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Quantification analysis with near-infrared (NIR) spectroscopy typically requires utilizing chemometric techniques, such as partial least squares (PLS) method, to achieve the desired selectivity. This article points out a major limitation of these statistical-based calibration methods. The limitation is that the techniques suffer from the potential for chance correlation. In this article, the impact of chance correlation on the robustness of PLS model was illustrated via a pharmaceutical application with NIR to the content uniformity determination of tablets. The procedure involves evaluating the PLS models generated with two sets of calibration tablets incorporated with distinct degree of concentration correlation between the active pharmaceutical ingredient (API) and excipients. The selectivity and robustness of the two models were examined by using a series of data sets associated with placebo tablets and tablets incorporated with variations from excipient content, hardness and particle size. The result clearly revealed that the strong correlation observed in the PLS model created by the correlated design was not solely based on the API information, and there was an intrinsic difference in the variances described by the two calibration models. Diagnostic tools that enable the characterization of the chemical selectivity of the calibration model were also proposed for pharmaceutical quantitative analysis. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1155–1166, 2009 [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powders measured by the ASTM D 6940-04 segregation tester using design of experiments (DOE) approaches. The test blends consisted of 4% aspirin (ASP) and 96% microcrystalline cellulose (MCC) with and without magnesium stearate (MgS). The segregation tendency of a blend was determined by measuring the last/first (L/F) ratio, the ratio of aspirin concentrations between the first and last samples discharged from the tester. A 22 factorial design was used to determine the effects of measurement parameters [amount of material loaded (W), number of segregation cycles] with number of replicates 6. ANOVA showed that W was a critical parameter for segregation testing. The L/F value deviated further from 1 (greater segregation tendency) with increasing W. A 23 full factorial design was used to assess the effects of formulation variables: grade of ASP (unmilled, milled), grade of MCC, and amount of lubricant, MgS. MLR and ANOVA showed that the grade of ASP was the main effect contributing to segregation tendency. Principal Component Regression Analysis established a correlation between L/F and the physical properties of the blend related to ASP and MCC, the ASP/MCC particle size ratio (PSR) and powder cohesion. The physical properties of the blend related to density and flow were not influenced by the grade of ASP and were not related to the segregation tendency of the blend. The direct relationship between L/F and PSR was determined by univariate analysis. Segregation tendency increased as the ASP to MCC particle size increased. This study highlighted critical test parameters for segregation testing and identified critical physical properties of the blends that influence segregation tendency. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4485–4497, 2008 [ABSTRACT FROM AUTHOR]

• Molecular structure of 6-methyl-2-aminopyridine based co-crystal. • Efficient and catalyst free method for synthesis of porous carbon. • The specific capacitance of 44.69 f/g at sweep rate 2mv/s. • 83.88% specific capacitance retention after 1900 cycles. Supercapacitors or ultra-capacitors are well thought-out best approach to fulfil the indispensable requirements of energy storage. Supercapacitive electrode materials have become interest of scientists. In the present study, we have reported an efficient and catalyst free method for synthesis of porous carbon by the pyrolysis of salt, prepared by reaction of organic acid with organic base for supercapacitive application. The prepared salt was characterized by single crystal analysis, 1H NMR, single crystal XRD and FT-IR. The salt derived porous carbon material was then characterized by powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The specific surface area of porous carbon was calculated by BET analysis found to be 347 m2/g. Electrode material showed good capacitive response. The specific capacitance of sample was Ca. 44.69 F/g at sweep rate 2 mV/s and retains 83.88% of its initial capacitance after 1900 cycles. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Design and synthesis of fluorinated chalcones. • Investigation of DNA binding capability of chalcones. • Chalcones as moderate Urease inhibitor. • Docking studies agrees well with experimental data. • NBO, FMO and NPA analysis through DFT. Two new chalcones namely 3-(3-Bromo-phenyl)-1-(2-trifluoromethyl-phenyl)-propenone (1) and 3-(3-Bromo-5-chloro-phenyl)-1-(2-trifluoromethyl-phenyl)-propenone (2) were synthesized from substituted aldehydes and fluorinated acetophenone through base catalyzed condensation reaction. The structural confirmation of synthesized compounds was furnished by different spectroscopic techniques i.e., (1H NMR, FT-IR, mass spectrometry and UV–visible analysis). The interaction of 1 and 2 with Salmon sperm DNA (SS-DNA) was studied using UV–visible spectroscopy. The Urease inhibition and antioxidant potential were also evaluated experimentally which were further supported by molecular docking studies. To investigate drug discovery endeavors of our synthesized compounds ADME properties were explored. The calculations of frontier molecular orbitals (FMOs), natural population analysis (NPA), natural bond orbitals (NBOs) and nonlinear optical (NLO) analysis of 1 and 2 were performed at B3LYP/6-311 G(d,p) level of DFT. Time dependent density functional theory (TD-DFT) was used to describe photo-physical properties of synthesized compounds. Additionally, natural population analysis (NPA) and NBO were used to explore inter and intra molecular interactions as well as hyper conjugative interactions. The experimental results revealed that the compounds 1 and 2 interact strongly with SS-DNA through intercalation mode. UV/Vis spectrum obtained from DFT calculations correlates very well with the experimentally obtained spectrum. Furthermore, DFT studies showed that hyper conjugative interactions lead to higher stabilization of 2 than 1. [ABSTRACT FROM AUTHOR]

