RESUMO
Praziquantel (PZQ) is a highly effective low-cost anthelmintic agent used as the first-choice treatment against schistosomiasis. The low solubility of the active is a major drawback for pharmaceutical formulation. A valid approach of the pharmaceutical industry for the improvement of the pharmacotechnical features of the active principles (such as solubility, processability, stability, among others), is the preparation of new solid forms, such as salts, polymorph, and pseudo-polymorph. Herein we report the preparation and characterization of a new solid form PZQ. The PZQ monohydrate (PZQ-MH) was prepared by a solventless procedure from the commercial racemate and the product was characterized at the solid-state employing optical digital microscopy, thermal methods (melting point, differential scanning calorimetry and thermogravimetric analysis), as well as and mid-infrared and near infrared spectroscopies. The chemical structure and content of water were full assessed by 1H nuclear magnetic resonance (NMR) in solution. The amount of water in PZQ-was also determined by different approaches, including thermogravimetric analysis and the loss on drying test. Solid-state 13C NMR (ssNMR) and X-ray powder diffraction (XRPD) completed the structural characterization of the new monohydrate. PZQ-MH showed a crystalline behavior during XRPD experiments and showed relevant differences in spectroscopic, calorimetric, ssNMR and XRPD signals when it was compared with the known crystal (Form A) and amorphous forms of PZQ. The determination of the intrinsic dissolution rate (IDR) of PZQ-MH was carried out as a functional characterization, observing that the new form had slightly higher IDR than Form A.
Assuntos
Anti-Helmínticos/química , Formas de Dosagem , Praziquantel/química , Varredura Diferencial de Calorimetria , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Difração de Pó , Espectroscopia de Prótons por Ressonância Magnética , SolubilidadeRESUMO
The aim of this study was to synthetize cocrystals of nateglinide, an antidiabetic agent of biopharmaceutics classification system Class IIa, as a strategy to improve both the solubility and the dissolution rate of the drug. Benzamide was selected by a screening procedure as a suitable coformer, and binary mixtures with different compositions were prepared and analyzed by differential scanning calorimetry (DSC). An in-depth analysis of DSC data allowed obtaining both the eutectic mixture and cocrystal compositions. The rationale of such an analysis was highlighted and explained. Cocrystals were prepared by kneading and solvent evaporation. Their formation was proved by DSC and confirmed by X-ray powder diffraction, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. The functional groups involved in the interaction leading to cocrystals formation were investigated by spectroscopic techniques. The in vitro dissolution profiles show that cocrystals have definite better pharmaceutical performances than the pure drug.
Assuntos
Varredura Diferencial de Calorimetria , Química Farmacêutica/métodos , Hipoglicemiantes/farmacocinética , Nateglinida/farmacocinética , Administração Oral , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Hipoglicemiantes/análise , Hipoglicemiantes/química , Nateglinida/análise , Nateglinida/química , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
The present study reports a high-throughput screening method for the salt formation of amine-containing active pharmaceutical ingredients (APIs) based on fluorescence measurements. A free form amine API was alkynylated by a solid-vapor reaction using propargyl bromide, and a fluorescent compound was produced by a subsequent reaction using 9-azidomethylanthracene. In contrast, salts were inert to propargyl bromide; thus, no fluorescence was observed. Samples for salt screening were prepared by grinding haloperidol with various counter acids, and these mixtures were derivatized in a 96-well microplate to determine whether the salt formation had occurred between haloperidol and the counter acids. Samples that turned into fluorescent and nonfluorescent were confirmed to be free form and salt form, respectively, using powder X-ray diffraction and Raman spectroscopy. In conclusion, our method adequately functions as an indicator of the salt formation of amine APIs. Further, this method allows for the rapid evaluation of the salt formation of APIs using 96-well microplates without the need for special reagents or techniques; thus, it is valuable for the discovery of an optimal salt form of newly developed amine APIs in the pharmaceutical industry.
