Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur J Pharm Biopharm ; 125: 106-113, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29329817

RESUMO

Various stability indicating techniques find application in the early stage development of novel therapeutic protein candidates. Some of these techniques are used to select formulation conditions that provide high protein physical stability. Such approach is highly dependent on the reliability of the stability indicating technique used. In this work, we present a formulation case study in which we evaluate the ability of differential scanning fluorimetry (DSF) and isothermal chemical denaturation (ICD) to predict the physical stability of a model monoclonal antibody during accelerated stability studies. First, we show that a thermal denaturation technique like DSF can provide misleading physical stability rankings due to buffer specific pH shifts during heating. Next, we demonstrate how isothermal chemical denaturation can be used to tackle the above-mentioned challenge. Subsequently, we show that the concentration dependence of the Gibbs free energy of unfolding determined by ICD provides better predictions for the protein physical stability in comparison to the often-used Tm (melting temperature of the protein determined with DSF) and Cm (concentration of denaturant needed to unfold 50% of the protein determined with ICD). Finally, we give a suggestion for a rational approach which includes a combination of DSF and ICD to obtain accurate and reliable protein physical stability ranking in different formulations.


Assuntos
Anticorpos Monoclonais/química , Fluorometria/métodos , Imunoglobulina G/química , Imunoglobulina G/metabolismo , Desnaturação Proteica , Anticorpos Monoclonais/análise , Varredura Diferencial de Calorimetria/métodos , Varredura Diferencial de Calorimetria/normas , Relação Dose-Resposta a Droga , Fluorometria/normas , Previsões , Guanidina/farmacologia , Humanos , Imunoglobulina G/análise , Desnaturação Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Reprodutibilidade dos Testes
2.
Food Res Int ; 99(Pt 1): 476-484, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28784508

RESUMO

The polymorphic crystallization and transformation behavior of extra virgin olive oil (EVOO) was examined by using differential scanning calorimetry (DSC) and X-ray diffraction with both laboratory-scale (XRD) and synchrotron radiation source (SR-XRD). The complex behavior observed was studied by previously analyzing mixtures composed by its main 2 to 6 triacylglycerol (TAG) components. Thus, component TAGs were successively added to simulate EVOO composition, until reaching a 6 TAGs mixture, composed by trioleoyl glycerol (OOO), 1-palmitoyl-2,3-dioleoyl glycerol (POO), 1,2-dioleoyl-3-linoleoyl glycerol (OOL), 1-palmitoyl-2-oleoyl-3-linoleoyl glycerol (POL), 1,2-dipalmitoyl-3-oleoyl glycerol (PPO) and 1-stearoyl-2,3-dioleoyl glycerol (SOO). Molten samples were cooled from 25°C to -80°C at a controlled rate of 2°C/min and subsequently heated at the same rate. The polymorphic behavior observed in multicomponent TAG mixtures was interpreted by considering three main groups of TAGs with different molecular structures: triunsaturated OOO and OOL, saturated-unsaturated-unsaturated POO, POL and SOO, and saturated-saturated-unsaturated PPO. As confirmed by our previous work, TAGs belonging to the same structural group displayed a highly similar polymorphic behavior. EVOO exhibited two different ß'-2L polymorphic forms (ß'2-2L and ß'1-2L), which transformed into ß'-3L when heated. Equivalent polymorphic pathways were detected when the same experimental conditions were applied to the 6 TAG components mixture. Hence, minor components may not exert a strong influence in this case.


