Conventional Solvent Evaporation Method Research Articles

Concurrently Improving both Mechanical and Electrochemical Performances of Quasi-Solid-State Electrical Double-Layer Capacitors by a Rational Design of Gel Polymer Electrolytes.

Aqueous poly(vinyl alcohol) (PVA) gel electrolyte-based quasi-solid-state electrical double-layer capacitors (QSEDLCs) have been extensively investigated in the past ten years, but challenges remain to fabricate the PVA gel electrolyte possessing both superior mechanical and outstanding electrochemical performances. Herein, we develop a strategy to address this issue by a rational design of PVA gel electrolytes, based on a combination of the freeze-thaw (FT) method and sodium perchlorate (NaClO4)-based water-in-salt (WIS) electrolyte. Our study demonstrates that either the FT method or the NaClO4-based WIS electrolyte can improve both the mechanical performance of the PVA gel electrolyte by increasing the crystallization of PVA chains and the electrochemical performance of the PVA gel electrolyte-based QSEDLC by different mechanisms. In comparison with the conventional solvent evaporation method, this work provides an effective strategy to concurrently improve both the mechanical and electrochemical performances of aqueous QSEDLCs.

Development and Evaluation of Antifungal Efficacy of Ketoconazole Pharmacosome

Pharmacosomes are neutral colloidal, lipid vesicular drug delivery system having both negative & positive charge that enhance the bioavailability of drugs by enhacing their solubility both in aqueous as well as non-aqueous phase, additionally reduce gastrointestinal toxicity of drug. Ketoconazole is an imidazole derivative agent which is used both in the treatment of topical or systematic fungal infections with fungi static activity against dermatophytes, yeasts and other pathogenic fungi. Ketoconazole is Biopharmaceutical classification system (BCS) class II drugs that display pH dependent dissolution and absorption. In this present research work Pharmacosome of Ketoconazole was prepared in different ratios of Ketoconazole-PC complex (1:1, 1:1.5 and1:2) using conventional solvent evaporation method. FT-IR spectra showed no significant untoward interaction, Vesicles shape and morphology was carried out with Phase contrast microscopy (PCM) and Scanning electron microscopy (SEM), In-vitro permeation study and anti-fungal activity were duly examined. Drug content in the formulations (1:1) (1:1.5) and (1:2) were found 92.5%, 94.3% and 89.7% respectively. FT-IR conformed proper formation of drug- Pharmaosome complex. Particle size distribution were found to be regular and of spherical shape. In-vitro permeation study showed 78.03%, 89.05% and 55.27% drug release as per respectively formulations (KTP1, KTP2 and KTP3). Pharmacosomes of ketoconazole show improvement in antifungal activity than ketoconazole (Pure).

Injectable sustained-release poly(lactic-co-glycolic acid) (PLGA) microspheres of exenatide prepared by supercritical fluid extraction of emulsion process based on a design of experiment approach.

This study aimed to develop an improved sustained-release (SR) PLGA microsphere of exenatide using supercritical fluid extraction of emulsions (SFEE). As a translational research, we investigated the effect of various process parameters on the fabrication of exenatide-loaded PLGA microspheres by SFEE (ELPM_SFEE) using the Box-Behnken design (BBD), a design of experiment approach. Further, ELPM obtained under optimized conditions and satisfying all the response criteria were compared with PLGA microspheres prepared using the conventional solvent evaporation (ELPM_SE) method through various solid-state characterizations and in vitro and in vivo evaluations. The four process parameters selected as independent variables were pressure (X 1), temperature (X 2), stirring rate (X 3), and flow ratio (X 4). The effects of these independent variables on five responses, namely the particle size, its distribution (SPAN value), encapsulation efficiency (EE), initial drug burst release (IBR), and residual organic solvent, were evaluated using BBD. Based on the experimental results, a desirable range of combinations of various variables in the SFEE process was determined by graphical optimization. Solid-state characterization and in vitro evaluation revealed that ELPM_SFEE improved properties, including a smaller particle size and SPAN value, higher EE, lower IBR, and lower residual solvent. Furthermore, the pharmacokinetic and pharmacodynamic study results indicated better in vivo efficacy with desirable SR properties, including a reduction in blood glucose levels, weight gain, and food intake, for ELPM_SFEE than those generated using SE. Therefore, the potential drawback of conventional technologies such as the SE for the preparation of injectable SR PLGA microspheres could be improved by optimizing the SFEE process.