Assuntos
Aminas/química , Preparações Farmacêuticas/química , Sais/análise , Espectrometria de Fluorescência/métodos , Difração de Pó , Espectrometria de Fluorescência/economia , Análise Espectral Raman , Difração de Raios XRESUMO
The aim of the present work was to establish a reliable analytical method to determine the degree of complexation in commercial metal proteinates used as feed additives in the solid state. Two complementary techniques were developed. Firstly, a quantitative attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopic method investigated modifications in vibrational absorption bands of the ligand on complex formation. Secondly, a powder X-ray diffraction (PXRD) method to quantify the amount of crystalline material in the proteinate product was developed. These methods were developed in tandem and cross-validated with each other. Multivariate analysis (MVA) was used to develop validated calibration and prediction models. The FTIR and PXRD calibrations showed excellent linearity (R2 > 0.99). The diagnostic model parameters showed that the FTIR and PXRD methods were robust with a root mean square error of calibration RMSEC ≤3.39% and a root mean square error of prediction RMSEP ≤7.17% respectively. Comparative statistics show excellent agreement between the MVA packages assessed and between the FTIR and PXRD methods. The methods can be used to determine the degree of complexation in complexes of both protein hydrolysates and pure amino acids.
Assuntos
Ração Animal/análise , Cobre/análise , Aditivos Alimentares/análise , Proteínas/análise , Animais , Difração de Pó , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The risk of colorectal cancer in Indian patients with long-standing ulcerative colitis is high and similar to that in the West. Surveillance for dysplasia in these patients is therefore important. Recent studies and guidelines suggest an increasing role for chromoendoscopy-guided biopsy in surveillance for dysplasia. We report our experience with the technique of chromoendoscopy and an economical method of performing it. Reconstituting indigo carmine from a powder form rather than the dyes available commercially is a better economical alternative and should help make chromoendoscopy the standard of care for dysplasia surveillance across the country.
Assuntos
Colite Ulcerativa/patologia , Colonoscopia/economia , Colonoscopia/métodos , Análise Custo-Benefício , Biópsia Guiada por Imagem/economia , Biópsia Guiada por Imagem/métodos , Colite Ulcerativa/complicações , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Corantes , Redução de Custos , Humanos , Índigo Carmim , Difração de PóRESUMO
Drug nanocrystals have been widely accepted as potent formulations to overcome poor solubility, dissolution and bioavailability problems of hydrophobic drugs. The present study aimed to develop drug nanocrystals of ezetimibe (Eze), a model BCS class II and hypocholesterolemic drug using bottom up precipitation methods. D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), and L-ascorbic acid-2-glucoside (AA2G), were the two stabilizers whose potential in developing Eze nanocrystals was investigated. Particle size and zeta potential portrayed the potential of both the stabilizers in producing Eze nanocrystals. The optimized nanocrystal formulations were evaluated for in-vitro solubility, dissolution, solid state characters and in-vivo pharmacodynamic performance. The nanocrystal formulations remarkably increased the solubility of the drug (p<0.05 compared to pure drug). Pure drug could not dissolve more than 28.9% during the 60 min dissolution study whereas the drug nanocrystals prepared with AA2G and TPGS presented t90% at 41.33 ± 2.58 and 16.07 ± 2.32 min, respectively. The PXRD and DSC studies confirmed the retention of crystallinity and the SEM images indicated lack of aggregation in dried nanocrystals. The TPGS nanocrystals presented significantly superior pharmacodynamic activity upon oral administration. The current study corroborated TPGS nanocrystals to be a promising choice of formulation for the oral delivery of Eze.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Anticolesterolemiantes/farmacologia , Ezetimiba/farmacologia , Nanopartículas , Administração Oral , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/química , Varredura Diferencial de Calorimetria , Ezetimiba/administração & dosagem , Ezetimiba/química , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Difração de Pó , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Disintegration of finished dosage forms (FDF) and drug dissolution are fundamentally important processes that affect bioavailability. Established theories do not account for disintegration and usually assume sink conditions for drug dissolution that often do not apply. We present the theory to describe the disintegration of FDF with subsequent dissolution of liberated particles containing the active pharmaceutical ingredient (API) and its application using population data analysis. Population modeling, using dissolution profiles of 400mg cefditoren pivoxil tablets manufactured under various tableting pressures, characterized the intrinsic lifetime distribution of the particles and identified the presence of crystalline API in the formulation that was proven by X-ray diffraction. Modeling further estimated the disintegration time of FDF, the solubility of the amorphous API and its chemical instability in the medium that were in agreement with the experimentally determined values. This novel approach provides a quantitative understanding of the manufacturing process of FDF and can substantially contribute to the targeted development of finished dosage forms.
