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Drug Discovery Today. Technologies Jul 2018Solubility is a crucial physicochemical parameter affecting the whole process of drug discovery and development. Thus, understanding of the methods and concepts to... (Review)
Review
Solubility is a crucial physicochemical parameter affecting the whole process of drug discovery and development. Thus, understanding of the methods and concepts to measure and predict this propensity are of utmost importance for the pharmaceutical scientist. Despite their inherent limitations, kinetic solubility screening methods became routine assays by mimicking bioassay conditions and guiding the lead optimization process. In contrast, thermodynamic solubility methods show a clear evolution: miniaturized high throughput assays coupled to analytical techniques such as solid-state characterization, ultra performance liquid chromatography, or polychromatic turbidimetry, have been developed, thereby enabling a more complex physicochemical profiling at the early discovery stage. Solubility prediction still poses a significant challenge at the industrial level. Classification and critical evaluation of recent in silico models are provided. Discussion of experimental and computational methods: was based on relevant industrial references.
Topics: Chromatography, High Pressure Liquid; Drug Discovery; High-Throughput Screening Assays; Kinetics; Models, Chemical; Pharmaceutical Preparations; Powder Diffraction; Quantitative Structure-Activity Relationship; Solubility; Spectrophotometry, Ultraviolet; Thermodynamics
PubMed: 30103861
DOI: 10.1016/j.ddtec.2018.06.001 -
Acta Crystallographica. Section D,... Nov 2020This study focuses on the polymorphism of human insulin (HI) upon the binding of the phenolic derivatives p-coumaric acid or trans-resveratrol over a wide pH range. The...
This study focuses on the polymorphism of human insulin (HI) upon the binding of the phenolic derivatives p-coumaric acid or trans-resveratrol over a wide pH range. The determination of the structural behaviour of HI via X-ray powder diffraction (XRPD) and single-crystal X-ray diffraction (SCXRD) is reported. Four distinct polymorphs were identified, two of which have not been reported previously. The intermediate phase transitions are discussed. One of the novel monoclinic polymorphs displays the highest molecular packing among insulin polymorphs of the same space group to date; its structure was elucidated by SCXRD. XRPD data collection was performed using a variety of instrumental setups and a systematic comparison of the acquired data is presented. A laboratory diffractometer was used for screening prior to high-resolution XRPD data collection on the ID22 beamline at the European Synchrotron Radiation Facility. Additional measurements for the most representative samples were performed on the X04SA beamline at the Swiss Light Source (SLS) using the MYTHEN II detector, which allowed the detection of minor previously untraceable impurities and dramatically improved the d-spacing resolution even for poorly diffracting samples.
Topics: Coumaric Acids; Crystallization; Humans; Insulin, Regular, Human; Macromolecular Substances; Models, Molecular; Powder Diffraction; Protein Binding; Resveratrol; X-Ray Diffraction
PubMed: 33135678
DOI: 10.1107/S205979832001195X -
Journal of the Air & Waste Management... Nov 2020The random discharge of marine fish waste into the coast generates environmental pollution. However, a better valorization of these by-products leads to the extraction...
The random discharge of marine fish waste into the coast generates environmental pollution. However, a better valorization of these by-products leads to the extraction of sustainable biomolecules. Chitosan is a natural biopolymer that can be produced from various marine by-products, in particular the crustacean shells, crabs, and fish scales. The aim of this current study is the extraction of chitin and characterization of chitosan obtained after a deacetylation reaction from ( as a new marine source. The β form of chitin extracted undergoes deacetylation in 40% NaOH at 121°C for 20 min. The chemical structure of obtained chitosan was characterized based on Fourier transforms infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), Scanning electron microscope (SEM), and Energy-dispersive X-ray spectroscopy (EDS). The physicochemical properties of obtained chitosan such as the ash, moisture, nitrogen, solubility, molecular weight, fat, and water-binding capacity were also determined. According to the results of FTIR and XRD analysis, the degree of deacetylation (DDA), and the crystalline index (CrI) value of obtained chitosan is respectively about 87% and 95%. The SEM and EDS analysis revealed respectively fibrillar and pleated morphology with the presence of three major elements characterizing the chitosan, which are C, O, and N. The physicochemical analysis showed that the rate of ash, moisture, and nitrogen in obtained chitosan were respectively about 0.10, 0.34, and 7%. The solubility, molecular weight, fat, and water-binding capacity of produced chitosan were found to be 93%, 5.86 kDa, 310, and 510% respectively. scales could be considered a promising and alternative source of chitin and chitosan, which will be applicable in a large number of fields. : Direct rejection of marine biowaste as fish scales in nature, port, or fish processing plants, is a dramatic problem that is growing day after day. These uncontrollable discharges cause marine pollution and promote bacterial growth, which leads to a degradation of the soil and air quality. Taking into account the objectives of sustainable development, better development of these by-products would make it possible to produce valuable biomaterials that will be applied in various fields and which have benefits for the environment and humans. The central objective of this research is accentuated on the enhancement of scales; by the conversion of chitin into chitosan and the determination of its physicochemical characterization. The obtained chitosan from scales could be applied in the agricultural and food industry.
