CO Evaporation Research Articles

Ent-kaurenoic acid-enriched Mikania glomerata leaves-complexed β-cyclodextrin: Pharmaceutical development and in vivo antitumor activity in a sarcoma 180 mouse model

The extract obtained from Mikania glomerata leaves rich in ent-kaurenoic acid (ERKA) shows cytotoxic activity in vitro, but its hydrophobic nature and thermosensitivity are issues to be solved prior to in vivo antitumor studies. The purpose of this study was to investigate the antitumor activity of inclusion complexes formed between ERKA and β-cyclodextrin (ERKA:β-CD) in rodents. ERKA:β-CD complexes obtained by malaxation (MX) and co-evaporation (CE) methods were firstly characterized regarding their physical properties, encapsulation efficiency, and cytotoxicity againts L929 cells. The antitumor activity study was then performed in mice with sarcoma 180 treated with saline, 5-fluouracil (5FU) and ERKA:β-CD at 30, 100 and 300 µg/kg. The weight, volume, percentage of inhibition growth, gross and pathological features and positivity for TUNEL, ki67, NFκB and NRF2 in the tumors were assessed. Serum lactate-dehydrogenase activity (LDH), white blood cells count (WBC) and both gross and pathological features of the liver, kidneys and spleen were also evaluated. The formation of the inclusion complexes was confirmed by thermal analysis and FTIR, and they were non-toxic for L929 cells. The MX provided a better complexation efficiency. ERKA:β-CD300 promoted significant tumor growth inhibition, and attenuated the tumor mitotic activity and necrosis content, comparable to 5-fluorouracil. ERKA:β-CD300 also increased TUNEL-detected cell death, reduced Ki67 and NF-kB immunoexpression, and partially inhibited the serum LDH activity. No side effect was observed in ERKA:β-CD300-treated animals. The ERKA:β-CD inclusion complexes at 300 µg/kg displays antitumour activity in mice with low systemic toxicity, likely due to inhibition on the NF-kB signaling pathway and LDH activity.

Formulation and Development of Nanostructured Lipid Carriers for a Poorly Water-Soluble Drug: Furosemide

Aim: Formulation, development and evaluation of solid lipid nanoparticles. Background: It was found that furosemide (FU) was a very potent drug but it fails to produce bioavailability due to its BCS class IV, so drug- cyclodextrin (CD)- nanostructured lipid carriers (NLC) will be an alternative to improve solubility and permeability as a result of this overall bioavaibility will be improved. Objective: To improve the solubility of drug by using complexation of cyclodextrin. Coating with the lipids (NLC) will improve the permeability of the drug. Methods: To generate solid Furosemide–cyclodextrin complexes (FU–CD), two distinct CDs and three different techniques were used. The co-evaporation (COE) Furosemide-β-cyclodextrinloaded NLC (FU– β-CD-COE-loaded NLC) was obtained by emulsification ultrasonic dispersion method. The selected batch was suitably characterized for particle size, polydispersity index, zeta potential, Entrapment efficiency, Drug release study, and permeability study. The crystallization of the drug in the furosemide cyclodextrin complex (FU–CD complex) and the co-evaporation Furosemide- β-cyclodextrin-loaded NLC (FU–β-CD-COE-loaded NLC) was investigated by differential scanning calorimetry (DSC). The in vitro release study was carried out. Results: The FU–β-CD-COE-loaded NLC and FU–HP-β-CD-COE-loaded NLC (Hydroxypropyl) presented a superior physicochemical property and were selected for further study. The in vitro release study of the above selected batches exhibited a higher dissolution rate in the pH 5.8 phosphate buffer than Furosemide suspension and FU–NLC. The permeability studies of abovementioned batches were compared with FU-Suspension. Conclusion: The novel formulation considerably enhanced the solubility and permeability of furosemide for oral delivery, and was successfully developed.

Solubility enhancement of mefenamic acid by inclusion complex with β-cyclodextrin: in silico modelling, formulation, characterisation, and in vitro studies

The aim of this study was to prepare and characterise inclusion complexes of a low water-soluble drug, mefenamic acid (MA), with β-cyclodextrin (β-CD). First, the phase solubility diagram of MA in β-CD was drawn from 0 to 21 × 10−3 M of β-CD concentration. A job’s plot experiment was used to determine the stoichiometry of the MA:β-CD complex (2:1). The stability of this complex was confirmed by molecular modelling simulation. Three methods, namely solvent co-evaporation (CE), kneading (KN), and physical mixture (PM), were used to prepare the (2:1) MA:β-CD complexes. All complexes were fully characterised. The drug dissolution tests were established in simulated liquid gastric and the MA water solubility at pH 1.2 from complexes was significantly improved. The mechanism of MA released from the β-CD complexes was illustrated through a mathematical treatment. Finally, two in vitro experiments confirmed the interest to use a (2:1) MA:β-CD complex.

