Qiufang Jing

Characteristics of bicalutamide solid dispersions and improvement of the dissolution

ABSTRACT The purpose of our study was to formulate and evaluate bicalutamide (BL) solid dispersions (SD). The physicochemical properties were evaluated by differential scanning calorimetry (DSC), Fourier-Transform infrared (FT-IR) spectroscopy, Powder X-ray diffractometry (PXRD), dissolution studies, and stability studies. The dissolution studies demonstrated that the dissolution of BL from BL-SD increased with an increase in carrier content (PVP K30). X-ray assays and DSC results both confirmed the amorphous state of BL in BL-SD. Stability studies conducted after 6 months showed that BL exhibited excellent stability in the solid dispersion of PVP K30 (1:5).

Characterization of ibuprofen microparticle and improvement of the dissolution

Abstract The objective of this study was to prepare ibuprofen (IBP) microparticles by pH-change method and enhance the dissolution rate in vitro. Tween80 and Cremophor RH40 were selected as stabilizers to change the microparticles morphology. The microparticles were evaluated by dissolution profiles and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), laser particle size analyzer, scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). IBP microparticle prepared with surfactants showed a significant increase in dissolution rate (more than three times within 10 min) and an obvious decrease in mean particle size. The morphology of microparticles was obviously changed. XRD and DSC results revealed that the crystalline state of the untreated IBP and the prepared IBP microparticles were similar. The crystallinity of microparticles produced might be lightly reduced by adding surfactants in preparation process. All results showed that it was useful to prepare high dispersion microparticle by adding surfactants in the preparation process for improving the dissolution.

Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Anethole Trithione by Combined Use of Surfactants

The characteristics of self-nanoemulsifying drug delivery system (SNEDDS) of Anethole trithione (ATT) for oral administration by the combined use of surfactants were investigated. In combination with surfactants, the SNEDDS provided smaller particle size, more oil loading, and shorter emulsification time. ATT from the SNEDDS rapidly dissolved in dissolution media whereas the ATT tablets showed different dissolution patterns according to the dissolution media. Furthermore, loading of ATT in SNEDDS improved the stability of ATT, and particle size of ATT nanoemulsion generated upon dilution was kept constant both in simulated gastric fluid and simulated intestinal fluid without enzyme.

A mixed solvent system for preparation of spherically agglomerated crystals of ascorbic acid.

Abstract The objective of this research was to develop a novel solvent system to prepare spherically agglomerated crystals (SAC) of ascorbic acid with improved flowability for direct compression. A spherical agglomeration method was developed by selecting the mixed solvents (n-butyl and ethyl acetate) as a poor solvent and the process was further optimized by using triangular phase diagram and particle vision measurement. Physiochemical properties of SAC were characterized and compared with original drug crystals. It showed that amount of poor solvent, ratio of solvent mixture, and drug concentration are critical for preparation of SAC with desirable properties. The solid state of SAC was same as original crystals according to DSC, XRD, and FT-IR results. There was no significant difference in solubility and dissolution rate of drug between SAC and original crystals. The flowability and packability of SAC as well as the tensile strength and elastic recovery of tablets made from SAC were all significantly improved when compared with original crystals and tablets from crystals. It is concluded that the present method was suitable to prepare SAC of ascorbic acid for direct compression.

Synthesis and Characterization of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate-Block-Poly (ε-caprolactone) Copolymer Used as Carriers for Microparticles

A novel copolymer, D-α-tocopheryl polyethylene glycol 1000 succinate-block-Poly (ε-caprolactone) (TPGS-block-PCL), was synthesized and characterized by 1H-NMR and FTIR. The molecular weight was determined by gel permeation chromatography. TPGS-block-PCL can be used to prepare microparticles for drug delivery system by a modified solvent extraction/evaporation method without extra emulsifier. The risperidone-loaded microparticles were characterized by laser light scattering for particle size and by scanning electron microscopy (SEM) for surface morphology. The drug encapsulation efficiency and the in vitro drug release profiles were measured. A significantly higher drug release rate was observed for microparticles with TPGS-block-PCL copolymer than PCL.