Topics: Acetylation; Animals; Chitin; Fishes; Microscopy, Electron, Scanning; Molecular Weight; Powder Diffraction; Solubility; Spectroscopy, Fourier Transform Infrared; Water; X-Ray Diffraction
PubMed: 32915095
DOI: 10.1080/10962247.2020.1813840 -
Chemical & Pharmaceutical Bulletin 2020A concise spherical granulation method is required to prepare extemporaneously granules remanufactured from oral dosage forms for administration to individuals who...
A concise spherical granulation method is required to prepare extemporaneously granules remanufactured from oral dosage forms for administration to individuals who cannot swallow tablets or capsules. In this study, we determined the feasibility of spherical granulation using a planetary centrifugal mixer. A model formulation, 20% ibuprofen (IBP) granules, was prepared using a lactose/cornstarch (7 : 3, w/w) mixture or D-mannitol as diluents, and changes in granule characteristics (mean diameter (d50), distribution range of granule size (span), and yield) were evaluated according to the amount of water added and the granulation time. The amount of water was assessed using the plastic limit value as measured using a digital force gauge. We successfully produced granules, and larger amounts of water and longer granulation times resulted in larger d50 values and smaller span values. The optimal granulation time was 45 s and the optimal water contents were 70 and 67.5% of the plastic limit value for the lactose/cornstarch mixture and D-mannitol, respectively. When compared to commercial 20% IBP granules, powder X-ray diffraction and differential scanning calorimetry analyses showed that the granulation process did not alter the crystallinity of the drug. Thus, this novel granulation method using a planetary centrifugal mixer may be a promising technique for compounding in pharmacies and in pharmaceutical manufacturing.
Topics: Calorimetry, Differential Scanning; Centrifugation; Ibuprofen; Lactose; Mannitol; Particle Size; Powder Diffraction; Starch; Surface Properties
PubMed: 32115532
DOI: 10.1248/cpb.c19-00888 -
Journal of Pharmaceutical Sciences Nov 2022Flubendazole (FBZ) is a poorly water-soluble drug, and different methodologies have been proposed to improve its oral bioavailability. Obtaining the amorphous drug phase...
Flubendazole (FBZ) is a poorly water-soluble drug, and different methodologies have been proposed to improve its oral bioavailability. Obtaining the amorphous drug phase is an alternative to improve its water solubility. Several techniques for drug amorphization, such as spray drying, lyophilization, melt quenching, solvent-evaporation, and ball milling, can yield various types of structural disorder and possibly render variations in physicochemical properties. Herein, we focus on evaluating the influence of the ball-milling process on the amorphization of FBZ. The characterization of the average global and local structures before, during, and after the milling process is described by sequential Rietveld refinements, pair distribution function analysis, and the Reverse Monte Carlo method. We show that preserving the local structure (nearest molecules) can be responsible for avoiding the fast structure recrystallization commonly observed when using the solvent-evaporation process for the studied drug.
Topics: Calorimetry, Differential Scanning; Drug Stability; Mebendazole; Powder Diffraction; Powders; Solubility; Solvents; Water; X-Ray Diffraction; X-Rays
PubMed: 35760122
DOI: 10.1016/j.xphs.2022.06.018 -
Pharmaceutical Development and... Feb 2019This study explores the preparation and investigation of dissolution properties of piroxicam cocrystals. Differential scanning calorimetry (DSC) was used to determine...
This study explores the preparation and investigation of dissolution properties of piroxicam cocrystals. Differential scanning calorimetry (DSC) was used to determine the capability of resorcinol (RES), methylparaben (MPB), and vanillin (VAN) to form cocrystals with piroxicam (PRX). Generation of cocrystals was attempted by liquid assisted grinding and slurry methods. Cocrystals were characterized by thermal methods, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. Apparent solubility, intrinsic dissolution rate (IDR), and powder dissolution profile of cocrystals were compared with anhydrous piroxicam, piroxicam monohydrate (PRXMH), and previously reported piroxicam-succinic acid cocrystal. Contact angles and particle sizes of the studied solids were also measured. Based on the DSC screening results, we prepared and characterized PRX-RES and PRX-MPB cocrystals. Interestingly, the cocrystals not only failed to improve apparent solubility and IDR of PRX but also showed lower values than PRX that were attributed to induction of phase transformation of PRX to PRXMH. In contrary, cocrystals performed better than PRX in powder dissolution studies. The higher dissolution rates of cocrystals were explained by improved wettability and reduced sizes. This study has highlighted the complexity of solid state properties of cocrystals and has provided new evidence for the in-solution stability issues of cocrystals.
Topics: Calorimetry, Differential Scanning; Crystallization; Particle Size; Phenol; Piroxicam; Powder Diffraction; Powders; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 29557714
DOI: 10.1080/10837450.2018.1455210 -
Journal of Pharmaceutical Sciences Nov 2019Prasugrel hydrochloride (PHCl) undergoes salt disproportionation, and the resulting prasugrel free base (PFB) may lead to the poor in vitro and or in vivo performance...
