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1.
Mol Pharm ; 19(2): 532-546, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34958588

RESUMO

The present study systematically investigates the effect of annealing conditions and the Kolliphor P 407 content on the physicochemical and structural properties of Compritol (glyceryl behenate) and ternary systems prepared via melt cooling (Kolliphor P 407, Compritol, and a hydrophilic API) representing solid-lipid formulations. The physical properties of Compritol and the ternary systems with varying ratios of Compritol and Kolliphor P 407 were characterized using differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SWAXS) and infrared (IR) spectroscopy, and hot-stage microscopy (HSM), before and after annealing. The change in the chemical profiles of different Compritol components as a function of annealing was evaluated using 1H NMR spectroscopy. While no change in the polymorphic form of API and Kolliphor P 407 occurred during annealing, a systematic conversion of the α- to ß-form was observed in the case of Compritol. Furthermore, the polymorphic transformation of Compritol was found to be dependent on the Kolliphor P 407 content. As per the Flory-Huggins mixing theory, higher miscibility was observed in the case of monobehenin-Kolliphor P 407, monobehenin-dibehenin, and dibehenin-tribehenin binary mixtures. The miscibility of Kolliphor P 407 with monobehenin and 1,2-dibehenin was confirmed by 1H NMR analysis. The observed higher miscibility of Kolliphor P 407 with monobehenin and 1,2-dibehenin is proposed as the trigger for the physical separation from the 1,3-diglyceride and triglycerides during melt solidification of the formulations. The phase separation is postulated as the mechanism underlying the formation of a stable ß-polymorphic form (a native form of 1,3-diglyceride) of Compritol upon annealing. This finding is expected to have an important implication for developing stable solid-lipid-surfactant-based drug formulations.


Assuntos
Excipientes , Tensoativos , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Excipientes/química , Transição de Fase , Solubilidade , Tensoativos/química
2.
Molecules ; 27(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36080368

RESUMO

Disulfiram (DS), known as an anti-alcoholism drug, has shown a potent antiviral activity. Still, the potential clinical application of DS is limited by its low water solubility and rapid metabolism. Cyclodextrins (CDs) have been widely used to improve the solubility of drugs in water. In this study, five concentrations of hydroxypropyl ß-cyclodextrin (HP) and sulfobutyl ether ß-cyclodextrin (SBE) were used to form inclusion complexes of DS for enhanced solubility. Solutions were freeze-dried, and the interaction between DS and CD was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the nebulization properties of the DS-CD solutions were studied. The aqueous solubility of DS increased significantly when loaded to either of both CDs. The phase solubility of both complexes was a linear function of the CD concentration (AL type). Furthermore, physicochemical characterization studies showed a potent inclusion of the drug in the CD-DS complexes. Aerosolization studies demonstrated that these formulations are suitable for inhalation. Overall, the CD inclusion complexes have great potential for the enhancement of DS solubility. However, further studies are needed to assess the efficacy of DS-CD inclusion complexes against SARS-CoV-2 via nebulization.


Assuntos
COVID-19 , Ciclodextrinas , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina/química , COVID-19/tratamento farmacológico , Varredura Diferencial de Calorimetria , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Dissulfiram/farmacologia , Humanos , SARS-CoV-2 , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Água , Difração de Raios X , beta-Ciclodextrinas/química
3.
Molecules ; 27(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36080433

RESUMO

Non-isothermal differential scanning calorimetry (DSC) was used to study the influences of particle size (daver) and heating rate (q+) on the structural relaxation, crystal growth and decomposition kinetics of amorphous indomethacin. The structural relaxation and decomposition processes exhibited daver-independent kinetics, with the q+ dependences based on the apparent activation energies of 342 and 106 kJ·mol-1, respectively. The DSC-measured crystal growth kinetics played a dominant role in the nucleation throughout the total macroscopic amorphous-to-crystalline transformation: the change from the zero-order to the autocatalytic mechanism with increasing q+, the significant alteration of kinetics, with the storage below the glass transition temperature, and the accelerated crystallization due to mechanically induced defects. Whereas slow q+ led to the formation of the thermodynamically stable γ polymorph, fast q+ produced a significant amount of the metastable α polymorph. Mutual correlations between the macroscopic and microscopic crystal growth processes, and between the viscous flow and structural relaxation motions, were discussed based on the values of the corresponding activation energies. Notably, this approach helped us to distinguish between particular crystal growth modes in the case of the powdered indomethacin materials. Ediger's decoupling parameter was used to quantify the relationship between the viscosity and crystal growth. The link between the cooperativity of structural domains, parameters of the Tool-Narayanaswamy-Moynihan relaxation model and microscopic crystal growth was proposed.


