The particle size and particle size distribution index of nanosuspension will be measured after 12 times under the pressure of 20 000 psi and 30000 psi.

Results:

1）Effect of homogenization times on particle size

Figure 2 effect of homogenization times on particle size

Table 1 effect of homogenization times on particle size

2）Effect of homogenization pressure on particle size

Figure 3 effect of homogenization pressure on particle size

Summary

From Figure 2 and Table 1, it can be seen that the particle size decreases with the increase of homogenization times. However, when the number of homogenization times increases to a certain value, the particle size will don’t decrease but increase, which is similar to those reported literatures. Figure 3 shows that the larger the homogenization pressure, the smaller the particle size of the nanosuspension when the homogenization times are the same.

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