A COMPARATIVE STUDY OF SOLUBILITY ENHANCEMENT OF BICALUTAMIDE BY SOLID LIPID NANOPARTICLES AND SOLID DISPERSION TECHNIQUE

A comparative evaluation of solid lipid nanoparticles and solid dispersion of bicalutamide using PVP K30 and stearic acid was performed. Bicalutamide solid dispersions (BL- SD) were prepared with conventional solvent evaporation method and bicalutamide solid lipid nanoparticles (BL-SLN) were prepared by precipitation method. The formulations were assessed on the standard evaluation parameters. The study demonstrated that BL-SLN was performed better as compared to (BL- SD).

Influence of l-Lysine-doped Tartaric Acid–Potassium Bromide single crystals: growth and characterization of photonic applications

The effect of l-lysine-doped tartaric acid–potassium bromide (LYTAPB) single crystals has been successfully crystallized by employing conventional slow solvent evaporation method. The lattice unit cell dimensions are valued by single environment crystal X-ray diffraction analysis. The functional groups and spectral properties of the LYTAPB crystal were accredited by FTIR spectral investigation. The linear optical characteristics of the LYTAPB crystal is observed by UV–Vis spectral studied. It has been observed that the load differs linearly through the hardness value. The mechanical stability is measured through the Vickers hardness. Through NLO analysis, the LYTAPB crystal is found to be a phase matchable single crystal and is good transmittance to approve the lower cutoff wavelength district. Second harmonic generation optical susceptibility of the LYTAPB crystal has been verified by Nd:YAG laser technique. Optical limiting achievement of the LYTAPB crystal is established significant wavelength of 1064 nm to possessing SHG efficiency of 1.3 times greater than that of KDP. Hence, it can use the potential material to the frequency–repetition effect of the grown crystals for solid-state photonic materials.

Exosome-modified PLGA Microspheres for Improved Internalization into Dendritic Cells and Macrophages

Considering the significance of effective antigen presentation for boosting immune responses, it is essential to develop delivery systems for antigen presenting cells (APCs; dendritic cells and macrophages). As a simple and facile way for improving delivery efficiency of PLGA microspheres (MS) into APCs, we fabricated exosome-conjugated PLGA MS via polydopamine coating in this study. Spherical micro-sized particles were first prepared by conventional water-in oil-in water (W1/O/W2) double emulsion and solvent evaporation methods and were observed by scanning electron microscopy (SEM). With increasing model protein (ovalbumin)/MS weight ratios, higher amounts of ovalbumin (OVA) were immobilized onto MS. After exosome (EXO) conjugation to MS via polydopamine coating, the amount of nitrogen was significantly increased on the surface of MS, indicating that EXO were successfully conjugated onto MS. EXO-coated dopamine MS (EXO-Dopa MS) exhibited significantly improved delivery into DC2.4 cells and RAW264.7 cells, compared with bare MS and Dopa MS. Therefore, EXO-Dopa MS could be used as effective carriers of immune stimulating biomolecules into APCs for cancer immunotherapy.

Improvement of the dissolution rate and bioavailability of fenofibrate by the supercritical anti-solvent process

The purpose of this study was to improve solubility and oral bioavailability of fenofibrate via solid dispersion (SD) using a supercritical anti-solvent (SAS) process with amphipathic polymers P407 and TPGS. Solid dispersion techniques have been widely used to enhance the solubility and dissolution profiles of poorly soluble drugs. Fenofibrate is classified as a Biopharmaceutics Classification System class II compound because of its low solubility and high gastrointestinal permeability. Two copolymers were selected based on solubility and dissolution tests. Their physicochemical properties were compared with those prepared by conventional solvent evaporation (CSE). The SD formulations containing fenofibrate were successfully prepared using the SAS and CSE methods. The dissolution rate (%) of fenofibrate at 60 min was significantly improved compared with the solution of raw fenofibrate (19.5% ± 3.7%) by 95.1% ± 2.5% and 93.7% ± 4.1% using the SAS and the CSE process, respectively. This approximately four-fold increase in dissolution rate indicates that oral bioavailability can be enhanced. In addition, pharmacokinetic study was analyzed using the area under the curve (AUC) and Cmax values of SAS-SD and CSE-SD in rats. The AUC was 2.1 times higher and Cmax was 1.9 times higher in SAS-SD, indicating higher concentrations of fenofibrate in the blood. In a pharmacodynamic study to evaluate the efficacy of the drug in hyperlipidemic rat models, SAS-SD showed strong lipid-lowering effects including cholesterol (1.9-fold) and triglycerides (3.3-fold), than CSE-SD. Taken together, these results suggested that SAS-SD has excellent potential as a formulation for the poorly soluble drug fenofibrate.

