Preparation of amorphous drug nanoparticles by high-gravity reactive precipitation technique

Zhang, Zhibing; Xie, Miao-Ling; Kuang, Yun-Yun; Wang, Jie‐Xin; Le, Yuan; Zeng, Xiaofei; Chen, Jianfeng

doi:10.1016/j.cep.2016.03.015

Cited by 19 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our present study, free icaritin precipitated when an alkaline solution of icaritin was added dropwise to an acidic solution during vigorous stirring ( Figure 2 a). This process of acid–base precipitation is a type of reactive precipitation [ 9 ]. Therefore, our RPT is suitable for icaritin.…”

Section: Resultsmentioning

confidence: 99%

“…Based on the results of the above experiments, we conclude that our RPT is the alternative method for preparing AINs. In this process, a high degree of supersaturation was generated immediately due to the decreased solubility of icaritin by acid–base neutralization reactions, which results in a fast nucleation rate and ultrafine particles coated with polymers [ 9 ]. Moreover, toxic organic solvents were avoided in the preparation.…”

Section: Resultsmentioning

confidence: 99%

“…A schematic illustration of the co The preparation of amorphous icaritin nanoparticles (AINs) may represent a strategy for enhancing the solubility and bioavailability of icaritin. To date, various methods of preparing nanosized drugs have been reported, including supercritical fluid techniques [7,8], reactive precipitation techniques (RPTs) [9], anti-solvent precipitation methods [10,11], sonoprecipitation methods [7], evaporative precipitation methods [12], as well as media milling and high-pressure homogenization [13]. In order to further improve the solubility and dissolution rates of poorly soluble drugs, inhibition of crystallization to form amorphous particles has also been adopted widely.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preparation, Characterization, and In Vivo Evaluation of Amorphous Icaritin Nanoparticles Prepared by a Reactive Precipitation Technique

Tang

Meng²,

Chen³

et al. 2021

Molecules

View full text Add to dashboard Cite

Icaritin is a promising anti-hepatoma drug that is currently being tested in a phase-III clinical trial. A novel combination of amorphization and nanonization was used to enhance the oral bioavailability of icaritin. Amorphous icaritin nanoparticles (AINs) were prepared by a reactive precipitation technique (RPT). Fourier transform infrared spectrometry was used to investigate the mechanism underlying the formation of amorphous nanoparticles. AINs were characterized via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Our prepared AINs were also evaluated for their dissolution rates in vitro and oral bioavailability. The resultant nanosized AINs (64 nm) were amorphous and exhibited a higher dissolution rate than that derived from a previous oil-suspension formulation. Fourier transform infrared spectroscopy (FTIR) revealed that the C=O groups from the hydrophilic chain of polymers and the OH groups from icaritin formed hydrogen bonds that inhibited AIN crystallization and aggregation. Furthermore, an oral administration assay in beagle dogs showed that Cmax and AUClast of the dried AINs formulation were 3.3-fold and 4.5-fold higher than those of the oil-suspension preparation (p < 0.01), respectively. Our results demonstrate that the preparation of amorphous drug nanoparticles via our RPT may be a promising technique for improving the oral bioavailability of poorly water-soluble drugs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Preparation, Characterization, and In Vivo Evaluation of Amorphous Icaritin Nanoparticles Prepared by a Reactive Precipitation Technique

Tang

Meng²,

Chen³

et al. 2021

Molecules

View full text Add to dashboard Cite

show abstract

“…As the time was short for allowing particle growth, only smaller particles were formed. 23 But when the dropping speed was .4 mL/min, the change in the MPS was not obvious; therefore, the optimum dropping speed was selected as 4 mL/min.…”

Section: Dropping Speedmentioning

confidence: 99%

Preparation of honokiol nanoparticles by liquid antisolvent precipitation technique, characterization, pharmacokinetics, and evaluation of inhibitory effect on HepG2 cells