Assuntos
Modelos Químicos , Cefalosporinas/química , Química Farmacêutica , Formas de Dosagem , Difração de Pó , Pós , Solubilidade , Difração de Raios XRESUMO
Knowledge of the unit cell volume of a crystalline form and the expected space filling requirements of an API molecule can be used to determine if a crystalline material is likely to be multicomponent, such as a solvate, hydrate, salt, or a co-crystal. The unit cell information can be readily accessed from powder diffraction data alone utilizing powder indexing methodology. If the unit cell has additional space not likely attributable to the API entity, then there is either a void or another component within the crystal lattice. This "leftover" space can be used to determine the likely stoichiometry of the additional component. A simple approach for calculating the expected required volume for a given molecule within a crystal using an atom based additive approach will be discussed. Coupling this estimation with the actual unit cell volumes and space group information obtained from powder indexing allows for the rapid evaluation of the likely stoichiometry of multicomponent crystals using diffraction data alone. This approach is particularly useful for the early assessment of new phases during salt, co-crystal, and polymorph screening, and also for the characterization of stable and unstable solvates.
Assuntos
Difração de Pó/métodos , Difração de Raios X/métodos , Cristalização , Humanos , Estrutura MolecularRESUMO
There are no reports about the pharmaceutical applications of hupu gum (HG). Hence the present study was undertaken to test its suitability in the dissolution enhancement of poorly water soluble drug. Rofecoxib (RFB) was taken as model drug. For comparison solid mixtures were prepared with carriers such as poly vinyl pyrrolidone (PVP), sodium starch glycollate (SSG) and guar gum (GG). Physical mixing (PM), co-grinding (CG), kneading (KT) and solvent evaporation (SE) techniques were used to prepare the solid mixtures, using all the carriers in different carrier and drug ratios. The solid mixtures were characterized by powder X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR). There was a significant improvement in the dissolution rate of solid mixtures of HG, when compared with the solid mixtures of other carriers. There was an increase in dissolution rate with increase in concentration of HG upto 1:1 ratio of carrier and drug. No drug-carrier interaction was found by FTIR studies. XRD studies indicated reduction in crystallinity of the drug with increase in HG concentration. Hence HG could be a useful carrier for the dissolution enhancement of poorly water soluble drugs.
Assuntos
Bixaceae , Inibidores de Ciclo-Oxigenase 2/química , Portadores de Fármacos , Lactonas/química , Gomas Vegetais/química , Solventes/química , Sulfonas/química , Água/química , Química Farmacêutica , Cristalografia por Raios X , Cinética , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tecnologia Farmacêutica/métodosRESUMO
Total X-ray scattering and pair distribution function (PDF) analysis, using a high-energy synchrotron source, allow direct study of the short- and intermediate-range structure that distinguish amorphous, structurally disordered, and nanocrystalline biominerals. For such samples in which diffuse scatter is a significant component, care must be taken in the experimental procedures to optimize data quality and extract the useful signal necessary to calculate the PDF. General methods are described for data collection and processing, including commonly used software programs. Methods for analysis and interpretation of PDFs are presented, including direct real-space refinement and reverse Monte Carlo methods. Greater application of PDFs to amorphous and poorly crystallized biominerals will provide new insight into structure, especially over length scales that are not probed by other techniques. The rapid data collection available at synchrotron facilities also allows in situ kinetic studies of reactions involving biominerals.