Crystal growth, physical properties and computational insights of semi-organic non-linear optical crystal diphenylguanidinium perchlorate grown by conventional solvent evaporation method

A splendid nonlinear optical single crystals diphenylguanidinium perchlorate (DPGP) was lucratively grown by low cost solvent evaporation method with the dimensions of 8 × 4 × 2 mm3. Structural and morphological studies of grown crystal were confirmed using X-ray diffraction studies. The presence of diverse functional groups was identified using FTIR and RAMAN studies. The molecular structure of a grown crystal was inveterate by NMR studies. The optical transmittance of DPGP crystal was analyzed using UV–vis-NIR studies. Photoluminescence spectrum shows sharp, well defined emission peak at 388 nm. Thermal studies assign that adduct is stable with the melting point of 164 °C. Microhardness studies declare that DPGP crystal belongs to the soft material class and their yield strength and elastic stiffness constant values were evaluated. Photoconductivity studies revealed the negative photoconductive nature of DPGP crystal. Second harmonic generation (SHG) efficiency of the DPGP crystal was 1.4 times that of potassium dihydrogen phosphate. Etching studies were carried out for different etching time. The dielectric studies were performed at different frequency. Laser damage threshold properties of DPGP crystal were examined using Nd:YAG laser system. The HOMO-LUMO energy gap evident the charge transfer interaction of the molecule. The calculated first order hyperpolarizability value is 5 times greater than that of urea. Thus, the grown DPGP single crystals are well suited for NLO device fabrications.

Preparation of Gefitinib Loaded Polycaprolactone Microcapsule For Controlled Release Drug Delivery System

The aim of the study was to prepare gefitinib-loaded polycaprolactone microcapsules by simple conventional solvent evaporation method with a view to achieve controlled release of the drug following subcutaneous administration once in a week for targeted therapeutic action especially locally. The microcapsules were prepared using different drug-polymer ratios (1:2, 1:4 and 1:6) and three different stabilizers/surfactants (0.25% w/v, 0.50% w/v and 0.75% w/v) concentrations in aqueous phase. Depending upon the formulation variables, the highest drug entrapment efficiency and the lowest average particle size diameter of the microcapsules were found to be respectively 90.19±2.61 % and 201±3.05 µ. Comparison of Fourier Transform Infra Red spectra of gefitinib, polycaprolactone, their physical mixture and the drug- loaded microcapsules showed the absence of drug -polymer interaction .The in-vitro dissolution study showed that the release of drug from the microcapsules was almost complete on day seventh and the drug release followed Higuchi model.

Drug loaded nanoparticle coating on totally bioresorbable PLLA stents to prevent in-stent restenosis.

Biodegradable polymer poly (dl-lactide) (PDLLA) has been used as drug coating material for drug-eluting stents due to its excellent biocompatibility and sustained drug release ability. However, the uniform thin layer drug eluting coating on a stent not only inhibits the blood vessel's smooth muscle cell overgrowth but also delay the endotheliation process which is often associated with the occurrence of acute thrombosis. Therefore, in this study, we developed a novel coating method using PDLLA nanoparticles (NPs) as a coating to overcome this issue. The average 300 nm sized sirolimus-loaded PDLLA nanoparticles were prepared by a conventional emulsion solvent evaporation method. A low temperature plasma polymerization technology to graft hydrophilic polymers on to poly (l-lactide) stent was used to increase the surface coating efficiency of nanoparticles on the stent. Results showed that sirolimus-loaded nanoparticles can be successfully coated on to the stents with sustained drug release properties. In vitro cell culture study showed the drug loaded nanoparticle coating effectively inhibited the proliferation of smooth muscle cells while still allowed a faster proliferation of endothelial cells, suggesting that the new NP coated bioresorbable stents have the potential to reduce both the occurrence of in-stent restenosis and acute thrombosis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 88-95, 2018.

