Controlling Nucleation and Fabricating Nanoparticulate Formulation of Sorafenib Using a High-Gravity Rotating Packed Bed

Abstract

Nucleation is the initial step of the crystallization process and is the significant step to prepare nanometer-sized crystalline materials. In this work, we systematically investigated the nucleation kinetics of poorly water-soluble drug sorafenib when precipitated by liquid antisolvent precipitation in high-gravity rotating packed bed. We found that high-gravity field tremendously promoted the nucleation rate, and the nucleation rate was increased by 2–3 orders of magnitude over that in the stirred tank reactor. Moreover, polymer excipients have a significant impact on nucleation; especially, poly­(vinylpyrrolidone) (PVP) could increase the nucleation rate by 3 orders of magnitude over that without excipient. Finally, stable amorphous sorafenib nanoparticulate formulation with a particle size of 80 nm was obtained by controlling nucleation in RPB. Compared to the coarse drug, the nanoparticulate formulation performed faster drug release and had much better cytotoxicity. In vivo pharmacokinetics of the nanoparticulate formulation displayed the increase in plasma concentration time curve (AUC0–∞) and maximum plasma concentration (C max), which demonstrated nanoparticulate formulation could enhance the bioavailability and exhibit extensive potential in the pharmaceutical industry.

Amorphous Nanoparticulate Formulation of Sirolimus and Its Tablets

“…However, when continuing to increase the AS/S FRR from 20 to 30, large flaky drug particles began to appear. This was in agreement with the result reported in our previous work [ 22 ].…”

“…The growth rate of the crystal is inhibited at a high nucleation rate, which promotes the assembly of nanoparticles with a narrow size distribution. The nucleation kinetics of poorly water-soluble drug during the HGAP process were investigated in our previous study [ 22 ]. We found that excipients, high-gravity field and AS/S flow ratio were key factors in influencing nucleation rate, and hence affected particle size [ 22 ].…”

“…The nucleation kinetics of poorly water-soluble drug during the HGAP process were investigated in our previous study [ 22 ]. We found that excipients, high-gravity field and AS/S flow ratio were key factors in influencing nucleation rate, and hence affected particle size [ 22 ]. Therefore, in this work, we firstly screened excipients.…”

Effect of Different Formulation Variables on Release Characteristics of Gastro-Floating Microspheres of Ethyl Cellulose/Carbopol 934p Encapsulating Sorafenib

“…Sorafenib (SFN) is an endorsed drug to treat hepatocellular carcinoma (HCC) [1]. SFN is a multi-kinase inhibitor that prolongs overall survival and postpones the opportunity to progression in patients with advanced HCC who are not candidates for remedial treatment [2]. SFN is a weakly basic drug with a higher absorption rate under acidic conditions in the stomach than in the intestine [3].…”

A review on computational fluid dynamic simulation for rotating packed beds

“…4,5 Therefore, an RPB with a small volume can achieve higher volumetric mass transfer coefficients. 6 Many researchers have proved the advantage of RPBs in absorption, 7,8 desorption, 9 distillation, 10,11 crystallization, 12 production of nanoparticles, 13,14 etc. In addition, there are many successful industrial applications of RPBs.…”