β-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity.

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in β-cyclodextrin (β-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:β-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:β-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:β-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:β-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.

Gas phase Elemental abundances in Molecular cloudS (GEMS): I. The prototypical dark cloud TMC 1.

GEMS is an IRAM 30m Large Program whose aim is determining the elemental depletions and the ionization fraction in a set of prototypical star-forming regions. This paper presents the first results from the prototypical dark cloud TMC 1. Extensive millimeter observations have been carried out with the IRAM 30m telescope (3 mm and 2 mm) and the 40m Yebes telescope (1.3 cm and 7 mm) to determine the fractional abundances of CO, HCO+, HCN, CS, SO, HCS+, and N2H+ in three cuts which intersect the dense filament at the well-known positions TMC 1-CP, TMC 1-NH3, and TMC 1-C, covering a visual extinction range from A V ~ 3 to ~20 mag. Two phases with differentiated chemistry can be distinguished: i) the translucent envelope with molecular hydrogen densities of 1-5×103 cm-3; and ii) the dense phase, located at A V > 10 mag, with molecular hydrogen densities >104 cm-3. Observations and modeling show that the gas phase abundances of C and O progressively decrease along the C+/C/CO transition zone (A V ~ 3 mag) where C/H ~ 8×10-5 and C/O~0.8-1, until the beginning of the dense phase at A V ~ 10 mag. This is consistent with the grain temperatures being below the CO evaporation temperature in this region. In the case of sulfur, a strong depletion should occur before the translucent phase where we estimate a S/H ~ (0.4 - 2.2) ×10-6, an abundance ~7-40 times lower than the solar value. A second strong depletion must be present during the formation of the thick icy mantles to achieve the values of S/H measured in the dense cold cores (S/H ~8×10-8). Based on our chemical modeling, we constrain the value of ζ H2 to ~ (0.5 - 1.8) ×10-16 s-1 in the translucent cloud.

Drug-in-cyclodextrin-in-liposomes: A novel drug delivery system for flurbiprofen

A novel delivery system based on drug-cyclodextrin (CD) complexation and liposomes has been developed to improve therapeutic effect. Three different means, i.e., co-evaporation (COE), co-ground (GR) and co-lyophilization (COL) and three different CDs (β-CD, HP-β-CD and SBE-β-CD) were contrasted to investigate the characteristics of the end products. FP/FP-CD loaded liposomes were obtained by thin layer evaporation technique. Size, zeta potential and encapsulation efficiency were investigated by light scattering analysis and minicolumn centrifugation. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) showed the amorphous form of complexes and spherical morphology of FP-HP-β-CD COE loaded liposomes. The pH 7.4 phosphate buffer solution (PBS) was selected as the medium for the in vitro release. Wistar rats were put into use to study the pharmacokinetic behavior in vivo. FP-HP-β-CD COE loaded liposomes showed the better physicochemical characters that followed the average particle size, polydispersity index, zeta potential and mean encapsulation efficiency 158±10nm, 0.19±0.1, −12.4±0.1mW and 56.1±0.5%, separately. The relative bioavailability of FP-HP-β-CD COE loaded liposomes was 420%, 201% and 402% compared with FP solution, FP-HP-β-CD and FP-liposomes, respectively. In conclusion, the novel delivery system improved the relative bioavailability of FP significantly and provided a perspective way for delivery of insoluble drugs.

Inclusion complexes of bendamustine with β-CD, HP-β-CD and Epi-β-CD: in-vitro and in-vivo evaluation