Enhanced Dissolution Rate of Dronedarone Hydrochloride via Preparation of Solid Dispersion using Vinylpyrrolidone‐Vinyl Acetate Copolymer (Kollidone® VA 64)

Solid dispersion (SD) systems have been widely used to increase the dissolution rate and oral absorption of poorly water‐soluble compounds. In order to enhance the dissolution rate of dronedarone hydrochloride (DRN), a recent antiarrhythmic agent, SDs of DRN were formulated using conventional solvent evaporation method with amorphous polymers including hydroxypropyl methyl cellulose (HPMC), poly(vinyl pyrrolidone) (PVP), and vinylpyrrolidone‐vinyl acetate copolymer (VA64). The prepared SDs were characterized in terms of drug crystallinity, morphology, and in vitro dissolution profile in aqueous medium. The physical characterization using differential scanning calorimetry and X‐ray powder diffraction revealed that the active compound was molecularly dispersed in all polymeric carriers tested, in a stable amorphous form in drug to polymer ratios ranging from 1:0.5 to 1:2. The dissolution rates of DRN in all SDs were much higher than those from the corresponding physical mixture and drug powder alone. In particular, the greatest dissolution enhancement was obtained from the VA64‐based SD in a drug to polymer weight ratio of 1:1, achieving almost complete drug release after 120 min at pH 1.2. Thus, VA64‐based SD with higher drug dissolution rate along with a simple preparation process is suggested as an alternative for the oral formulation of the benzofuran derivative.

Dissolution and solid state behaviours of carbamazepine-gluconolactone solid dispersion powders: The potential use of gluconolactone as dissolution enhancer

Solid dispersions are one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however, this is reliant on the selection of a suitable carrier and solvent. The present study is the mechanistic evaluation of the changes in polymorphic form of carbamazepine when the type of solvent and the concentration of d-gluconolactone (d-GL) change. The studies reported herein also explore the use of d-GL as a potential hydrophilic carrier to improve the dissolution rate of a poorly water-soluble drug, carbamazepine (CBZ), from physical mixtures and solid dispersion formulations. The effect of using different solvents in the preparation of solid dispersion formulations was also investigated. Different ratios of solid dispersions of the drug and d-GL were prepared using a conventional solvent evaporation method. Different solvents (ethanol, acetone and water) were used as a second experimental variable in the preparation of solid dispersions. Physical mixtures of CBZ and d-GL were also prepared for comparison. The results showed that the presence of d-GL can increase the dissolution rate of CBZ compared to pure CBZ. This study showed that d-GL could be used as a new carrier in solid dispersion formulations and physical mixtures. The interesting solid state behaviour of CBZ in all solid dispersions in the presence of d-GL was fully analyzed using Fourier-transform infrared (FT-IR), X-ray powder diffraction (XRPD), scanning electron microscope (SEM), hot stage microscopy (HSM) and differential scanning calorimetry (DSC). The results showed that depending on the type of solvent and concentration of d-GL used in the preparation of solid dispersions different forms of CBZ (Form I, Form III and dihydrate) can be existed in the formulations.

Preparation and characterization of celecoxib dispersions in soluplus(®): comparison of spray drying and conventional methods.

The present study deals with characterization of dispersions of a poorly water-soluble drug, celecoxib (CLX) in polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®) (SOL)) prepared by different techniques. Dispersions of CLX in SOL at different ratios (2:1, 1:1, 1:2, 1:4 and 1:6) were prepared by spray drying, conventional solvent evaporation and melting methods. The solid states of samples were characterized using particle size measurements, optical and scanning electron microscopy, XRPD, DSC and FT-IR. The Gordon-Taylor equation was used to predict the Tg of samples and the possibility of interaction between CLX and SOL. The solubility and dissolution rate of all samples were determined. Stability of samples was studied at ambient conditions for a period of 12 months. DSC and XRPD analyses confirmed amorphous state of drug in samples. Surprisingly dispersions of CLX:SOL with the ratio of 2:1 and 1:1 showed slower dissolution rate than CLX while other samples showed higher dissolution rate. At 1:2 ratio the spray dried samples exhibited higher dissolution rate than corresponding samples prepared by other methods. However at higher SOL content (1:4 and 1:6), samples prepared by different methods showed similar dissolution profiles. The stability studies showed that there were no remarkable changes in the dissolution profiles and solid state of the drug after 12 months storage at ambient conditions. It was concluded that SOL was a proper carrier to enhance the dissolution rate of CLX. At high SOL ratios the method of preparation of dispersed samples had no effect on dissolution rate, whilst at low SOL content spray drying was more efficient method.