Assuntos
Varredura Diferencial de Calorimetria , Cristalografia por Raios X , Análise de Alimentos/métodos , Azeite de Oliva/química , Trioleína/química , Varredura Diferencial de Calorimetria/normas , Cristalização , Cristalografia por Raios X/normas , Análise de Alimentos/normas , Fraude , Azeite de Oliva/normas , Transição de Fase , Controle de Qualidade , Síncrotrons , Temperatura de Transição , Trioleína/normas
3.
J Pharm Biomed Anal ; 86: 92-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23995752

RESUMO

Differential Scanning Calorimetry and Raman spectroscopy are both powerful tools used heavily in pharmaceutical development. For many studies such as polymorph characterization these two techniques are complimentary and provide data on different yet important aspects of material properties when combined together. In this work we describe an integrated Raman-DSC technology that simultaneously generates both DSC thermogram and Raman spectra of the pharmaceutical material being studied. The integrated system consists of a DSC with a Raman fiber optic probe inserted right on top of the sample furnace. The technology integrates synchronized Raman acquisition into DSC scan, enabling collection of molecular and structural information coupled with observation of thermal events. We first establish the technology by optimizing the instrumental set-up that offers relatively high-quality results for simultaneous DSC and Raman data collection. We then demonstrate the application of the technology by studying the polymorphs of d-mannitol, a common pharmaceutical excipient and BMS-A, an investigational drug candidate that exhibits multiple coexisting polymorphs. In both cases, the Raman-DSC technology was able to provide valuable information on the process of phase change and polymorph identification. Although similar information may be obtained by using various characterization techniques together, the integrated Raman-DSC indicated special advantages for industrial development such as high efficiency, material sparing and comprehensive data analysis. Moreover the technology provides an alternative to better correlate real-time phase behavior to molecular understanding. The technology thus has the potential to be used for Process Analytical Technology (PAT) purpose.


Assuntos
Descoberta de Drogas/normas , Análise Espectral Raman/normas , Varredura Diferencial de Calorimetria/métodos , Varredura Diferencial de Calorimetria/normas , Descoberta de Drogas/métodos , Manitol/análise , Manitol/química , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Análise Espectral Raman/métodos
4.
J Pharm Biomed Anal ; 70: 188-93, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22795312

RESUMO

Due to the physical-chemical and therapeutic impacts of polymorphism, its monitoring in raw materials is necessary. The purpose of this study was to develop and validate a quantitative method to determine the polymorphic content of nimodipine (NMP) raw materials based on differential scanning calorimetry (DSC). The polymorphs required for the development of the method were characterized through DSC, X-ray powder diffraction (XRPD) and Raman spectroscopy and their polymorphic identity was confirmed. The developed method was found to be linear, robust, precise, accurate and specific. Three different samples obtained from distinct suppliers (NMP 1, NMP 2 and NMP 3) were firstly characterized through XRPD and DSC as polymorphic mixtures. The determination of their polymorphic identity revealed that all samples presented the Modification I (Mod I) or metastable form in greatest proportion. Since the commercial polymorph is Mod I, the polymorphic characteristic of the samples analyzed needs to be investigated. Thus, the proposed method provides a useful tool for the monitoring of the polymorphic content of NMP raw materials.


Assuntos
Bloqueadores dos Canais de Cálcio/química , Varredura Diferencial de Calorimetria , Nimodipina/química , Análise de Variância , Calibragem , Varredura Diferencial de Calorimetria/normas , Cristalização , Cristalografia por Raios X , Limite de Detecção , Modelos Lineares , Difração de Pó , Reprodutibilidade dos Testes , Análise Espectral Raman
5.
Langmuir ; 27(12): 7714-21, 2011 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-21612233