In this work, we reported the synthesis of hydrazide derivatives namely; N' -(4-(prop-2-ynyloxy)benzylidene)isonicotinohydrazide (1) and 4-methyl- N '-(4(prop-2-ynyloxy)benzylidene)- benzenesulfonohydrazide (2), their characterization through spectroscopic techniques as EIMS, 1H NMR, FT-IR, UV–Visible and single crystal X-ray diffraction (SC-XRD). Quantum chemical methods were performed for both compounds (1) and (2) to explore the structural, spectral and electronic properties for comparative analysis with experimental data. The theoretical vibrational spectra (FT-IR), frontier molecular orbitals (FMOs) and nonlinear optical (NLO) analysis were performed at DFT/B3LYP/6-311 + G(d,p) level. Natural bond orbitals (NBOs) analysis was carried out at M06-2X/6-311G(d,p)level of theory. However, the time dependent density functional theory (TDDFT) was used for the calculations of vertical electronic transition states at B3LYP level with 6-311 + G(d,p) basis set. The NBO analysis revealed that both compounds (1) and (2) have high molecular stability due to hyperconjugative interactions. Moreover, the global reactivity descriptors were calculated using the energies of FMOs. NLO analysis showed that both compounds (1) and (2) have significant NLO properties as compared to prototype compound (urea) which disclosed their potential for technology related applications. Overall, a well synchroneity is found between the experimental dataand DFT based results of both compounds. Image 1 • Two novel hydrazide derivatives were synthesized. • XRD, 1H NMR, FT-IR and UV–Vis were performed for the characterization. • Computational study was done for comparative analysis. • Comparative study reveals a good agreement between experimental and DFT results. • FMOs, NBO analysis and nonlinear optical (NLO) properties were calculated. [ABSTRACT FROM AUTHOR]

In the current work, organic cyclopenta-thiophene (CPT) based derivatives (FICR and FICD1-FICD5) were designed by the modulation of end-capped acceptor group of the reference molecule i.e., FICR, to explore their nonlinear optical (NLO) response. The effect of terminal acceptor and donor groups in the tailored compounds was explored by using DFT based quantum calculations. The UV-Vis analysis, frontier molecular orbitals (FMOs), transition density matrix (TDM), natural bond orbitals (NBOs), density of states (DOS), nonlinear optical (NLO) analyses were performed at M06/6-311G(d,p) functional. The LUMO-HOMO band gaps of FICD1-FICD5 were found to be smaller (1.75-1.92 eV) comparative to FICR (1.98 eV). Moreover, the global reactivity parameters (GRPs) were correlated with the results of other analyses. FICD2 and FICD5 with lowest band gap 1.73 and 1.75 eV showed less hardness (0.86 and 0.87 eV, respectively), high softness (0.58 and 0.57 eV -1 ), and larger absorption spectrum (815 and 813 nm) in gaseous phase and (889 and 880 nm) in solvent phase among all entitled compounds. All the designed chromophores (FICD1-FICD5) demonstrated a significant NLO response as compared to FICR. Particularly, FICD2 and FICD5 exhibited the highest average linear polarizability (<α>) [2.86 × 10 -22 and 2.88 × 10 -22 esu], first hyperpolarizability (β tot ) (8.43 × 10 -27 and 8.35 × 10 -27 esu) and second hyperpolarizability (γ tot ) (13.20 × 10 -32 and 13.0 × 10 -32 esu) values as compared to the other derivatives. In nutshell, structural modeling of CPT based chromophores with extended acceptors, can be significantly utilized to achieve potential NLO materials., (© 2024. The Author(s).)