The dissolution enhancement of piroxicam in its physical mixtures and solid dispersion formulations using gluconolactone and glucosamine hydrochloride as potential carriers

The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.

Diaqua-bis-(benzoato-κO)bis-[4,4,5,5-tetra-methyl-2-(pyridin-4-yl-κN)imidazoline-1-oxyl 3-oxide]cobalt(II).

The title compound, [Co(C7H5O2)2(C12H16N3O2)2(H2O)2], was obtained from a conventional solvent evaporation method. The complex mol­ecule is centrosymmetric, so pairs of equivalent ligands lie trans to each other in a slightly distorted octa­hedral CoN2O4 geometry. The CoII ion is coordinated by the pyridine N atoms from NITpPy ligands [NITpPy is 4,4,5,5-tetra­methyl-2-(pyridin-4-yl)imidazoline-1-oxyl 3-oxide), water O atoms and two monodentate benzoate O atoms. The complex mol­ecules are connected by O—H⋯O hydrogen bonds between water mol­ecules and benzoate ligands, forming chains parallel to [100]. π–π stacking inter­actions between the benzoate ligands with centroid–centroid distances of 3.752 (2) Å connect the chains into layers parallel to (10-1).

Preparation of Carboxymethylchitosan Nanoparticles with Acid-Sensitive Bond Based on Solid Dispersion of 10-Hydroxycamptothecin

Solid dispersions were prepared by a conventional solvent evaporation method from the water-insoluble model drug 10-hydroxycamptothecin (HCPT) and monomethoxypoly(ethylene glycol) 2000 (mPEG 2000). And then one type of novel biodegradable nanoparticles, the solid dispersion (HCPT/mPEG-CHO) grafted with carboxymethylchitosan (HCPT/mPEG-g-CMCTS) was synthesized. The increase in HCPT solubility of solid dispersion was up to 21-fold compared with the original drug. With the increasing of the amount of mPEG-CHO, solubility of HCPT was from 7.71 μg/mL to 25.82 μg/mL. Colloid systems based on solid dispersion were stable in aqueous medium at 5°C. After 5 months storage at 25°C, the solid dispersions do not change at all. HCPT/mPEG-g-CMCTS was synthesized by grafting reaction of carboxymethylchitosan with mPEG-CHO to form Schiff base which is sensitive to acid environment. The release rate of HCPT from this conjugate in pH 5.4 was much higher than that in the environment of pH 7.4 and p H 4.5. The cumulative release percentages are 45%, 25%, and 15%, respectively. The cumulative release percentage of HCPT in conjugate was only 15% within 85 h while the original drug was up to 70% in pH 7.4, showing a significant slow-release property. This drug model can be attractive candidates as delivery biosystems in tumor therapy.

Highly Loaded, Sustained-Release Microparticles of Curcumin for Chemoprevention

Curcumin, a dietary polyphenol, has preventive and therapeutic potential against several diseases. Because of the chronic nature of many of these diseases, sustained-release dosage forms of curcumin could be of significant clinical value. However, extreme lipophilicity and instability of curcumin are significant challenges in its formulation development. The objectives of this study were to fabricate an injectable microparticle formulation that can sustain curcumin release over a 1-month period and to determine its chemopreventive activity in a mouse model. Microparticles were fabricated using poly(D, L-lactide-co-glycolide) polymer. Conventional emulsion solvent evaporation method of preparing microparticles resulted in crystallization of curcumin outside of microparticles and poor entrapment (∼1%, w/w loading). Rapid solvent removal using vacuum dramatically increased drug entrapment (∼38%, w/w loading; 76% encapsulation efficiency). Microparticles sustained curcumin release over 4 weeks in vitro, and drug release rate could be modulated by varying the polymer molecular weight and/or composition. A single subcutaneous dose of microparticles sustained curcumin liver concentration for nearly a month in mice. Hepatic glutathione-s-transferase and cyclooxygenase-2 activities, biomarkers for chemoprevention, were altered following treatment with curcumin microparticles. The results of these studies suggest that sustained-release microparticles of curcumin could be a novel and effective approach for cancer chemoprevention.