Assuntos
Carbonato de Cálcio/química , Compostos Férricos/química , Ferritinas/química , Cinética , Método de Monte Carlo , Nanopartículas/química , Difração de Pó , Síncrotrons , Difração de Raios XRESUMO
During aqueous drug-layer coating, drug substance(s) are exposed to water and elevated temperatures which can lead to water-mediated process induced transformations (PITs). The effects of aqueous drug-layer coating of pellets (Cellets(®)) on the anhydrous piroxicam, PRX, were investigated in the miniaturized coating equipment and with free films. Hydroxypropyl methylcellulose (HPMC) was used as a carrier coating polymer. Free films were prepared by using an in-house small-scale rotating plate system equipped with an atomization air nozzle. Raman spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the solid-state properties and surface morphology of the pellets and free films. The results showed that anhydrous PRX form I (AH) and monohydrate (MH) were stable during drug-layer coating, but amorphous PRX in solid dispersion (SD) crystallized as MH already after 10 min of coating. Furthermore, the increase in a dissolution rate was achieved from the drug-layer coated inert pellets compared to powder forms. In conclusion, water-mediated solid-state PITs of amorphous PRX is evident during aqueous-based drug-layer coating of pellets, and solid-state change can be verified using Raman spectroscopy.
Assuntos
Anti-Inflamatórios não Esteroides/química , Metilcelulose/análogos & derivados , Piroxicam/química , Varredura Diferencial de Calorimetria , Composição de Medicamentos/métodos , Derivados da Hipromelose , Metilcelulose/química , Difração de Pó , Solubilidade , Análise Espectral Raman , Água/química , Difração de Raios XRESUMO
We report an economic method for synthesis of highly ordered silica with a mixing surfactant system containing short-chain cationic surfactant (decyltrimethyl ammonium bromide, denoted C10TMAB) and short-chain anionic surfactant (sodium octyl sulfate, denoted SOS) as the templating agents. Highly ordered supermicroporous silica was synthesized by judiciously chosen mixing ratio of surfactants. The samples were characterized by small-angle X-ray diffraction, transmission electron microscopy, and N2 adsorption-desorption. The results showed that the pore structure of the resulting silica belongs to the two-dimensional hexagonal structure (space group 2D-p6mm) with a pore size of ca. 2.2nm. Moreover, the method proposed herein is expected to facilitate the synthesis of not only porous silicas but also materials with other framework compositions.
Assuntos
Custos e Análise de Custo , Dióxido de Silício/síntese química , Microscopia Eletrônica de Transmissão , Difração de Pó , Espalhamento a Baixo ÂnguloRESUMO
The aim of this study was to gain understanding about the effects of different solid-state forms of a poorly water-soluble piroxicam on drug dissolution and oral bioavailability in rats. Three different solid-state forms of piroxicam were studied: anhydrate I (AH), monohydrate (MH), and amorphous form in solid dispersion (SD). In addition, the effect of a new polymeric excipient Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) on oral bioavailability of piroxicam was investigated. Significant differences in the dissolution and oral bioavailability were found between the solid-state forms of piroxicam. Amorphous piroxicam in SD showed the fastest dissolution in vitro and a solid-state transformation to MH in the dissolution medium. Despite the presence of solid-state transformation, SD exhibited the highest rate and extent of oral absorption in rats. Oral bioavailability of other two solid-state forms decreased in the order AH and MH. The use of Soluplus® was found to enhance the dissolution and oral bioavailability of piroxicam in rats. The present study shows the importance of solid-state form selection for oral bioavailability of a poorly water-soluble drug.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Piroxicam/farmacocinética , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/química , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Masculino , Piroxicam/sangue , Piroxicam/química , Difração de Pó , Ratos , Ratos Wistar , Solubilidade , Difração de Raios XRESUMO
PURPOSE: To understand the transformation pathways amongst anhydrate/hydrate solid forms of sodium naproxen and to highlight the importance of a polymorphic dihydrate within this context. METHODS: Multi-temperature dynamic vapour sorption (DVS) analysis combined with variable-humidity X-ray powder diffraction (XRPD) to establish the transformation pathways as a function of temperature and humidity. XRPD and thermogravimetric analysis (TGA) to characterise bulk samples. Monitoring of in-situ dehydration using solid-state (13)C CP/MAS spectroscopy. RESULTS: At 25 °C, anhydrous sodium naproxen (AH) transforms directly to one dihydrate polymorph (DH-II). At 50 °C, AH transforms stepwise to a monohydrate (MH) then to the other dihydrate polymorph (DH-I). DH-II transforms to a tetrahydrate (TH) more readily than DH-I transforms to TH. Both dihydrate polymorphs transform to the same MH. CONCLUSIONS: The properties of the polymorphic dihydrate control the transformation pathways of sodium naproxen.