Assuntos
Indometacina , Varredura Diferencial de Calorimetria , Cristalização , Indometacina/química , Temperatura , Temperatura de Transição , Viscosidade
4.
Int J Mol Sci ; 23(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36077212

RESUMO

In this paper, we thoroughly investigated the physical stability of the anti-inflammatory drug etoricoxib, which has been reported earlier to be resistant to recrystallization in its glassy and supercooled states at ambient pressure. Our unique application of the standard refractometry technique showed that the supercooled liquid of the drug was able to recrystallize during isothermal experiments in atmospheric conditions. This enabled us to determine the crystallization onset timescale and nucleation energy barrier of etoricoxib for the first time. As the physical instability of etoricoxib requires working out an efficient method for improving the drug's resistance to recrystallization to maintain its amorphous form utility in potential pharmaceutical applications, we focused on finding a solution to this problem, and successfully achieved this purpose by preparing binary mixtures of etoricoxib with octaacetylmaltose. Our detailed thermal, refractometry, and molecular dynamics studies of the binary compositions near the glass transition revealed a peculiar behavior of the glass transition temperatures when changing the acetylated disaccharide concentration in the mixtures. Consequently, the anti-plasticization effect on the enhancement of physical stability could be excluded, and a key role for specific interactions in the improved resistance to recrystallization was expected. Invoking our previous results obtained for etoricoxib, the chemically similar drug celecoxib, and octaacetylmaltose, we formulated a hypothesis about the molecular mechanisms that may cause an impediment to crystal nuclei formation in the amorphous mixtures of etoricoxib with octaacetylmaltose. The most plausible scenario may rely on the formation of hydrogen-bonded heterodimers of the drug and excipient molecules, and the related drop in the population of the etoricoxib homodimers, which disables the nucleation. Nevertheless, this hypothesis requires further investigation. Additionally, we tested some widely discussed correlations between molecular mobility and crystallization properties, which turned out to be only partially satisfied for the examined mixtures. Our findings constitute not only a warning against manufacturing the amorphous form of pure etoricoxib, but also evidence for a promising outcome for the pharmaceutical application of the amorphous compositions with octaacetylmaltose.


Assuntos
Simulação de Dinâmica Molecular , Vitrificação , Varredura Diferencial de Calorimetria , Estabilidade de Medicamentos , Etoricoxib , Excipientes/química
5.
Food Res Int ; 160: 111650, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36076440

RESUMO

Chlorophyll-loaded nano/microparticles were fabricated using zein, casein, and whey protein isolate as carrier agents. Chlorophyll was adequately loaded in these wall materials with encapsulation efficiency, loading capacity, and particle size ranging from 83.6 to 96.3%, 0.8 to 5.5%, and 483 to 1020 nm respectively. As unveiled by differential scanning calorimetry (DSC), chlorophyll existed in a non-crystalline state inside the different wall materials. The encapsulation techniques and different carrier agents were effective in protecting chlorophyll from acid pH (pH 2 to 6, chlorophyll retention; 39.3 to 97.8%) and light (chlorophyll retention; 41.6 to 65.5%) conditions. Employing the first-order model to investigate the thermal degradation kinetics of the different chlorophyll loaded nano/microparticles showed activation energy, Gibbs free energy, enthalpy, and entropy change ranging from 49.6 to 70.1 kJ/mol, 93.4 to 100.0 kJ mol-1, 46.6 to 67.4 kJ mol-1, and -147.8 to -86.4 J mol-1 K-1, respectively.