Development of Petroleum-Based Carbon Composite Materials Containing Graphite/silicon Particles and Their Application to Lithium Ion Battery Anodes

ABSTRACT: Herein, a novel preparation method of highly homogeneous carbon-silicon composite materials waspresented. In contrast to conventional solvent evaporation method, a milled silicon-graphite or itsoxidized material were directly reacted with petroleum-derived pitch precursor. After thermal reactionunder high pressure, pitch-graphite-silicon composite was prepared. Carbon-graphite-silicon compositewere prepared by an air-oxidization and following carbonization. From energy dispersive spectroscopy,it was observed that small Si particles were highly embedded within carbon, which was confirmedby disappearance of Si peaks in Raman spectra. Furthermore, X-ray diffraction and Raman spectrarevealed that carbon crystallinity decreased when the strongly oxidized silicon-graphite was added,which was probably due to oxygen-induced cross-linking. From the anode application in lithiumion batteries, carbon-graphite-silicon composite anode displayed a high capacity (565 mAh g − 1 ), agood initial efficiency (68%) and an good cyclability (88% retention at 50 cycles), which wereattributed to the high dispersion of Si particles within cabon. In case of the strongly oxidized silicon-graphite addtion, a decrease of reversible capacity was observed due to its low crystallinity.Keywords : Pitch-graphite-Si composite, Petroleum pitch, Anode in lithium ion batteries

Spray-drying enteric polymers from aqueous solutions: A novel, economic, and environmentally friendly approach to produce pH-responsive microparticles

We describe a novel method to fabricate pH-responsive microparticles suitable for oral delivery using an aqueous-based spray-drying approach. The approach involves the neutralization and generation of water-soluble salt forms of enteric polymers. The methacrylic acid polymers (Eudragit L and Eudragit S) were added separately to aqueous solutions of ammonium hydrogen carbonate; the solutions were then spray-dried. FTIR analysis of the harvested microparticle products identified the presence of ammonium methacrylate with the appearance of a peak at 1550 cm −1 corresponding to the stretching of the N–H bond. Incubating the microparticles for three hours at 70 °C and 130 °C for the Eudragit S and L products, respectively, was sufficient to eradicate the ammonium residues. The microparticles, loaded with the model drug prednisolone, were spherical and small in size (2–5 μm). Moreover, the particles were gastro-resistant, and release was rapid and complete at small intestinal conditions. The pH threshold of release of the Eudragit S and Eudragit L microparticles was lowered from 7 and 6 to 6.5 and 5.5, respectively. In bicarbonate media, which are physiological and representative of the conditions of the proximal small intestine (mHanks) and the distal small intestine (Kreb’s), drug release from these spray-dried microparticles was faster compared to microparticles produced from conventional emulsion solvent evaporation methods. This new microparticle preparation concept obviates the need for organic solvents and utilizes spray-drying techniques that are amenable to industrial application; the approach therefore offers economic, safety, and environmental benefits.

Comparison of Spray Freeze Drying and the Solvent Evaporation Method for Preparing Solid Dispersions of Baicalein with Pluronic F68 to Improve Dissolution and Oral Bioavailability

The objective of this study was to prepare solid dispersions consisting of baicalein and a carrier with a low glass transition/melting point (Pluronic F68) by spray freeze drying (SFD). We compared these powders to those produced from the conventional solvent evaporation method. In the SFD process, a feeding solution was atomized above the surface of liquid nitrogen following lyophilization, which resulted in instantaneously frozen microparticles. However, solid dispersions prepared by the solvent evaporation method formed a sticky layer on the glass flask with crystalline baicalein separated out from the carrier. The powder samples were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), surface area measurement, differential scanning calorimetry, and Fourier transform infrared spectrometry. SEM and PXRD results suggested that the majority of baicalein in the SFD-processed solid dispersion was in the amorphous state, which has a higher specific surface area than pure baicalein. However, the majority of baicalein was recrystallized in the solid dispersion at the same composition prepared by the solvent evaporation method, which showed a similar dissolution rate to the physical mixture. SFD product was physically and chemically stable after being stored at 40 °C with low humidity for 6 months. After enzyme hydrolysis, baicalein in the SFD product displayed a significantly shorter T (max) and higher C (max) than pure baicalein after oral dosing. The relative bioavailability of the SFD product versus pure baicalein determined by comparing the AUC(0-12) was 233%, which demonstrated the significantly improved oral bioavailability of baicalein produced by the SFD technique.