Assuntos
Anti-Inflamatórios não Esteroides/química , Naproxeno/química , Água/química , Cristalização , Umidade , Difração de Pó , Sódio/química , Temperatura , Termogravimetria , Difração de Raios XRESUMO
Vapor-induced transformations of docetaxel anhydrous (form D(A)) under ambient conditions have been studied using methanol, ethanol, and water as the solvent media. The online vapor-induced transformations were monitored by powder X-ray diffractometry. New solid forms (solvates/hydrates/anhydrous) of docetaxel anhydrous were obtained in stoichiometric ratios which were characterized completely using powder X-ray diffraction, differential scanning calorimeter, thermogravimetric analysis, and spectroscopic ((13)C solid-state nuclear magnetic spectroscopy, solution (1)H NMR, and Fourier transform infrared) techniques. The new forms namely methanol solvate (D(M)), ethanol solvate (D(E)), monohydrate (D(MH)), trihydrate (D(TH)), and anhydrous (D(AN-I) and D(AN-II)) were identified through structural analysis.
Assuntos
Antineoplásicos/química , Transição de Fase , Taxoides/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cristalografia por Raios X , Docetaxel , Etanol/química , Espectroscopia de Ressonância Magnética , Metanol/química , Estrutura Molecular , Difração de Pó , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Tecnologia Farmacêutica/métodos , Termogravimetria , Volatilização , Água/químicaRESUMO
PURPOSE: The purpose of the research is to investigate the application of bagasse fly ash, a sugar industry solid waste for the synthesis of zeolites and their behavior for the sorption of p-nitrophenol (p-NP). METHODS: Zeolitic materials were prepared from bagasse fly ash using alkaline hydrothermal (CZBFA) and fusion (FZBFA) treatment. Comparative batch sorption studies of prepared zeolitic material and virgin material were undertaken to determine their capacities for removal of p-nitrophenol. RESULTS: PXRD patterns revealed that zeolite P and analcime were the dominant contents of synthesized zeolitic material. Chemical composition, morphology, and crystalline nature of CZBFA and FZBFA were characterized by XRF, FTIR, and SEM. The Langmuir, Freundlich, Dubinin Redushkwich, and Temkin sorption isotherms were applied to compare the sorption nature and capacity of synthesized CZBFA and FZBFA with virgin BFA. For each sorbent-p-NP system, a pseudo-second-order kinetic model described the sorption kinetics accurately. The thermodynamics of the p-NP-sorbent systems exhibit an exothermic sorption process. Intraparticle diffusion model shows that the sorption rate was controlled by film diffusion followed by pore diffusion. Regeneration of sorbents was carried out by desorption studies with HCl, NaOH, and SDS detergent. The column studies were performed for the practical utility of sorbents, and breakthrough curve were obtained, which exhibit higher sorption capacity than batch method. CONCLUSION: The sorption capacities of the synthesized zeolites had improved sorption capacities for the sequestration of p-NP and can be utilized as low-cost sorbents for treatment of p-nitrophenolic wastewater.
Assuntos
Cinza de Carvão/química , Nitrofenóis/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Zeolitas/química , Adsorção , Agricultura , Difusão , Resíduos Industriais/prevenção & controle , Cinética , Extração Líquido-Líquido , Microscopia Eletrônica de Varredura , Modelos Químicos , Difração de Pó , Saccharum/química , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Difração de Raios XRESUMO
The paper deals with the characterisation of the bioactive phenomena of glass-ceramic scaffold derived from Bioglass® (containing 77 wt.% of crystalline phases Na(2)O·2CaO·3SiO(2) and CaO·SiO(2) and 23 wt.% of residual glass phase) using simulated body fluid (SBF) buffered with tris-(hydroxymethyl) aminomethane (TRIS). A significant effect of the TRIS buffer on glass-ceramic scaffold dissolution in SBF was detected. To better understand the influence of the buffer, the glass-ceramic scaffold was exposed to a series of in vitro tests using different media as follows: (i) a fresh liquid flow of SBF containing tris (hydroxymethyl) aminomethane; (ii) SBF solution without TRIS buffer; (iii) TRIS buffer alone; and (iv) demineralised water. The in vitro tests were provided under static and dynamic arrangements. SBF buffered with TRIS dissolved both the crystalline and residual glass phases of the scaffold and a crystalline form of hydroxyapatite (HAp) developed on the scaffold surface. In contrast, when TRIS buffer was not present in the solutions only the residual glassy phase dissolved and an amorphous calcium phosphate (Ca-P) phase formed on the scaffold surface. It was confirmed that the TRIS buffer primarily dissolved the crystalline phase of the glass-ceramic, doubled the dissolving rate of the scaffold and moreover supported the formation of crystalline HAp. This significant effect of the buffer TRIS on bioactive glass-ceramic scaffold degradation in SBF has not been demonstrated previously and should be considered when analysing the results of SBF immersion bioactivity tests of such systems.