The objective of the present work was to investigate the inclusion behavior of bendamustine (BM) with β-cyclodextrin and its hydrophilic derivatives (HP-β-CD and Epi-β-CD) for the enhancement of aqueous solubility, dissolution and bioavailability. The supramolecular binary complexes were prepared by three different methods, viz. physical mixture (PM), kneading (KND) and co-evaporation (COE). Phase-solubility study revealed the higher solubilizing and complexing ability of polymerized cyclodextrin (Ks = 645 M−1) than parent cyclodextrin (Ks = 43 M−1) and chemically derived cyclodextrin (Ks = 100 M−1). Meanwhile, the solubility of BM was significantly enhanced in phosphate buffer of pH 6.8, which was 24.5 folds greater compared with the phosphate buffer pH 4.5 and four times greater than aqueous medium. The dissolution efficiency was found to be highest for BM: Epi-β-CD complex (87%) compared to BM: HP-β-CD complex (84%), BM: β-CD (79%) and pure drug (20%). In-vivo pharmacokinetic study revealed that the bioavailability of BM was enhanced 2.55 times on complexation with Epi-β-CD using KND method. The t1/2 of BM was increased from 34.2 min to approximately 75.7 min, allowing the absorption for longer time. The order of increase in solubility, dissolution and bioavailability of BM was KND > COE > PM > pure drug. Thus, the strategy of host–guest inclusion was very effective and could be successfully used in the development of suitable pharmaceutical dosage form with enhanced therapeutic activity.

Chemical variation in molecular cloud cores in the Orion A cloud. II.

Abstract We have mapped six molecular cloud cores in the Orion A giant molecular cloud (GMC), whose kinetic temperatures range from 10 to 30 K, in CCS and N2H+ with the Nobeyama 45 m radio telescope to study their chemical characteristics. We identified 31 intensity peaks in the CCS and N2H+ emission in these molecular cloud cores. We found, for cores with temperatures lower than ∼ 25 K, that the column density ratio of N(N2H+)/N(CCS) is low toward starless core regions while it is high toward star-forming core regions, in cases where we detected both the CCS and N2H+ emission. This is very similar to the tendency found in dark clouds (kinetic temperature ∼ 10 K). The criterion found in the Orion A GMC is N(N2H+)/N(CCS) ∼ 2–3. In some cases, both CCS and N2H+ emission is detected toward protostars. A secondary late-stage CCS peak in the chemical evolution caused by CO depletion may be a possible explanation for this. We found that the chemical variation of CCS and N2H+ can also be used as a tracer of evolution in warm (10–25 K) GMC cores. On the other hand, some protostars do not accompany N2H+ intensity peaks but are associated with dust continuum emitting regions, suggesting that the N2H+ abundance might be decreased due to CO evaporation in warmer star-forming sites.

Investigating the inclusion of the Ag(I)-nimesulide complex into β-cyclodextrin: studies in solution and in the solid state

The present work describes the preparation and characterization of inclusion systems involving β-CD and the silver(I) nimesulide coordination complex (Ag-NMS), prepared by kneading (K) and co-evaporation (CE) methods. Solid state characterization by DSC, XRD and IR vibrational spectroscopic measurements provided remarkable evidences of the formation of true inclusion systems. Solution measurements provided information about the inclusion mode. The UV–Vis spectroscopy was used to obtain the association constants by the Scatchard method, and the value obtained was 370 ± 2 L mol−1. The 1H NMR spectroscopic measurements indicate a total inclusion of the guest into the cavity. A 2D NOESY experiment was carried out for the inclusion complex. The spectrum shows that hydrogens 3–6 of the cyclodextrin clearly correlate with the protons of the phenoxy ring of nimesulide in the Ag-NMS coordination compound, which confirms the formation of the inclusion complex. The antibacterial activities of the Ag-NMS and CE-[(Ag-NMS)·β-CD] inclusion system were evaluated by the well diffusion method over Escherichia coli and Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) pathogenic bacterial strains. The observed data shows the significant antibacterial activity of the Ag-NMS coordination complex, and no activity for the inclusion complex under the same considered conditions.

Production of high quality clarified pomegranate juice concentrate by membrane processes

The potential of osmotic distillation (OD) and coupled operation of membrane distillation (MD) and OD processes (CO) for concentration of pomegranate juice was investigated comparatively with a view to the impact on product quality and process performance. The pomegranate juice (17° Bx) which was previously clarified by combined application of fining agents (gelatin and bentonite) and ultrafiltration (UF), was concentrated up to 55–57° Bx by OD, CO or thermal evaporation (TE). Both membrane-based concentration techniques were very efficient in preventing the original characteristics (pH, total titratable acidity (TTA), color characteristics, total antioxidant activity (TAA), total phenolic content (TPC), total monomeric anthocyanins (TMA), individual phenolics and organic acid composition) of the clarified juice. Concentration with TE, however, resulted considerable losses in natural color and TAA, and in a marked formation of hydroxymethyl furfural (HMF). CO was the most feasible approach for concentration of pomegranate juice, allowing to reach higher concentration levels in shorter periods of operation time with a slight increase (5°C) in temperature of the juice in comparison with OD. The results of this study highlighted the need for an effective pre-clarification step prior to UF to contribute to the improvement of the efficiency of the overall membrane-based system.