Assuntos
Clorofila , Varredura Diferencial de Calorimetria , Clorofila/química , Entropia , Cinética , Termodinâmica
6.
Molecules ; 27(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36080157

RESUMO

Flavonoids are biologically active natural products of great interest for their potential applications in functional foods and pharmaceuticals. A hesperetin-7-O-glucoside inclusion complex with ß-cyclodextrin (HEPT7G/ßCD; SunActive® HCD) was formulated via the controlled enzymatic hydrolysis of hesperidin with naringinase enzyme. The conversion rate was nearly 98%, estimated using high-performance liquid chromatography analysis. The objective of this study was to investigate the stability, solubility, and spectroscopic features of the HEPT7G/ßCD inclusion complex using Fourier-transform infrared (FTIR), Raman, ultraviolet-visible absorption (UV-vis), 1H- and 13C- nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC-MS), scanning electron microscopy (SEM), and powdered X-ray diffraction (PXRD) spectroscopic techniques including zeta potential, Job's plot, and phase solubility measurements. The effects of complexation on the profiles of supramolecular interactions in analytic features, especially the chemical shifts of ß-CD protons in the presence of the HEPT7G moiety, were evaluated. The stoichiometric ratio, stability, and solubility constants (binding affinity) describe the extent of complexation of a soluble complex in 1:1 stoichiometry that exhibits a greater affinity and fits better into the ß-CD inner cavity. The NMR spectroscopy results identified two different configurations of the HEPT7G moiety and revealed that the HEPT7G/ßCD inclusion complex has both -2S and -2R stereoisomers of hesperetin-7-O-glucoside possibly in the -2S/-2R epimeric ratio of 1/1.43 (i.e., -2S: 41.1% and -2R: 58.9%). The study indicated that encapsulation of the HEPT7G moiety in ß-CD is complete inclusion, wherein both ends of HEPT7G are included in the ß-CD inner hydrophobic cavity. The results showed that the water solubility and thermal stability of HEPT7G were apparently increased in the inclusion complex with ß-CD. This could potentially lead to increased bioavailability of HEPT7G and enhanced health benefits of this flavonoid.


Assuntos
Hesperidina , beta-Ciclodextrinas , Varredura Diferencial de Calorimetria , Flavonoides/química , Glucosídeos , Prótons , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X , beta-Ciclodextrinas/química
7.
J Chem Phys ; 157(7): 071101, 2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-35987598

RESUMO

The kinetics of the first order liquid-liquid transition (LLT) in a single-component liquid D-mannitol have been examined in detail by the high rate of flash differential scanning calorimetry measurements. By controlling the annealing temperature, the phase X formation from the supercooled liquid is distinguished by either a nucleation-growth or a spinodal-decomposition type of LLT. In the measured time-temperature-transformation curve the portion covering the nucleation-growth type of LLT can be well fitted with a classical nucleation theory analysis.


Assuntos
Manitol , Varredura Diferencial de Calorimetria , Cinética , Manitol/química , Temperatura
8.
Biochim Biophys Acta Proteins Proteom ; 1870(9): 140830, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35934299

RESUMO

Differential scanning calorimetry (DSC) determines the enthalpy change upon protein unfolding and the melting temperature of the protein. Performing DSC of a protein in the presence of increasing concentrations of specifically-binding ligand yields a series of curves that can be fit to obtain the protein-ligand dissociation constant as done in the fluorescence-based thermal shift assay (FTSA, ThermoFluor, DSF). The enthalpy of unfolding, as directly determined by DSC, helps improving the precision of the fit. If the ligand binding is linked to protonation reactions, the intrinsic binding constant can be determined by performing the affinity determination at a series of pH values. Here, the intrinsic, pH-independent, affinity of acetazolamide binding to carbonic anhydrase (CA) II was determined. A series of high-affinity ligands binding to CAIX, an anticancer drug target, and CAII showed recognition and selectivity for the anticancer isozyme. Performing the DSC experiment in buffers of highly different enthalpies of protonation enabled to observe the ligand unbinding-linked protonation reactions and estimate the intrinsic enthalpy of binding. The heat capacity of combined unfolding and unbinding was determined by varying the ligand concentrations. Taken together, these parameters provided a detailed thermodynamic picture of the linked ligand binding and protein unfolding process.