Wei¹,

Wang²,

Wang³

et al. 2018

IJN

View full text Add to dashboard Cite

BackgroundHonokiol is a bioactive lignanoid and has been utilized in traditional Chinese medicine for a long time. It exhibits several pharmacological properties, such as anticancer effects, anti-inflammatory effects, and antianxiety effects. However, the poor aqueous solubility of honokiol has impeded clinical applications.Materials and methodsIn the present study, we adopted the liquid antisolvent precipitation (LAP) technique to prepare nanoparticles of honokiol for enhancement of solubility and bioavailability. Moreover, the honokiol nanoparticles obtained were investigated and evaluated in terms of morphology, physicochemical properties, saturation solubility, dissolution in vitro, bioavailability in vivo, toxicity, and the inhibitory effect on growth of HepG2 cells.ResultsThe obtained honokiol nanoparticles existed nearly in spherical shape and could be turned into amorphous structure by the LAP method. Moreover, the solubility of the honokiol nanoparticles was extremely higher than that of free honokiol, and the nanoparticle dissolution rate was also higher than that of free honokiol, which was about 20.41 times and 26.2 times than that of free honokiol in artificial gastric juice and in artificial intestinal juice. The area under the curve [AUC(0–t)] value of honokiol nanoparticles was about 6.52 times greater than that of free honokiol; therefore, the honokiol nanoparticles had a higher bioavailability than free honokiol but were innoxious to the organs of rats. Additionally, the honokiol nanoparticles exhibited a higher inhibition of HepG2 cells due to their lower IC50 compared to free honokiol.ConclusionHonokiol nanoparticles have high solubility and bioavailability, and can become a new oral drug formulation and produce a better response for its clinical applications.

show abstract

“…The very low aqueous solubility of CEF contributes to its low a from the gastrointestinal tract [13] and makes it difficult the deve formulations. Several efforts have been performed to overcome this im including preparation of CEF amorphous nanoparticles [14,15] different coformers [16], as well as the use of solid dispersions with d carriers [17][18][19] or of cyclodextrins, alone or in combination with other Moreover, the impact of the above manipulations on the drug bioavailability is often unknown, and these extemporaneous formulations can have limited and unknown physical, chemical and microbiological stability, leading to enhanced risks of medication errors, and the appearance of adverse reactions [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use

et al. 2021

View full text Add to dashboard Cite

Cefixime (CEF) is a cephalosporin included in the WHO Model List of Essential Medicines for Children. Liquid formulations are considered the best choice for pediatric use, due to their great ease of administration and dose-adaptability. Owing to its very low aqueous solubility and poor stability, CEF is only available as a powder for oral suspensions, which can lead to reduced compliance by children, due to its unpleasant texture and taste, and possible non-homogeneous dosage. The aim of this work was to develop an oral pediatric CEF solution endowed with good palatability, exploiting the solubilizing and taste-masking properties of cyclodextrins (CDs), joined to the use of amino acids as an auxiliary third component. Solubility studies indicated sulfobutylether-β-cyclodextrin (SBEβCD) and Histidine (His) as the most effective CD and amino acid, respectively, even though no synergistic effect on drug solubility improvement by their combined use was found. Molecular Dynamic and 1H-NMR studies provided insight into the interactions of binary CEF:His and ternary CEF:His:SBEβCD systems used to prepare CEF solutions, which resulted stable and maintained unchanged antimicrobial activity during the two-weeks-use in therapy. The ternary solution was superior in terms of more tolerable pH (5.6 vs. 4.7) and better palatability, being resulted completely odorless by a panel test.

show abstract

Preparation of amorphous drug nanoparticles by high-gravity reactive precipitation technique

Cited by 19 publications

References 36 publications

Preparation, Characterization, and In Vivo Evaluation of Amorphous Icaritin Nanoparticles Prepared by a Reactive Precipitation Technique

Preparation, Characterization, and In Vivo Evaluation of Amorphous Icaritin Nanoparticles Prepared by a Reactive Precipitation Technique

Preparation of honokiol nanoparticles by liquid antisolvent precipitation technique, characterization, pharmacokinetics, and evaluation of inhibitory effect on HepG2 cells

Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use

Contact Info

Product

Resources

About