Polysaccharides are favourable and promising biopolymers for wound care applications due to their abundant natural availability, low cost and excellent biocompatibility. They possess different functional groups, such as carboxylic, hydroxyl and amino, and can easily be modified to obtain the desirable properties and various forms. This review systematically analyses the recent progress in polysaccharides derived materials for wound care applications, emphasizing the most commonly used cellulose, chitosan, alginate, starch, dextran and hyaluronic acid derived materials. The distinctive attributes of each polysaccharide derived wound care material are discussed in detail, along with their different forms, i.e., films, membranes, sponges, nanoemulsions, nanofibers, scaffolds, nanocomposites and hydrogels. The processing methods to develop polysaccharides derived wound care materials are also summarized. In the end, challenges related to polysaccharides derived materials in wound care management are listed, and suggestions are given to expand their utilization in the future to compete with conventional wound healing materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to excellent biocompatibility, bioactivities, and osteoconductivity, hydroxyapatite (HAp) is considered as one of the most suitable biomaterials for numerous biomedical applications. Herein, HAp was fabricated using a bottom-up approach, i.e., a wet chemical method, and its composites with TiC, h-BN, and ZrO 2 were fabricated by a solid-state reaction method with enhanced mechanical and biological performances. Structural, surface morphology, and mechanical behavior of the fabricated composites were characterized using various characterization techniques. Furthermore, transmission electron microscopy study revealed a randomly oriented rod-like morphology, with the length and width of these nanorods ranging from 78 to 122 and from 9 to 13 nm. Moreover, the mechanical characterizations of the composite HZBT4 (80HAp-10TiC-5h-BN-5ZrO 2 ) reveal a very high compressive strength (246 MPa), which is comparable to that of the steel (250 MPa), fracture toughness (14.78 MPa m 1/2 ), and Young's modulus (1.02 GPa). In order to check the biocompatibility of the composites, numerous biological tests were also performed on different body organs of healthy adult Sprague-Dawley rats. This study suggests that the composite HZBT4 could not reveal any significant influence on the hematological, serum biochemical, and histopathological parameters. Hence, the fabricated composite can be used for several biological applications, such as bone implants, bone grafting, and bone regeneration.

Owing to the broad applications of quaternary ammonium salts (QAS), we present the synthesis of benzimidazolium-based analogues with variation in the alkyl and alkoxy group at N-1 and N-3 positions. All the compounds were characterized by spectroscopic techniques and found stable to air and moisture both in the solid and solution state. Moreover, molecular structures were established through single-crystal X-ray diffraction studies. The crystal packing of the compounds was stabilized by numerous intermolecular interactions explored by Hirshfeld surface analysis. The enrichment ratio was calculated for the pairs of chemical species to acquire the highest propensity to form contacts. Void analysis was carried out to check the mechanical response of the compounds. Furthermore, theoretical investigations were also performed to explore the optoelectronic properties of compounds. Natural population analysis (NPA) has been conducted to evaluate the distribution of charges on the synthesized compounds, whereas high band gaps of the synthesized compounds by frontier molecular orbital (FMO) analysis indicated their stability. Nonlinear optical (NLO) analysis revealed that the synthesized QAS demonstrates significantly improved NLO behaviour than the standard urea., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

In this work, four fluorinated α, β-unsaturated ketones named as 3-(3-bromophenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (1), 3-(4-methoxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (2), 3-(3-bromo-5-chloro-2-hydroxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (3) and 3-(2-hydroxy-5-methylphenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (4) were synthesized by Claisen-Schmidt reaction. The synthesized molecules were then characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR), 1 H-NMR, 13 C-NMR, and mass spectrometry. The antioxidant potential, Urease inhibition, and interaction of compounds 1-4 with Salmon sperm DNA were experimentally explored and supported by molecular docking studies. The synthesized compounds strongly interact with SS-DNA through intercalative mode. It was noticed that compound 1 served as potent Urease inhibitor while compound 4 as better antioxidant among synthesized compounds. Moreover, frontier molecular orbitals, nonlinear optical (NLO) properties, natural bond orbitals, molecular electrostatic potential, natural population analysis, and photophysical properties of synthesized compounds were accomplished through density functional theory and time-dependent density functional theory. The band gap of all the compounds have been worked out using Taucs method. In addition to that, a precise comparative account of UV and IR data obtained from theoretical and experimental findings showed good agreement between theoretical and experimental data. The findings of our studies reflected that compounds 1-4 possess better NLO properties than Urea standard and the band gap data also reflected their prospective use towards optoelectronic materials. The better NLO behavior of compounds was attributed to the noncentrosymmetric structure of synthesized compounds., (© 2023 Wiley Periodicals LLC.)