Assuntos
Anidrase Carbônica II , Inibidores da Anidrase Carbônica , Varredura Diferencial de Calorimetria , Anidrase Carbônica II/química , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/metabolismo , Ligantes , Ligação Proteica
9.
Eur J Pharm Biopharm ; 178: 82-93, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35932965

RESUMO

Co-amorphous strategy has been extensively investigated to improve the dissolution of hydrophobic drugs. Here, epigallocatechin-3-gallate (EGCG) was exploited as a co-former in co-amorphous systems based on its unique structure including phenyl rings, phenolic hydroxyl groups and the galloyl moiety. Two model BCS class II drugs, simvastatin (SIM) and nifedipine (NIF), were selected to be co-amorphized with EGCG. All drug-EGCG systems at three molar ratios became amorphous by the means of spray drying and showed high physically stable either under dry condition and 75 % RH at 40 °C or under dry conditions at 25 °C. The optimal feed molar ratios of both EGCG based co-amorphous systems fabricated were determined to be three, under which the significant increases were obtained in the maximum apparent concentrations of 4.90-fold for SIM at 1 h and 106.03-fold for NIF at 0.25 h compared to crystalline drugs by non-sink dissolution studies. The underlying molecular mechanisms of two co-amorphous systems formation were involved in molecular miscibility, hydrogen bonds and π-π stacking interactions unraveled by means of DSC, FTIR and molecular dynamics simulations. More to the point, oral pharmacokinetic studies in rats demonstrated that co-amorphous SIM-EGCG and NIF-EGCG systems at 1:3 have a significant increase in Cmax of 1.81- and 5.69-fold, and AUC 0-24h of 1.62- and 4.57-fold compared with those of corresponding crystalline drugs, respectively. In conclusion, EGCG is proved to be a promising co-former in co-amorphous systems.


Assuntos
Nifedipino , Sinvastatina , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Catequina/análogos & derivados , Estabilidade de Medicamentos , Nifedipino/química , Ratos , Sinvastatina/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
10.
Int J Mol Sci ; 23(15)2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35955896

RESUMO

Early pregnancy loss (EPL) is a relatively common pathology of which almost 50% of cases remain idiopathic. In the search for novel biomarkers, differential scanning calorimetry (DSC) is intensively used to characterize the thermodynamic behavior of blood plasma/serum proteome in health and disease. Herein, for the first time, we investigate the DSC denaturation profiles of blood plasma derived from patients suffering EPL compared to healthy pregnant and non-pregnant women. Data analysis reveals that 58% of the EPL thermograms differ significantly from those of healthy pregnant women. Thermal stabilization of a fraction of albumin-assigned transition with concomitant suppression of the major and enhancement of the globulin-assigned transition are characteristic features of EPL calorimetric profiles that could be used as a new indicator of a risk pregnancy. The presented results suggest an altered composition or intermolecular interactions of the plasma proteome of women with EPL. In addition, the alterations of the EPL thermograms correlate with the increased blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and a higher prevalence of the polymorphism in the plasminogen activator inhibitor type-1 (PAI-1) gene, suggesting an expression of an overall enhanced immune response. The concomitant changes in plasma thermograms confirm the potential of the DSC approach for distinguishing changes in the pathological state of the blood plasma proteome.


Assuntos
Aborto Espontâneo , Proteoma , Varredura Diferencial de Calorimetria , Citocinas/genética , Feminino , Genótipo , Humanos , Plasma/química , Inibidor 1 de Ativador de Plasminogênio/genética , Gravidez , Proteoma/genética
11.
J Agric Food Chem ; 70(32): 9980-9989, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35921686

RESUMO

Thermal treatment applied during the cooking of pulses leads to denaturation and even aggregation of the proteins, which may impact protein digestibility. Thermal transitions of lentil, chickpea, and bean proteins were studied using differential scanning calorimetry (DSC). Protein-enriched samples were obtained by dry air classification of dehulled seeds and were heated to 160 °C, with water contents ranging from 0.2 to 4 kg/kg on a dry basis. The DSC peaks of the resulting endotherms were successfully modeled as overlapping Gaussian functions. The denaturation temperatures were modeled as a function of the temperature according to the Flory-Huggins theory. The modeling allows for the calculation of the degree of protein transition for any temperature and moisture condition. The denaturation diagrams reflect the different protein compositions of lentil, chickpea, and bean (particularly the 11S/7S globulin ratio). Chickpea proteins were more thermally stable than those from lentil and bean. Proteins underwent an irreversible transition, suggesting that unfolding and aggregation were coupled.