RESOLVED DEPLETION ZONES AND SPATIAL DIFFERENTIATION OF N2H+AND N2D+

We present a study on the spatial distribution of N2D+ and N2H+ in thirteen protostellar systems. Eight of thirteen objects observed with the IRAM 30m telescope show relative offsets between the peak N2D+ (J=2-1) and N2H+ (J=1-0) emission. We highlight the case of L1157 using interferometric observations from the Submillimeter Array and Plateau de Bure Interferometer of the N2D+ (J=3-2) and N2H+ (J=1-0) transitions respectively. Depletion of N2D+ in L1157 is clearly observed inside a radius of ~2000 AU (7") and the N2H+ emission is resolved into two peaks at radii of ~1000 AU (3.5"), inside the depletion region of N2D+. Chemical models predict a depletion zone in N2H+ and N2D+ due to destruction of H2D+ at T ~ 20 K and the evaporation of CO off dust grains at the same temperature. However, the abundance offsets of 1000 AU between the two species are not reproduced by chemical models, including a model that follows the infall of the protostellar envelope. The average abundance ratios of N2D+ to N2H+ have been shown to decrease as protostars evolve by Emprechtinger et al., but this is the first time depletion zones of N2D+ have been spatially resolved. We suggest that the difference in depletion zone radii for N2H+ and N2D+ is caused by either the CO evaporation temperature being above 20 K or an H2 ortho-to-para ratio gradient in the inner envelope.

The abundance of C18O and HDO in the envelope and hot core of the intermediate mass protostar NGC 7129 FIRS 2

NGC 7129 FIRS 2 is a young intermediate-mass (IM) protostar, which is associated with two energetic bipolar outflows and displays clear signs of the presence of a hot core. It has been extensively observed with ground based telescopes and within the WISH Guaranteed Time Herschel Key Program. We present new observations of the C18O 3-2 and the HDO 3_{12}-2_{21} lines towards NGC 7129 FIRS 2. Combining these observations with Herschel data and modeling their emissions, we constrain the C18O and HDO abundance profiles across the protostellar envelope. In particular, we derive the abundance of C18O and HDO in the hot core. The intensities of the C18O lines are well reproduced assuming that the C18O abundance decreases through the protostellar envelope from the outer edge towards the centre until the point where the gas and dust reach the CO evaporation temperature (~20-25 K) where the C18O is released back to the gas phase. Once the C18O is released to the gas phase, the modelled C18O abundance is found to be ~1.6x10^{-8}, which is a factor of 10 lower than the reference abundance. This result is supported by the non-detection of C18O 9-8, which proves that even in the hot core (T_k>100 K) the CO abundance must be 10 times lower than the reference value. Several scenarios are discussed to explain this C18O deficiency. One possible explanation is that during the pre-stellar and protostellar phase, the CO is removed from the grain mantles by reactions to form more complex molecules. Our HDO modeling shows that the emission of HDO 3_{12}-2_{21} line is maser and comes from the hot core (T_k>100 K). Assuming the physical structure derived by Crimier et al. (2010), we determine a HDO abundance of ~0.4 - 1x10^{-7} in the hot core of this IM protostar, similar to that found in the hot corinos NGC 1333 IRAS 2A and IRAS 16293-2422.

Thermodynamic and Physical Interactions between Novel Polymeric Surfactants and Lipids: Toward Designing Stable Polymer–Lipid Complexes

Surfactant amphiphilic macromolecules (AMs) were complexed with a 1:1 ratio of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), either by a coevaporation (CE) or postaddition (PA) method, to form AM-lipid complexes with enhanced drug delivery applications. By characterizing the surfactant-lipid interactions, these heterogeneous drug delivery systems can be better controlled and engineered for optimal therapeutic outcomes. In this study, the physical interactions between DOPE:DOTAP liposomes and AM surfactants were investigated. Langmuir film balance and isothermal calorimetry studies showed cooperative intermolecular interactions between pure lipids and AM in monolayers and high thermostability of structure formed by the addition of AM micelles to DOTAP:DOPE vesicles in buffer solution respectively. Increasing the AM weight ratio in the complexes via the CE method led to complete vesicle solubilization--from lamellar aggregates, to a mixture of coexisting vesicles and micelles, to mixed micelles. Isothermal calorimetry evaluation of AM-lipid complexes shows that, at higher AM weight ratios, PA-produced complexes exhibit greater stability than complexes at lower AM weight ratios. Similar studies show that AM-lipid complexes produced by the CE methods display stronger interactions between AM-lipid components than complexes produced by the PA method. The results suggest that the PA method produces vesicles with AM molecules associated with its outer leaflet only (i.e., an AM-coated vesicle), while the CE method produces complexes ranging from mixed vesicles to mixed micelle in which the AM-lipid components are more intimately associated. These results will be helpful in the design of AM-lipid complexes as structurally defined, stable, and effective drug delivery systems.