Prasugrel hydrochloride (PHCl) undergoes salt disproportionation, and the resulting prasugrel free base (PFB) may lead to the poor in vitro and or in vivo performance of the drug product. The aim of the present work was to develop univariate and multivariate models based on X-ray powder diffraction to quantify the salt and base in the powder and tablet formulations. Compositionally identical formulations of PHCl and PFB were prepared and mixed in various proportions to make 0%-30% PFB sample matrices. The formulations consisted of commonly used excipients, which are generally used in commercially available products. X-ray powder diffraction data were collected and subjected to the least square regression and partial least square regression analysis. The model performance parameters such as root mean squared and standard errors were low for univariate models compared to partial least square regression multivariate models. Model predicted values of the independent sample matrices by both methods matched closely with the actual values of PFB and PHCl. However, residual and standard deviation were low in univariate models predicted values. The models developed in this work have been shown to quantitate the PHCl disproportionation to PFB fraction in the drug product and provide a means to control the disproportionation of PHCl.
Topics: Chemistry, Pharmaceutical; Excipients; Powder Diffraction; Powders; Prasugrel Hydrochloride; Tablets; X-Ray Diffraction
PubMed: 31276685
DOI: 10.1016/j.xphs.2019.06.024 -
Acta Crystallographica. Section A,... Sep 2022A prototype application for machine-readable literature is investigated. The program is called pyDataRecognition and serves as an example of a data-driven literature...
A prototype application for machine-readable literature is investigated. The program is called pyDataRecognition and serves as an example of a data-driven literature search, where the literature search query is an experimental data set provided by the user. The user uploads a powder pattern together with the radiation wavelength. The program compares the user data to a database of existing powder patterns associated with published papers and produces a rank ordered according to their similarity score. The program returns the digital object identifier and full reference of top-ranked papers together with a stack plot of the user data alongside the top-five database entries. The paper describes the approach and explores successes and challenges.
Topics: Databases, Factual; Powder Diffraction; Powders; Publications
PubMed: 36047395
DOI: 10.1107/S2053273322007483 -
International Journal of Pharmaceutics Dec 2019A comprehensive cocrystal study for the insoluble natural pharmaceutical compound xanthotoxin (XT) was conducted, in which xanthotoxin-para aminobenzoic acid (XT-PABA)...
A comprehensive cocrystal study for the insoluble natural pharmaceutical compound xanthotoxin (XT) was conducted, in which xanthotoxin-para aminobenzoic acid (XT-PABA) and xanthotoxin-oxalic acid (XT-OA) cocrystals were obtained. The xanthotoxin cocrystals were characterized by powder X-ray diffraction, thermal analysis, and FT-IR spectra, and the crystal structures were determined by single-crystal X-ray diffraction. Crystal structures and thermal analysis showed that XT-OA was more stable than XT-PABA. Energy framework calculation indicated that H-bond and π···π interactions generated in XT-OA were stronger than that in XT-PABA and xanthotoxin. The powder dissolution experiments of xanthotoxin and its cocrystals suggested the XT-OA cocrystal might be applied as an alternative formulation of API, on account of its enhanced solubility and stability in the hydrochloric acid buffer solution (pH 1.2). The cocrystallization engineering can prolong the enhanced apparent solubility via modulating the stability.
Topics: 4-Aminobenzoic Acid; Crystallization; Crystallography, X-Ray; Drug Stability; Hydrogen Bonding; Methoxsalen; Oxalic Acid; Powder Diffraction; Powders; Solubility; X-Ray Diffraction
PubMed: 31678374
DOI: 10.1016/j.ijpharm.2019.118776 -
Journal of AOAC International Jul 2016Rifaximin is a gut-selective oral antimicrobial that has no systemic adverse effects compared with placebo. It is used for the treatment of hepatic encephalopathy,...
Rifaximin is a gut-selective oral antimicrobial that has no systemic adverse effects compared with placebo. It is used for the treatment of hepatic encephalopathy, traveler's diarrhea, irritable bowel syndrome, Clostridium difficile infection, ulcerative colitis, and acute diarrhea. The crystalline form present in rifaximin, α, has minimal systemic absorption compared to the amorphous form. The objective of this study was to obtain polymorphic forms of rifaximin using recrystallization processes. The forms were characterized and studied by thermal analysis, X-ray powder diffraction, scanning electron microscopy, and solubility testing. Six polymorphic forms of rifaximin, designated I-VI, were obtained by the crystallization process by evaporation of the solvent. Some polymorphic forms obtained in this work may not have the same excellent tolerability as the reference medicine; therefore, studies such as these are extremely important and point to the need for greater requirements by the regulatory agencies overseeing polymorph analysis of the raw materials used in the manufacture of medicines marketed globally. These analyses are not required in the majority of official compendia. Partnerships among industries, research centers, and universities would be a viable way to consolidate research in this area and contribute to improving the quality of solid drugs.
Topics: Anti-Infective Agents; Calorimetry, Differential Scanning; Crystallization; Microscopy, Electron, Scanning; Particle Size; Powder Diffraction; Rifamycins; Rifaximin; Solubility; Thermogravimetry
PubMed: 27455934
DOI: 10.5740/jaoacint.16-0053