Assuntos
Cicer , Fabaceae , Lens (Planta) , Varredura Diferencial de Calorimetria , Fabaceae/química , Desnaturação Proteica , Água
12.
Int J Mol Sci ; 23(16)2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36012748

RESUMO

The purpose of this study was to investigate the efficacy of hydrophilic polymers in a solid dispersion formulation in improving the solubility and dissolution rate of rivaroxaban (RXB), a poorly soluble drug. The developed solid dispersion consisted of two components, a drug and a polymer, and the drug was dispersed as amorphous particles in a polymer matrix using the spray drying method. Polymeric solid dispersions were evaluated using solubility tests, in vitro dissolution tests, powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and particle size distribution analysis. To maximize physical stability against crystallization and improve the solubility and dissolution of RXB, it is important to select the appropriate polymer type and the optimal ratio of the polymer to the drug. The optimized polyvinyl alcohol (PVA)-based (1/0.5, w/w) and gelatin-based (1/5, w/w) solid dispersion formulations showed 6.3 and 3.6 times higher drug solubilities than pure RXB powder, respectively, and the final dissolution rate was improved by approximately 1.5 times. Scanning electron microscopy and particle size distribution analyses confirmed that the gelatin-based solid dispersion was smaller and more spherical than the PVA-based solid dispersion, suggesting that the gelatin-based solid dispersion had a faster initial dissolution rate. Differential scanning calorimetry and powder X-ray diffraction analyses confirmed that RXB had successfully changed from a crystalline form to an amorphous form, contributing to the improvement in its solubility and dissolution rate. This study provides a strategy for selecting suitable polymers for the development of amorphous polymer solid dispersions that can overcome precipitation during dissolution and stabilization of the amorphous state. In addition, the selected polymer solid dispersion improved the drug solubility and dissolution rate of RXB, a poorly soluble drug, and may be used as a promising drug delivery system.


Assuntos
Polímeros , Rivaroxabana , Varredura Diferencial de Calorimetria , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Gelatina , Preparações Farmacêuticas , Polímeros/química , Pós/química , Solubilidade , Água/química , Difração de Raios X
13.
Artigo em Inglês | MEDLINE | ID: mdl-35993995

RESUMO

The aqueous solubility of active drug moiety plays a crucial role in the development of an efficacious formulation. The poor aqueous solubility of BCS class II and IV drugs is manifested as poor bioavailability. Preparation of cyclodextrin inclusion complex to improve the solubility, stability, and bioavailability is a well-established technique. The latest trend in cyclodextrin research is focused on ternary complexes wherein an auxiliary agent such as water-soluble polymers, organic ions, metals, or amino acids is incorporated in the inclusion complex. The cyclodextrin-based supramolecular ternary complex offers significant advantages over binary complex specifically for oral drug delivery. Compared with the binary complex, the ternary complex exhibits better complexation efficiency and stability constant. Moreover, the ternary complex has a major advantage of reducing the concentration of cyclodextrin required to achieve maximum solubility and stability. Lately, in silico molecular modeling has gained tremendous attention as a preliminary tool to evaluate the cyclodextrin-based ternary or binary complex which has been discussed. This review gives an insight into various ternary agents explored worldwide, significant observations, safety, and clinical studies carried out on ternary cyclodextrin complexes.