A comparative study of complexation methods for cefdinir-hydroxypropyl-β-cyclodextrin system

The aim of this study was to investigate the effect of hydroxypropyl-β-cyclodextrin (HPβCD) on the solubility and dissolution rate of Cefdinir (CEF). The methods that were employed to prepare CEF–HPβCD complexes were Kneading (KN), Co-evaporation (CE), Spray drying (SD) and a novel approach of Microwave irradiation (MWI). The formation of inclusion complexes with HPβCD in the solid state, were characterized by Differential Scanning Calorimetry (DSC), Fourier Transformation Infrared spectroscopy (FTIR), Proton Nuclear Magnetic Resonance Spectroscopy (NMR), X Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) studies, and comparative studies on the in vitro dissolution of CEF were carried out. Phase solubility profile with HPβCD was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complexes. Characterization of binary systems by DSC, FTIR, NMR, XRD and SEM indicated that SD and MWI method resulted in formation of true complexes. Binary systems showed significant increase in dissolution rate as compared to plain drug. Amongst the various binary systems, MWI products were prepared in least time with better yield and highest dissolution rate.

Effect of preparation method on complexation of Cefdinir with β-cyclodextrin

The inclusion behaviour of β-cyclodextrin (βCD) was studied toward Cefdinir (CEF) in order to enhance the solubility and dissolution rate, following cyclodextrin complexation. Drug cyclodextrin solid systems were prepared by conventional methods of kneading (KN), co-evaporation (CE), spray drying (SD) and with a novel approach of microwave irradiation (MWI). The formation of inclusion complexes with βCD in the solid state, were confirmed by Differential scanning calorimetry (DSC), Fourier Transform Infrared spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) studies, and comparative studies on the in vitro dissolution of CEF were carried out. Characterization of binary system by DSC, FTIR and SEM indicated that SD and MWI method resulted in formation of true complexes. Binary systems showed significant increase in dissolution rate as compared to plain drug. Amongst the binary systems MWI products were prepared in least time with better yield and highest dissolution rate.

Corona-like atmospheric escape from KBOs: II. The behavior of aerosols

In Levi and Podolak (Levi, A., Podolak, M. [in press] Icarus) we applied the theory of coronal expansion to gas escape from a small, cold, object such as those found in the Kuiper belt. Here we extend the theory to include aerosols that are lifted off the surface by the escaping gas. Aerosols carried by the gas but still gravitationally bound, tend to be lifted to a height above the surface that is dependent on the aerosol radius, so that in steady state the variation of aerosol radius with height is well-defined. We develop an extension of Parker’s coronal flow theory to include the effect of aerosols carried along by the gas and use this to estimate the optical depth of such an atmosphere. For KBOs with CO evaporation from the surface and with radii in the range 245–334 km, line-of-site optical depths through the atmosphere can exceed one at heights of a few hundred kilometers above the surface. Such aerosol layers should be observable, and might be used to infer the flow proprieties of the escaping gas.

Preparation and Solid-State Characterization of Inclusion Complexes Formed Between Miconazole and Methyl-β-Cyclodextrin

The aim of this study is to confirm the formation of inclusion complexes between miconazole (MCZ) and two derivatives of beta-cyclodextrin, methyl-beta-cyclodextrin (MbetaCD) and 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) in aqueous solution by phase solubility studies. Inclusion complexes with MbetaCD in the solid state were then prepared by different methods, i.e., kneading, coevaporation (COE), spray-drying (SD), and lyophilization (LPh). The physicochemical properties of these complexes were subsequently studied by means of differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction techniques. Phase solubility diagrams with MbetaCD and HPbetaCD were classified as A(P) type, indicating the formation of 1:1 and 1:2 stoichiometric inclusion complexes. The apparent stability constants (K(S)) calculated from the phase solubility diagram were 145.69 M(-1) (K(1:1)) and 11.11 M(-1) (K(1:2)) for MbetaCD and 126.94 M(-1) (K(1:1)) and 2.20 M(-1) (K(1:2)) for HPbetaCD. The method of preparation of the inclusion complexes in the solid state was shown to greatly affect the properties of the formed complex. Hence, the LPh, SD, and COE methods produce true inclusion complexes between MCZ and MbetaCD. In contrast, crystalline drug was still clearly detectable in the kneaded (KN) product.