Hydrogen is currently considered as the best alternative for traditional fuels due to its sustainable and ecofriendly nature. Additionally, hydrogen dissociation is a critical step in almost all hydrogenation reactions, which is crucial in industrial chemical production. A cost-effective and efficient catalyst with favorable activity for this step is highly desirable. Herein, transition-metal-doped fullerene (TM@C 60 ) complexes are designed and investigated as single-atom catalysts for the hydrogen splitting process. Interaction energy analysis ( E int ) is also carried out to demonstrate the stability of designed TM@C 60 metallofullerenes, which reveals that all the designed complexes have higher thermodynamic stability. Furthermore, among all the studied metallofullerenes, the best catalytic efficiency for hydrogen dissociation is seen for the Sc@C 60 catalyst E a = 0.13 eV followed by the V@C 60 catalyst E a = 0.19 eV. The hydrogen activation and dissociation processes over TM@C 60 metallofullerenes is further elaborated by analyzing charge transfer via the natural bond orbital and electron density difference analyses. Additionally, quantum theory of atoms in molecule analysis is carried out to investigate the nature of interatomic interactions between hydrogen molecules and TMs@C 60 metallofullerenes. Overall, results of the current study declare that the Sc@C 60 catalyst can act as a low cost, highly efficient, and noble metal-free single-atom catalyst to efficiently catalyze hydrogen dissociation reaction., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Herein, present study mainly focuses on the synthesis and characterizations of boron nitride reinforced waste zirconia (wZrO 2 ) with different concentrations. Composites were prepared via a scalable solid-state reaction method. Various physical parameters such as density, ionic concentration, polaron radius, and field strength were evaluated. XRD results reveal crystalline nature with a major phase of tetragonal zirconia and as boron nitride is reinforced, the tetragonal transforms into a monoclinic zirconia. Interconnected spherical grains and nanosheets were observed using FESEM. Mechanical characterizations revealed the highest compressive strength of 266 MPa. The latent fingerprints were visualized using a composite on different surfaces, implementing the powder dusting and solution techniques. MTT assay was performed and revealed good biocompatible nature. These results reveal that composite is suitable for fabrication of bioceramics with acceptable mechanical and biological performances. The composite can also be utilized for latent fingerprint detection in forensic science., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in the present paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Y-series-based non-fullerene acceptors (NFAs) have achieved significant deliberation by chemists and physicists because the promising optical and photochemical properties associated with high-performance OSCs can be further tuned through end-capped modification. In this work, such modifications of Y-series benzothiadiazole-based NFAs were accomplished theoretically to propose new acceptors for photovoltaic cells (PVCs). The recently synthesized Y-series non-fullerene acceptor m-BTP-PhC6 was taken as a reference acceptor. We designed five new acceptors (BTP1-BTP5) through the structural modification at both ends of acceptor groups and evaluated their performance by applying DFT and TD-DFT. The newly engineered molecules exhibited a narrower bandgap (E g ) than the reference (R) resulting in better intramolecular charge transfer (ICT). Further, the designed acceptors expressed the maximum absorption in the region of 600-800 nm revealing a redshift in their absorption spectrum. Low excitation energy and low exciton binding energy were noted for designed acceptors confirming them as better candidates for high PCE of solar cells. Low reorganizational energy for the mobility of holes and electrons was also observed for the designed molecules, indicating improved charge transfer properties. The newly tailored acceptor BTP4 was found to be the promising candidate among all acceptors because of lower bandgap, lower exciton binding energy, reorganizational energy, and redshift of the absorption spectrum. The complex analysis of BTP4 with donor polymer PTB7-Th and PM6 was executed at the same DFT level. Furthermore, FMOs studies showed relatively rich electron density in the acceptor groups of LUMO as compared to the reference