Assuntos
Materiais Biocompatíveis , Líquidos Corporais , Cerâmica , Vidro , Trometamina , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Difração de Pó , Espectrofotometria AtômicaRESUMO
The crystal structure of monohydrated trifolin (kaempferol 3-O-ß-D-galactopyranoside) (an important biologically active compound, which was isolated from the aerial part of Consolida oliveriana) has been determined from conventional laboratory X-ray powder diffraction data. Variable counting time technique was used during measurement and crystal structure was solved by means of Monte Carlo algorithm. The final structure was achieved by Rietveld refinement using both constraints and restraints on interatomic bond lengths and angles.
Assuntos
Medicamentos de Ervas Chinesas/química , Galactosídeos/química , Quempferóis/química , Ranunculaceae/química , Modelos Moleculares , Método de Monte Carlo , Difração de Pó , Difração de Raios XRESUMO
A variety of spectroscopic techniques combined with in situ pressure-controlled X-ray diffraction and molecular simulations have been utilized to characterize the five-step phase transition observed upon N(2) adsorption within the high-surface area metal-organic framework Co(BDP) (BDP(2-) = 1,4-benzenedipyrozolate). The computationally assisted structure determinations reveal structural changes involving the orientation of the benzene rings relative to the pyrazolate rings, the dihedral angles for the pyrazolate rings bound at the metal centers, and a change in the metal coordination geometry from square planar to tetrahedral. Variable-temperature magnetic susceptibility measurements and in situ infrared and UV-vis-NIR spectroscopic measurements provide strong corroborating evidence for the observed changes in structure. In addition, the results from in situ microcalorimetry measurements show that an additional heat of 2 kJ/mol is required for each of the first four transitions, while 7 kJ/mol is necessary for the last step involving the transformation of Co(II) from square planar to tetrahedral. Based on the enthalpy, a weak N(2) interaction with the open Co(II) coordination sites is proposed for the first four phases, which is supported by Monte Carlo simulations.
Assuntos
Nitrogênio/química , Compostos Organometálicos/química , Adsorção , Modelos Moleculares , Simulação de Dinâmica Molecular , Método de Monte Carlo , Difração de Pó , Propriedades de SuperfícieRESUMO
There is a need for thorough knowledge of solid-state transformations in order to implement quality by design (QbD) methodology in drug development. The present study was aimed at gaining a mechanistic understanding of the dehydration of nitrofurantoin monohydrate II (NF-MH). The dehydration was studied using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), and variable temperature X-ray powder diffraction (VT-XRPD). Isothermal TGA data were used to study dehydration kinetics using model-fitting and model-free approaches. Model-fitting analysis indicated a good fit for several models derived from nucleation-growth and/or geometric contraction mechanisms. However, based on visual observations during HSM, Avrami-Erofeyev equations A3 and A4, indicating nucleation-growth phenomenon, were found to be the most suitable kinetic models. HSM showed initiation of dehydration with random nucleation, and nuclei coalesced with the progress of dehydration reaction. VT-XRPD revealed formation of anhydrate beta form on dehydration of NF-MH. The phenomenon of random nucleation is justified based on the crystal structure of NF-MH, which showed presence of water molecules in an isolated manner, prohibiting directional dehydration. It was found that supplementary information from HSM and VT-XRPD can be valuable to gain a better understanding of dehydration from formal solid-state kinetics analysis.