Assuntos
Ciclodextrinas , beta-Ciclodextrinas , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Ciclodextrinas/química , Estabilidade de Medicamentos , Humanos , Preparações Farmacêuticas/química , Solubilidade , Água/química , beta-Ciclodextrinas/química
14.
AAPS PharmSciTech ; 23(6): 219, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945468

RESUMO

Paclitaxel (PTX) is a hydrophobic chemotherapeutic agent cytotoxic against many serious cancers. This study aimed at designing novel PTX nanocrystals (PTX-NCs) coated with the biocompatible and biodegradable hydroxypropyl-beta-cyclodextrin (HPßCD) polymer with specific characteristics through the formation of a non-inclusion complex. Briefly, PTX-NCs were prepared by the anti-solvent method followed by homogenization. Then, the surface of the prepared PTX-NCs was modified using the HPßCD coat (HPßCD-PTX-NCs). The prepared nanocrystals, both coated and uncoated, were characterized in terms of size, polydispersity index, charge, morphology, and stability. Moreover, the nanocrystals were investigated using powder X-ray diffraction (PXRD), differential scanning calorimeter (DSC), and Fourier transform infrared spectroscopy (FTIR). As well, the in vitro release of PTX from the nanocrystals was determined under conditions similar to the IV route of administration. Furthermore, the tendency of the nanocrystals to induce hemolysis was investigated. Results indicated that the size was about 241.4 and 310.5 nm, the polydispersity index was 0.14 and 0.21, and the zeta potential was about - 22.6 and - 16.4 mV for PTX-NCs and HPßCD-PTX-NCs, respectively. Additionally, the PXRD, FTIR, and DSC profiles can be explained by the NCs' integrity and coat formation. The SEM images showed that both PTX-NCs and HPßCD-PTX-NCs have rod-like structures. Moreover, HPßCD-PTX-NCs had significantly superior in vitro release than both PTX-NCs and PTX. Interestingly, the hemolytic assay showed that HPßCD-PTX-NCs had a more efficient and safer profile than PTX-NCs. This study emphasized that HPßCD could be an interesting candidate for the surface modification of PTX-NCs providing superior properties such as release and safety profiles.


Assuntos
Nanopartículas , Paclitaxel , 2-Hidroxipropil-beta-Ciclodextrina , Varredura Diferencial de Calorimetria , Nanopartículas/química , Paclitaxel/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
15.
J Vis Exp ; (186)2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-36036623

RESUMO

Lipid-based excipients (LBEs) are low-toxic, biocompatible, and natural-based, and their application supports the sustainability of pharmaceutical manufacturing. However, the major challenge is their unstable solid-state, affecting the stability of the pharmaceutical product. Critical physical properties of lipids for their processing-such as melt temperature and viscosity, rheology, etc.-are related to their molecular structure and their crystallinity. Additives, as well as thermal and mechanical stress involved in the manufacturing process, affect the solid-state of lipids and thus the performance of pharmaceutical products thereof. Therefore, understanding the alteration in the solid-state is crucial. In this work, the combination of powder x-ray diffraction and differential scanning calorimetry (DSC) is introduced as the gold standard for the characterization of lipids' solid state. X-ray diffraction is the most efficient method to screen polymorphism and crystal growth. The polymorphic arrangement and the lamella length are characterized in the wide- and small-angle regions of x-ray diffraction, respectively. The small-angle x-ray scattering (SAXS) region can be further used to investigate crystal growth. Phase transition and separation can be indicated. DSC is used to screen the thermal behavior of lipids, estimate the miscibility of additives and/or active pharmaceutical ingredients (API) in the lipid matrix, and provide phase diagrams. Four case studies are presented in which LBEs are either used as a coating material or as an encapsulation matrix to provide lipid-coated multiparticulate systems and lipid nanosuspensions, respectively. The lipid solid-state and its potential alteration during storage are investigated and correlated to the alteration in the API release. Qualitative microscopical methods such as polarized light microscopy and scanning electron microscopy are complementary tools to investigate micro-level crystallization. Further analytical methods should be added based on the selected manufacturing process. The structure-function-processability relationship should be understood carefully to design robust and stable lipid-based pharmaceutical products.