molecule. The overall theoretical results of this study showed that the designed acceptors played a productive and effective role in uplifting the efficiency of fullerene-free energy devices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The performance of organic solar cells (OSCs) has been improving steadily over the last few years, owing to the optimization of device fabrication, fine-tuning of morphology, and thin-film processing. Thiophene core containing fused ring-type non-fullerene acceptors (NFAs) achieved significant proficiency for highly efficient OSCs. Quantum chemical computations are utilized herein with the motive of suggesting new NIR sensitive, highly efficient low-band gap materials for OSCs. A series of extended conjugated A-π-D-π-A architectured novel fused-ring NFAs (FUIC-1-FUIC-6) containing thieno[2,3- b ]thiophene-based donor core are proposed by substituting the end-capped units of synthesized molecule F10IC. Different properties including frontier molecular orbital analysis, density of states analysis, transition density matrix analysis, excitation energy, reorganizational energies of both holes (λ h ) and electrons (λ e ), and open-circuit voltage ( V oc ) were performed employing the density functional theory approach. Charge transfer analysis of the best-designed molecule with the donor complex was analyzed to comprehend the efficiency of novel constructed molecules (FUIC-1-FUIC-6) and compared with the reference. End-caped acceptor alteration induces the reduction of the energy gap between HOMO-LUMO (1.88 eV), tunes the energy levels, longer absorption in the visible and near-infrared regions, larger V oc , smaller reorganizational energies, and binding energy values in designed structures (FUIC-1-FUIC-6) in comparison to reference (FUIC). The designed molecules show the best agreement with the PTBT-T donor polymer blend and cause the highest charge from the HOMO to the LUMO orbital. Our findings predicted that thieno[2,3- b ] thiophene-based newly designed molecules would be efficient NFAs with outstanding photovoltaic characteristics and can be used in future applications of OSCs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Propolis (bee glue) is a complex, phyto-based resinous material obtained from beehives. Its chemical and biological properties vary with respect to bee species, type of plants, geographical location, and climate of a particular area. This study was planned with the aim of determining the chemical composition and to investigate various properties (against oxidants and microbes) of different extracts of Saudi propolis collected from Arabian honey bee ( Apis mellifera jemenitica ) colonies headed by young queens. Chemical analysis of propolis extracts with different solvents, i.e., ethyl acetate (Eac), methanol (Met), butanol (BuT), and hexane (Hex) was done through colorimetry for the total phenolic content (TPC) and total flavonoid content (TFC) evaluation. For separation and extensive characterization of the Met extract, chromatography and 1 H NMR were deployed. Six different microorganisms were selected to analyze the Saudi-propolis-based extract's antimicrobial nature by measuring zones of inhibition (ZOI) and minimum inhibitory concentration (MIC). Molecular docking was done by utilizing AutodDock, and sketching of ligands was performed through Marvin Chem Sketch (MCS), and the resultant data after 2D and 3D clean were stored in .mol format. The highest TFC (96.65 mg quercetin equivalents (QE)/g of propolis) and TPC (325 mg gallic acid equivalents (GAE)/g of propolis) were noted for Met. Six familiar compounds were isolated, and recognition was done with NMR. Met extract showed the greatest 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) free radical scavenging activity and Ferric Reducing Antioxidant Power (FRAP). Met showed max microbial activity against Staphylococcus aureus (ZOI = 18.67 mm, MIC = 0.625 mg/mL), whereas the minimum was observed in Hex against E. coli (ZOI = 6.33 mm, MIC = 2.50 mg/mL). Furthermore, the molecular docking process established the biological activity of separated compounds against HCK (Hematopoietic cell kinase) and Gyrase B of S. aureus . Moreover, the stability of protein-ligand complexes was further established through molecular dynamic simulation studies, which showed that the receptor-ligand complexes were quite stable. Results of this research will pave the way for further consolidated analysis of propolis obtained from Arabian honey bees ( A. m. jemenitica ).