RESUMO

The interaction of poly(methylaminophosphazene) hydrochloride (PMAP·HCl) of varying degrees of ionization (f) with the potassium salt of ι-carrageenan was studied by high-sensitivity differential scanning calorimetry at a KCl concentration of 0.15 M, which is included for the purpose of stabilizing the helix conformation of the polysaccharide up to 55 °C. The conditions of strong (pH 3.8, I = 0.15), moderate (pH 7.4, I = 0.15), and weak (pH 7.4, I = 0.25) electrostatic interactions of the polyelectrolytes were considered. The thermodynamic parameters of the helix-coil transition of ι-carrageenan were determined as a function of the polycation/polyanion ratio. We show that the interpolyelectrolyte reaction between PMAP·HCl and ι-carrageenan results in a complete unfolding of the polysaccharide helix under conditions of strong electrostatic interaction and increases its stability under conditions of medium and weak electrostatic interactions. The formation of stoichiometric PMAP-carrageenan interpolyelectrolyte complexes proceeded via a cooperative mechanism at pH 3.8 (f = 0.5) and pH 7.4 (f = 0.2) at an ionic strength of 0.15. In contrast, the complexation at pH 7.4 and an ionic strength of 0.25 could be considered to be a consecutive competitive binding of charged units of poly(methylaminophosphazene) to the oppositely charged polysaccharide matrix in the helix or coil conformation. Binding constants of the polycation to the helix and coil forms of ι-carrageenan were estimated. They revealed a preferential binding of the polycation to the helix form of the polysaccharide.


Assuntos
Varredura Diferencial de Calorimetria/normas , Carragenina/química , Eletrólitos/química , Compostos Organofosforados/química , Polímeros/química , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Concentração Osmolar , Espectrofotometria Infravermelho , Eletricidade Estática
6.
AAPS PharmSciTech ; 12(2): 693-704, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21598082

RESUMO

The focus of this investigation was to prepare the cocrystal of carbamazepine (CBZ) using nicotinamide as a coformer and to compare its preformulation properties and stability profile with CBZ. The cocrystal was prepared by solution cooling crystallization, solvent evaporation, and melting and cryomilling methods. They were characterized for solubility, intrinsic dissolution rate, chemical identification by Fourier transform infrared spectroscopy, crystallinity by differential scanning calorimetry, powder X-ray diffraction, and morphology by scanning electron microscopy. Additionally, mechanical properties were evaluated by tensile strength and Heckel analysis of compacts. The cocrystal and CBZ were stored at 40°C/94% RH, 40°C/75% RH, 25°C/60% RH, and 60°C to determine their stability behavior. The cocrystals were fluffy, with a needle-shaped crystal, and were less dense than CBZ. The solubility profiles of the cocrystals were similar to CBZ, but its intrinsic dissolution rate was lower due to the high tensile strength of its compacts. Unlike CBZ, the cocrystals were resistant to hydrate transformation, as revealed by the stability studies. Plastic deformation started at a higher compression pressure in the cocrystals than CBZ, as indicated by the high yield pressure. In conclusion, the preformulation profile of the cocrystals was similar to CBZ, except that it had an advantageous resistance to hydrate transformation.


Assuntos
Carbamazepina/química , Força Compressiva , Niacinamida/química , Resistência à Tração , Varredura Diferencial de Calorimetria/normas , Carbamazepina/normas , Cristalização/métodos , Cristalização/normas , Cristalografia por Raios X/normas , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/normas , Estabilidade de Medicamentos , Niacinamida/normas , Estresse Mecânico
7.
Biophys Chem ; 107(2): 189-95, 2004 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-14962599

RESUMO

The novel differential scanning calorimetry method as a technique for determining human red cell volume during freezing process has been reexamined and has been shown to provide a final erythrocyte volume to be 53% of its isotonic value after freezing from 0 to -40 degrees C. A new type of electronic particle counter (Multisizer 3, Beckman Coulter Inc., USA) was used to measure cell volume changes in response to equilibration in anisotonic media, and which gave out an equilibrated volume to be 57% of cell isotonic value in solution of 3186 mOsm. Both of these results indicate that 34-40% of intracellular water is trapped and is unavailable for participation in osmotic shifts. These findings are consistent with the published data that at least 20-32% (v/v) of the isotonic cell water is retained within RBCs. Then the application of trapped water in both simulation of freezing models and freezing-drying control was pointed out.