Assuntos
Química Farmacêutica , Excipientes , Varredura Diferencial de Calorimetria , Estabilidade de Medicamentos , Excipientes/química , Lipídeos/química , Espalhamento a Baixo Ângulo , Difração de Raios X
16.
Colloids Surf B Biointerfaces ; 218: 112748, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35933887

RESUMO

We have comparatively studied the behavior of water molecules associated with the DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) bilayers in the presence and absence of ß-sitosteryl sulfate (PSO4) with the help of differential scanning calorimetry (DSC) and SAXS (small-angle x-ray scattering) techniques. The DSC heating endotherms were analyzed to understand the intermolecular interactions between water molecules and the lipid headgroups. The strongly bound, weakly bound, and free water (SB-Water, WB-Water, and FW-Water, respectively) were thus identified in the bilayers and the impact of incorporating PSO4 was evaluated. The SAXS data provided the supporting evidence for the impact of PSO4 on the intake of water into the bilayer. Regardless of the presence or absence of PSO4, the SB-Water existed in the system as the non-freezable fraction. On the other hand, the WB-Water and FW-Water fractions, both of which are freezable, exhibited freezing and melting behaviors that differed from each other significantly. The enthalpies of fusion of the WB-Water, which differed from that of the FW-Water, also varied with the mole fractions of PSO4. PSO4 enhanced the fraction of WB -water in the bilayer while at the same time reducing the fractions of SB-Water and FW-Water. The optimum retainability and the ease of release of the available water makes this system efficient for maintaining skin homeostasis if used in cosmetic and pharmaceutical formulations.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Bicamadas Lipídicas , 1,2-Dipalmitoilfosfatidilcolina/química , Varredura Diferencial de Calorimetria , Bicamadas Lipídicas/química , Preparações Farmacêuticas , Espalhamento a Baixo Ângulo , Sulfatos , Água/química , Difração de Raios X
17.
Soft Matter ; 18(35): 6703-6715, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36017811

RESUMO

The elucidation of the thermal properties of phosphatidylcholine liposomes is often based on the analysis of the thermal capacity profiles of multilamellar liposomes (MLV), which may qualitatively disagree with those of unilamellar liposomes (LUV). Experiments and interpretation of LUV liposomes is further complicated by aggregation and lamellarization of lipid bilayers in a short time period, which makes it almost impossible to distinguish the signatures of the two types of bilayers. To characterize independently MLV and LUV of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), the latter were prepared with the addition of small amounts of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) which, due to the sterical hindrance and negative charge at a given pH value, cause LUV repellence and contribute to their stability. Differential scanning calorimetry curves and temperature-dependent UV/Vis spectra of the prepared MLV and LUV were measured. Multivariate analysis of spectrophotometric data determined the phase transition temperatures (pretransition at Tp and the main phase transition at Tm), and based on the changes in turbidities, the thickness of the lipid bilayer in LUV was determined. The obtained data suggested that the curvature change is a key distinguishing factor in MLV and LUV heat capacity profiles. By combining the experimental results and those obtained by MD simulations, the interfacial water layer was characterized and its contribution to the thermal properties of LUV was discussed.


Assuntos
Fosfatidilcolinas , Lipossomas Unilamelares , 1,2-Dipalmitoilfosfatidilcolina/química , Varredura Diferencial de Calorimetria , Bicamadas Lipídicas/química , Lipossomos/química , Fosfatidilcolinas/química , Fosfatidilgliceróis , Suspensões , Lipossomas Unilamelares/química
18.
Molecules ; 27(14)2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35889235

RESUMO

Three-dimensional liquid crystal (LC) phases, cubic LC phases, have been extensively studied as fascinating molecular assembled systems formed by amphiphilic compounds. However, similar structures have only been seen in rare instances in lipid crystal states in glycolipid crystal studies. In this study, we prepared short-chain n-alkyl ß-D-glucosides (CnG) with an alkyl chain length n ranging from 4 to 6 and investigated their crystal structures. First, differential thermal analysis (DTA) and thermogravimetric analysis (TG) measurements showed the formation of hydrated crystals for C4G and C5G, respectively. Second, the crystal structures of CnG (n = 4, 5, 6) in both anhydrous and hydrated states were examined using a temperature-controlled powder X-ray diffraction (PXRD) measurement. Both hydrate and anhydrous crystals of C4G and C5G with critical packing parameters (CPPs) less than 0.33 formed cubic crystal phases. Bilayer lengths, calculated from the main diffraction peaks in each PXRD profile, depended on crystalline moisture for C5G, but no significant change was confirmed for C4G, indicating that the properties of each hydrophilic layer differ. However, C6G with a CPP of 0.42 formed a crystal structure with a modulated lamellar structure similar to C7G and C8G with similar CPP values. Thus, a glycolipid motif concept with a cubic crystal structure was demonstrated.