End-capped modification is an efficient approach for enhancing the power conversion efficiency of organic solar cells (OSCs). Herein, five novel acceptor molecules have been designed by end-capper modification of the recently synthesized molecule NTIC ( R ). Different geometric and photovoltaic properties like frontier molecular orbital analysis, absorption maximum, transition density matrix analysis, reorganizational energy, binding energy, oscillator strength, energy of excitation, and charge transfer analysis of designed and reference molecules have been computed by employing density functional theory and time-dependent density functional theory. Designed molecules expressed a narrow energy band gap ( E g ) with red-shifting in the absorption spectrum. Additionally, low excitation and binding energies are also noted in designed molecules. Excellent values of hole and electron reorganizational energies suggested that designed molecules are effective contributors to the development of the active layer of the organic solar cells. Further, a complex study is also performed for evaluation of charge transfer between the acceptor molecule and the donor polymer. Results of all analyses recommended that designed molecules are effective candidates for high-performance organic solar cell applications., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

In this study, six compositions in the system [ x (h-BN)-(100 - x )ZrO 2 ] (10 ≤ x ≤ 90) were synthesized by a bottom up approach, i.e. , the solid-state reaction technique. XRD results showed the formation of a novel and main phase of zirconium oxynitrate ZrO(NO 3 ) 2 and SEM exhibited mixed morphology of layered and stacked h-BN nanosheets with ZrO 2 grains. The composite sample 10 wt% h-BN + 90 wt% ZrO 2 (10B90Z) showed outstanding mechanical properties for different parameters, i.e. , density (3.12 g cm -3 ), Young's modulus (10.10 GPa), toughness (2.56 MJ m -3 ), and maximum mechanical strength (227.33 MPa). The current study further checked the in vivo toxicity of composite 10B90Z and composite 90B10Z using Drosophila melanogaster . The composite 10B90Z showed less cytotoxicity in this model, while the composite 90B10Z showed higher toxicity in terms of organ development as well as internal damage of the gut mostly at the lower concentrations of 1, 10, and 25 μg mL -1 . Altogether, the current study proposes the composite 10B90Z as an ideal compound for applications in biomedical research. This composite 10B90Z displays remarkable mechanical and biological performances, due to which we recommend this composition for various biomedical applications., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Facilitating utility of prior knowledge to accelerate evidence-based new drug development is a focus of several communities of knowledge, such as clinical pharmacology. For example, progress has been made via modeling and simulation of pharmacokinetic and pharmacodynamic relationships in the more effective use of "End of Phase 2" regulatory meetings for a New Drug Application (NDA). Facilitating utility of prior "Chemistry, Manufacturing, and Controls" (CMC) knowledge to accelerate new drug development and regulatory review process is also a topic of significant interest. This paper focuses on facilitating the utility of prior pharmaceutical formulation knowledge to accelerate drug product development and regulatory review of generic and biosimilar products. This knowledge is described as New Prior Knowledge (NPK) because research is often needed to fill ontological (i.e., the domain of connectivity between concepts and phenomena), epistemological (i.e., distinguishing knowledge or justified belief from the opinion), and methodological gaps in information derived a decade or so ago. The corporate economic advantages of such knowledge are derived, in part, when significant portions remain a trade secret. The proposed NPK seeks to generate knowledge about critical aspects of pharmaceutical quality and failure modes to place it in the public domain and to facilitate accelerated and more confident development and regulatory review of generic products. The paradoxical combination of "new" and "prior knowledge" is chosen deliberately to highlight both a distinction from proprietary and trade secret information and to acknowledge certain historical dogmas inherent in the current practices. Considerations for operationalizing NPK are also summarized.

Levothyroxine sodium pentahydrate (LEVO) tablets have been on the US market since the mid-twentieth century and remain the most highly prescribed product. Unfortunately, levothyroxine sodium tablets have also been one of the most highly recalled products due to potency and dissolution failures on stability. In 2008, the assay limits were tightened, yet the recalls did not decline, which highlights the serious quality concerns remaining to be elucidated. The aim of the present investigation was to test the hypothesis that the solid-state physical instability of LEVO precedes the chemical instability leading to product failure. The failure mode was hypothesized to be the dehydration of the crystal hydrate, when exposed to certain humidity and temperature conditions, followed by the oxidation of the API through vacated channels. It was previously reported by the authors that LEVO degradation occurred in the presence of oxygen at a low relative humidity (RH). Furthermore, powder X-ray diffractometry shows changes in the crystal lattice of LEVO initially and through the dehydration stages. Storage of LEVO at RT and 40 °C at 4-6% RH for 12 days shows a decrease in d-spacing of the (00 l) planes. Based on a structure solution from the powder data of the dehydrated material, the basic packing motif persists to varying degrees even when fully dehydrated along with disordering. Therefore, the crystal structure changes of LEVO depend on RH and temperature and are now explicable at the structural level for the first time. This exemplifies the dire need for "new prior knowledge" in generic product development.