Assuntos
Criopreservação/métodos , Eritrócitos/citologia , Água/metabolismo , Preservação de Sangue , Varredura Diferencial de Calorimetria/normas , Tamanho Celular , Congelamento , Humanos , Soluções Isotônicas , Matemática , Osmose , Temperatura
8.
Cryo Letters ; 23(4): 229-36, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12391483

RESUMO

A modified analytical and experimental method using differential scanning calorimeter (DSC) was developed to determine the cell volume change during the freezing process. Two cell types were used in the study: human platelets and erythrocytes (red blood cells). Isotonic cell suspensions with different cytocrits were prepared and used in the DSC experiments. Low cooling rates were used to avoid intracellular ice formation. Cell suspensions were cooled from room temperature to -40 degrees C. Latent heat release from the freezing of cell suspensions was shown to be a linear function of cytocrit. From slope and intercept of the linear function, cell volume change was determined based on a developed theoretical model. From experimental data and theoretical analyses, it was revealed that (a) the final volume of a human platelet at -40 degrees C was 33.7% of its isotonic volume, and 15.2% of the original (at isotonic condition) intracellular water remained unfrozen inside platelets, and (b) the final volume of human erythrocyte at -40 degrees C was 50.0% of its isotonic volume, and 30.3% of the original intracellular water was kept inside cells as residual unfrozen water.


Assuntos
Plaquetas/citologia , Varredura Diferencial de Calorimetria/normas , Criopreservação , Eritrócitos/citologia , Tamanho Celular , Humanos , Reprodutibilidade dos Testes
9.
Bioconjug Chem ; 12(3): 372-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11353534

RESUMO

The level of conjugation of diethylenetriaminepentaacetic acid (DTPA) to the polysaccharide sodium hyaluronan (HA) has been measured by a colorimetric assay, isothermal titration calorimetry (ITC), and (1)H NMR spectroscopy. The colorimetric assay is based on the red shift, upon complexation with gadolinium ion (Gd3+), of the wavelength of maximum absorption of the dye arsenazo III. It can be performed in a few minutes using as little as 10 microg of polymer with a detection limit of approximately 0.03 mmol of DTPA (gram of polymer)-1. The ITC measurements yield values of the amount of DTPA linked to HA identical to those obtained by colorimetry. The levels of DTPA conjugation calculated by integration of signals at 3.1-3.2 ppm (DTPA protons) and at 2.0 ppm (HA acetamide protons) in the 1H NMR spectrum of HA-DTPA are consistently overestimated by a factor of approximately 2, compared to the data obtained by ITC and colorimetry. The longer relaxation times of protons of the polymer backbone, compared to those of protons attached to the freely moving DTPA side-chains may account for the discrepancy.


Assuntos
Ácido Hialurônico/química , Ácido Pentético/análise , Polímeros/química , Varredura Diferencial de Calorimetria/normas , Colorimetria/normas , Gadolínio , Espectroscopia de Ressonância Magnética/normas , Ácido Pentético/química , Polímeros/análise , Reprodutibilidade dos Testes , Solubilidade , Titulometria , Água
12.
J Pharm Biomed Anal ; 7(12): 1421-33, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2490527

RESUMO

Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) are commonly used for purity and solvent determinations, polymorphism studies and quantitative analysis. These methods are now simple to carry out. Furthermore, automation with robotics allows the use of DSC as a routine control. It is proposed to introduce DSC and TGA in pharmacopoeial monographs as a replacement or alternative to routine melting-point determinations and loss on drying assays. Furthermore, polymorphism and purity may be determined, which is often lacking in monographs. Results of many commercial batches or reference substances of pharmacopoeial raw materials and examples of the use of DSC robotics for quality control are given.


Assuntos
Varredura Diferencial de Calorimetria/métodos , Preparações Farmacêuticas/análise , Termogravimetria/métodos , Varredura Diferencial de Calorimetria/normas , Farmacopeias como Assunto , Robótica , Espectrometria de Fluorescência , Termogravimetria/normas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...