Assuntos
Glucosídeos , Cristais Líquidos , Varredura Diferencial de Calorimetria , Glucosídeos/química , Glicolipídeos , Difração de Raios X
19.
Molecules ; 27(14)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35889298

RESUMO

The study aims to assess the interaction between fluconazole and sulfonatocalix[4]naphthalene towards enhancing its dissolution performance and antimycotic activity. A solubility study was carried out at different pH conditions, and the results revealed the formation of a 1:1 molar ratio fluconazole-sulfonatocalix[4]naphthalene inclusion complex with an AL type phase solubility diagrams. The solid powder systems of fluconazole-sulfonatocalix[4]naphthalene were prepared using kneaded and co-evaporation techniques and physical mixtures. DCS, PXRD, TGA-DTG, FT-IR, and in vitro dissolution performance characterize the prepared systems. According to physicochemical characterization, the co-evaporation approach produces an amorphous inclusion complex of the drug inside the cavity of sulfonatocalix[4]naphthalene. The co-evaporate product significantly increased the drug dissolution rate up to 93 ± 1.77% within 10 min, unlike other prepared solid powders. The antimycotic activity showed an increase substantially (p ≤ 0.05, t-test) antimycotic activity of fluconazole co-evaporate mixture with sulfonatocalix[4]naphthalene compared with fluconazole alone against clinical strains of Candida albicans and Candida glabrata. In conclusion, sulfonatocalix[4]naphthalene could be considered an efficient complexing agent for fluconazole to enhance its aqueous solubility, dissolution performance, and antimycotic activity.


Assuntos
Fluconazol , beta-Ciclodextrinas , Varredura Diferencial de Calorimetria , Fluconazol/farmacologia , Naftalenos/farmacologia , Pós , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , beta-Ciclodextrinas/química
20.
Molecules ; 27(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35889394

RESUMO

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble ß-cyclodextrin-epichlorohydrin (ß-CD), as an effective drug carrier to enhance the poor solubility and bioavailability of galangin (GAL), a poorly water-soluble model drug. In this regard, inclusion complexes of GAL/ß-CDP were prepared. UV-VIS spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), zeta potential analysis, particle size analysis, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) were applied to characterize the synthesized GAL/ß-CD. Michigan Cancer Foundation-7 (MCF-7; human breast cancer cells) and rat embryo fibroblast (REF; normal cells) were employed to examine the in vitro cytotoxic effects of GAL/ß-CD using various parameters. The dye-based tests of MTT and crystal violet clearly exhibited that GAL/ß-CD-treated cells had a reduced proliferation rate, an influence that was not found in the normal cell line. The cells' death was found to follow apoptotic mechanisms, as revealed by the dye-based test of acridine orange/ethidium bromide (AO/EtBr), with the involvement of the mitochondria via caspase-3-mediated events, as manifested by the Rh 123 test. We also included a mouse model to examine possible in vivo toxic effects of GAL/ß-CD. It appears that the inclusion complex does not have a significant influence on normal cells, as indicated by serum levels of kidney and liver enzymatic markers, as well as thymic and splenic mass indices. A similar conclusion was reached on the histological level, as manifested by the absence of pathological alterations in the liver, kidney, thymus, spleen, heart, and lung.


Assuntos
Neoplasias da Mama , beta-Ciclodextrinas , Animais , Neoplasias da Mama/tratamento farmacológico , Varredura Diferencial de Calorimetria , Portadores de Fármacos , Feminino , Flavonoides , Humanos , Camundongos , Ratos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química , Difração de Raios X , beta-Ciclodextrinas/química
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