Hispidulin is well-known natural bioactive flavone on behalf of its pharmacological aspects. This review contains data on isolation, synthetic methodology, pharmacokinetics and bioactivities of hispidulin. The article provides a critical assessment of present knowledge about hispidulin with some clear conclusions, perspectives and directions for future research in potential applications.

Hispidulin is well-known natural bioactive flavone on behalf of its pharmacological aspects. This review contains data on isolation, synthetic methodology, pharmacokinetics and bioactivities of hispidulin. The article provides a critical assessment of present knowledge about hispidulin with some clear conclusions, perspectives and directions for future research in potential applications.

In the title compound, C(16)H(13)BrFN(3)O(2)S, the dihedral angle between the aromatic rings is 2.55 (19)° and the C=N-N=C torsion angle is 178.9 (3)°. The conformation of the thia-zine ring is an envelope, with the S atom displaced by -0.811 (3) Å from the mean plane of the other five atoms (r.m.s. deviation = 0.042 Å). In the crystal, C-H⋯O inter-actions link the mol-ecules and weak aromatic π-π stacking between the fluoro-benzene and bromo-benzene rings [centroid-centroid separation = 3.720 (2) Å and inter-planar angle = 2.6 (2)°] is also observed.

In the title compound, [Cu(C(12)H(18)N(2)O(2))]·0.25H(2)O, the coordination of the O,N,N',O'-tetra-dentate ligand results in a cis-CuN(2)O(2) square-planar geometry for the metal ion and the presence of two six-membered and one five-membered chelate rings. The complete complex mol-ecule is close to planar (r.m.s. deviation = 0.047 Å). The uncoordinated water mol-ecule (O-atom site symmetry 2) was modelled as half occupied. In the crystal, C-H⋯O(w) and O(w)-H⋯O (w = water) hydrogen bonds link the components into layers parallel to ab plane.

The purpose of this study is to provisionally classify, based on the Biopharmaceutics Classification System (BCS), drugs in immediate-release dosage forms that appear on the World Health Organization (WHO) Essential Drug List. The classification in this report is based on the aqueous solubility of the drugs reported in commonly available reference literature and a correlation of human intestinal membrane permeability for a set of 29 reference drugs with their calculated partition coefficients. The WHO Essential Drug List consists of a total of 325 medicines and 260 drugs, of which 123 are oral drugs in immediate-release (IR) products. Drugs with dose numbers less than or equal to unity [Do = (maximum dose strength/250 mL)/solubility < or = 1] are defined as high-solubility drugs. Drug solubility for the uncharged, lowest-solubility form reported in the Merck Index or USP was used. Of the 123 WHO oral drugs in immediate-release dosage forms, 67% (82) were determined to be high-solubility drugs. The classification of permeability is based on correlations of human intestinal permeability of 29 reference drugs with the estimated log P or CLogP lipophilicity values. Metoprolol was chosen as the reference compound for permeability and log P or CLogP. Log P and CLogP were linearly correlated (r2 = 0.78) for 104 drugs. A total of 53 (43.1%) and 62 (50.4%) drugs on the WHO list exhibited log P and CLogP estimates, respectively, that were greater than or equal to the corresponding metoprolol value and are classified as high-permeability drugs. The percentages of the drugs in immediate-release dosage forms that were classified as BCS Class 1, Class 2, Class 3, and Class 4 drugs using dose number and log Pwere as follows: 23.6% in Class 1, 17.1% in Class 2, 31.7% in Class 3, and 10.6% in Class 4. The remaining 17.1% of the drugs could not be classified because of the inability to calculate log P values because of missing fragments. The corresponding percentages in the various BCS classes with dose number and CLogP criteria were similar: 28.5% in Class 1, 19.5% in Class 2, 35.0% in Class 3, and 9.8% in Class 4. The remaining 7.3% of the drugs could not be classified since CLogP could not be calculated. These results suggest that a satisfactory bioequivalence (BE) test for more than 55% of the high-solubility Class 1 and Class 3 drug products on the WHO Essential Drug List may be based on an in vitro dissolution test. The use of more easily implemented, routinely monitored, and reliable in vitro dissolution tests can ensure the clinical performance of drug products that appear on the WHO Essential Medicines List.