Supercritical Antisolvent Versus Coevaporation— Preparation and Characterization of Solid Dispersions

The objective of this work was to improve the dissolution rate and aqueous solubility of oxeglitazar. Solid dispersions of oxeglitazar in PVP K17 (polyvinilpyrrolidone) and poloxamer 407 (polyoxyethylene-polyoxypropylene block copolymer) were prepared by supercritical antisolvent (SAS) and coevaporation (CoE) methods. Drug-carrier formulations were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography, UV/VIS spectroscopy and in vitro dissolution tests. The highest dissolution rate (nearly 3-fold higher than raw drug) was achieved by preparation of drug/PVP K17 coevaporate. Oxeglitazar/PVP K17 solid dispersions were stabilized by hydrogen bonding but contained higher amount of residual dichloromethane (DCM) than poloxamer 407 formulations regardless of the method of preparation. SAS prepared oxeglitazar/poloxamer 407 dissolved more than two times faster than raw drug. However, unlike PVP K17, poloxamer 407 did not form a single phase amorphous solid solution with oxeglitazar which has been manifested in higher degrees of crystallinity, too. Among the two techniques, evaluated in this work, conventional coevaporation resulted in higher amorphous content but SAS reduced residual solvent content more efficiently.

Evaluation of supercritical fluid technology as preparative technique of benzocaine–cyclodextrin complexes—Comparison with conventional methods

The objective of this study was to investigate the effect of the preparation method on the physico-chemical properties of complexes prepared between β-cyclodextrin (β-Cyd) and benzocaine (BZC). In particular, the effectiveness of a new technique based on supercritical carbon dioxide (SC CO 2) for preparing solid drug–cyclodextrin complexes was investigated and compared to other more conventional methods such as kneading (KN), co-evaporation (COE), co-grinding (GR) and sealed-heating (S.H.). Effects of temperature, pressure and exposure time on the properties of complexes prepared by SC CO 2 technology were also studied. The different systems were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD) and dissolution test according to the dispersed amount method. The co-grinding (GR) method resulted in amorphous products while other methods led to crystalline or partially amorphous products depending on both the method and its experimental conditions. SC CO 2 method revealed to be an effective technique for preparing solid systems between β-cyclodextrin and benzocaine, avoiding the use of organic solvents (and problems of their complete removal) and allowing an easy scale-up of the process. As for the influence of the experimental conditions in promoting the solid-state drug–carrier interaction when using the SC CO 2 method, temperature seemed to play the major role, whereas pressure and exposure times had more limited effects. Dissolution tests confirmed a limited but favourable effect in increasing the exposure time, while indicated a possible interaction effect between temperature and pressure in influencing the dissolution performance of the final product. The best product obtained by the SC CO 2 method showed dissolution properties similar to those of the co-ground product and only slightly lower than the system obtained by sealed-heating, which was the most effective technique.

Solid Dispersions of Oxeglitazar in PVP K17 and Poloxamer 407 by Supercritical Antisolvent and Coevaporation Methods

The objective of this work was to improve the dissolution rate and aqueous solubility of oxeglitazar. Solid dispersions of oxeglitazar in PVP K17 (polyvinilpyrrolidone) and Poloxamer 407 (polyoxyethylene-polyoxypropylene block copolymer) were prepared by supercritical antisolvent (SAS) and coevaporation (CoE) methods. Drug-carrier formulations were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography, UV/VIS spectroscopy and in vitro dissolution tests. The highest dissolution rate (nearly 3-fold higher than raw drug) was achieved by preparation of drug/PVP K17 coevaporate. Oxeglitazar/PVP K17 solid dispersions were stabilized by hydrogen bonding but contained higher amount of residual DCM than Poloxamer 407 formulations regardless of the method of preparation. SAS prepared oxeglitazar/Poloxamer 407 dissolved more than two times faster than raw drug. However, unlike PVP K17, Poloxamer 407 did not form a single phase amorphous solid solution with oxeglitazar which has been manifested in higher degrees of crystallinity, too. Among the two techniques, evaluated in this work, conventional coevaporation resulted in higher amorphous content but SAS reduced residual solvent content more efficiently.