Improving the physicochemical properties of bicalutamide by complex formation with bovine serum albumin

Abstract Bicalutamide‐bovine serum albumin (Bic‐BSA) complexes were prepared by anti‐solvent precipitation. Bovine serum albumin (BSA) was used as a stabilizer for particle growth. The physicochemical properties of Bic‐BSA were analyzed by scanning electron microscopy, X‐ray powder diffraction and differential scanning calorimetry. The interaction between Bic and BSA was characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, fluorescence spectroscopy and molecular docking. The particle size could be easily reduced to 1–10 &mgr;m with a good lognormal distribution. The Bic‐BSA complexes exhibited nonporous spherical morphology with a uniformly plicated surface. Moreover, the crystal form and thermostability of Bic were altered in the presence of BSA. Bic was found to make hydrogen bonding and hydrophobic interactions with BSA by spectroscopic studies and molecular docking. Results from the Van’t Hoff equation and binding free energy calculations indicated that the improvement of physicochemical properties was the consequence of a variety of interactions in the Bic‐BSA system. Bic‐BSA tablets showed significantly enhanced dissolution. It was concluded that BSA plays an important role in improving the physicochemical properties of Bic due to strong multiple interactions between Bic and BSA. Graphical abstract Figure. No Caption available.

New self-nanoemulsifying drug delivery system (SNEDDS) with amphiphilic diblock copolymer methoxy poly (ethylene glycol)-block-poly (ϵ-caprolactone)

The objective of the study is to prepare a new self-nanoemulsifying drug delivery system (SNEDDS) with amphiphilic diblock copolymers methoxy poly (ethylene glycol)-block-poly (ϵ-caprolactone) (MPEG-b-PCL) and to investigate the effect of MPEG-b-PCL on the characteristics of SNEDDS. MPEG-b-PCL was synthesized and characterized by 1H-NMR, IR and GPC. Various ratios of MPEG-b-PCL copolymers and Tween 80 were used as emulsifier to prepare the new SNEDDS. SNEDDS with high oil and low surfactant content forms a semi-solid gel at room temperature, which could be effectively sealed in soft or hard capsules. The mean droplet size of SNEDDS-generated nanoemulsions significantly decreased after the addition of diblock polymer and increased with increase of PCL chain in MPEG-b-PCL. The drug Coenzyme Q10 (CoQ10) was chosen as the model compound in this study due to its insolubility in water. CoQ10 from SNEDDS was rapidly dissolved regardless of the fluid condition.

Antisolvent Recrystallization Strategy to Screen Appropriate Carriers to Stabilize Filgotinib Amorphous Solid Dispersions

Drugs in amorphous solid dispersions (ASDs) are highly dispersed in hydrophilic polymeric carriers, which also help to restrain recrystallization and stabilize the ASDs. In this study, microscopic observation after antisolvent recrystallization was developed as a rapid screening method to select appropriate polymers for the initial design filgotinib (FTN) ASDs. Using solvent evaporation, FTN ASDs with the polymers were prepared, and accelerated experimentation validated this screening method. Fourier-transform infrared spectroscopy, Raman scattering, and nuclear magnetic resonance revealed hydrogen-bonding formation in the drug-polymer binary system, which was critical for ASDs stabilization. A Flory-Huggins interaction parameter and water sorption isotherms were applied to evaluate the strength of the interaction between FTN and the polymers. The dissolution rate was also significantly improved by ASDs formulation, and the presence of the polymers exerted solubilization effects. These results suggested the efficacy of this screening method as a preliminary tool for polymer selection in ASDs design.

The Physicochemical Investigation of 17β-Estradiol Crystalline Prepared by In Situ pH-Dependent Solubility Technique with Polyvinylpyrrolidone

ABSTRACTMicro-particles of 17β-estradiol (ED) were prepared with polyvinylpyrrolidone (PVP) by in situ pH-dependent solubility technique. Products were characterized using multiple instruments, and molecular interactions between ED and PVP were explored. Powder X-ray diffraction and thermal analysis revealed crystalline ED in the micro-particles is hemihydrated. PVP was also present in the micro-particles. Laser particle size analysis and scanning electron microscopy revealed thin slice morphology, which might have resulted from the influence of PVP. Moreover, the results of contact angle, specific surface area, and dynamic vapor sorption showed that the surface properties of products were improved. These physicochemical properties of the micro-particles resulted in an obvious improvement in dissolution rate. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance revealed hydrogen bonding between ED and PVP. A method was established for the preparation of micro-particles through the addition of PVP during the reaction process.