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1.
Cureus ; 15(6): e40716, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37485208

RESUMO

Background Endotracheal intubation in the intensive care unit (ICU) is often a risky procedure due to the emergency situation, unstable condition of the patient, and technical problems such as inadequate positioning. Several new techniques, such as video laryngoscopy, have been developed recently to improve the success rate of first-pass intubations and reduce complications. We conducted this study to compare a non-channeled reusable video laryngoscope BPL VL-02 (manufactured by BPL Medical Technologies, Bangalore, India) with a conventional laryngoscope for intubation of adult patients in the ICU. Methodology A total of 72 ICU patients were randomly allocated to be intubated with either conventional direct laryngoscopy via Macintosh blade (group A) or video laryngoscopy with BPL VL-02 (group B). All patients were intubated by the primary investigator and the assistant noted the following parameters: the total number of intubation attempts, total duration of intubation, assistance or alternative technique required, Cormack Lehane grading, and any complications. Results There was no significant difference in the Cormack Lehane grading, number of attempts, or complications between the two groups. On comparing the assistance required during intubation in patients, it was observed that four (11.11%) patients in group A and seven (19.44%) patients in group B needed backward, upward, and rightward pressure on the larynx assistance during intubation. In five (13.89%) patients in group B, Stylet was required during intubation. The difference was statistically significant (p = 0.0308). The video laryngoscopy group (group B) had a longer mean duration of intubation (64.36 ± 6.28 seconds) compared to group A (45.72 ± 11.45 seconds), and the difference was statistically significant (p < 0.0001). Conclusions Non-channeled video laryngoscope (BPL VL-02) is not a suitable alternative to conventional direct laryngoscopy with a Macintosh blade in terms of successful first-pass intubation, total duration of intubation, and assistance required.

2.
Mol Pharm ; 20(4): 2266-2275, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36929729

RESUMO

The purpose of the present study was to evaluate whether the population balance model (PBM) could be a suitable model for the precipitation of weak base and zwitterionic drugs in the gastrointestinal pH environment. Five poorly soluble drugs were used as model drugs (dipyridamole, haloperidol, papaverine, phenazopyridine, and tosufloxacin). PBM consists of the equations for primary nucleation, secondary nucleation, and particle growth. Each equation has two empirical parameters. The pH shift (pH-dumping) precipitation test (pH 3.0 to 6.5) was used to determine the model parameters for each drug. It was difficult to determine all six parameters by simultaneously fitting them to the precipitation profiles. Therefore, the number of model parameters was reduced from six to three by neglecting the secondary nucleation process and applying a common exponent number for the particle growth equation. Despite reducing the parameter number, PBM appropriately described the precipitation profiles in the pH shift tests. The constructed PBM model was then used to predict the precipitation profiles in an artificial stomach-intestine transfer (ASIT) test. PBM appropriately predicted the precipitation profiles in the ASIT test. These results suggested that PBM can be a suitable model to represent the precipitation of weak base and zwitterionic drugs in the gastrointestinal pH environment for biopharmaceutics modeling and simulation.


Assuntos
Trato Gastrointestinal , Estômago , Solubilidade , Administração Oral , Simulação por Computador , Concentração de Íons de Hidrogênio , Modelos Biológicos , Precipitação Química , Absorção Intestinal
3.
Adv Exp Med Biol ; 1394: 103-117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587384

RESUMO

This chapter focuses on the division and location of brain deformities such as tumors in magnetic resonance imaging (MRI) through Chan-Vese active contour segmentation. Brain tumor division and identification is a major test in the area of biomedical picture processing. To detect the size and location of the tumor, various techniques are available, but active contour gives accurate knowledge of the region for segmentation. Chan-Vese Active contour method provides independent, robust and more flexible segmentation. In this chapter, firstly we used preprocessing technique in which noise and unused parts of the brain and skull are removed, for this we proposed the skull stripping method. Then, we applied feature extraction to enhance the image intensity and quality, and lastly, used Chan-Vese active contour with a level set image segmentation technique to detect the tumor. The tumor area was calculated after tumor detection.


Assuntos
Neoplasias Encefálicas , Neoplasias da Medula Espinal , Humanos , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Carcinogênese , Transformação Celular Neoplásica , Neoplasias da Medula Espinal/diagnóstico por imagem , Biologia Computacional , Algoritmos , Processamento de Imagem Assistida por Computador/métodos
4.
Artigo em Inglês | MEDLINE | ID: mdl-36512547

RESUMO

For the simultaneous identification and quantification of five nitrofurans metabolites in farmed shrimp and fish, 3-amino-2-oxazolidinone (AOZ), 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), 1-aminohydantoine (AHD), semicarbazide (SEM), and 3,5-dinitrosalicylic acid hydrazide (DNSH), an accurate, precise, and specific method was developed. The mixture of water and methanol (60/40; v/v) was found to be the final optimised solvent for injection. The analytical run duration was 7 min, and the mobile phase included 2 mM methanol and ammonium formate. The new reference point for action (RPA) of 0.50 µg kg-1 as per EC/1871/2019 was taken into consideration and evaluated for the performance characteristics as per the CIR (EC)/2021/808 criteria. Specificity, relative retention time (≤0.25%) relative ion ratio (≤40%), linearity (0.25 to 2.0 µg kg-1), trueness (between 82.8 and 118.1%), repeatability (RSDr ≤14%), within lab reproducibility (RSDwr ≤16.9%), CCα (0.32-0.36 µg kg-1), ruggedness and relative matrix effect (≤14.26%) achieved acceptable values.


Assuntos
Nitrofuranos , Espectrometria de Massas em Tandem , Animais , Crustáceos/química , Crustáceos/metabolismo , Peixes/metabolismo , Metanol , Nitrofuranos/química , Nitrofuranos/metabolismo , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
5.
Int J Pharm ; 623: 121908, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35700869

RESUMO

Multiparticulate formulations allow for the design of specialized pharmaceutical dosage forms that cater to the needs of a wide range of patient demographics, such as pediatric and geriatric populations, by affording control over the release rate and facilitating the formulation of fixed-dose combination drugs. Melt spray-congealing (MSC) is a method for preparing multiparticulate dosage forms from a suspension or solid solution of active pharamaceutical ingredients (API) and a molten carrier matrix. Stearyl alcohol and poloxamer 407 mixtures are widely used as carrier matrices in MSC microsphere formulations. In this report, the phase equilibria of stearyl alcohol-poloxamer 407 mixtures were investigated by generating binary phase diagrams of composition, i.e. weight/weight percent of poloxamer 407 in stearyl alcohol, and temperature in the molten form and the solid state. The phase equilibria of the molten state were characterized by 1H NMR measurements. The miscibility curves of stearyl alcohol-poloxamer 407 molten mixtures revealed that stearyl alcohol and poloxamer 407 are not miscible in all proportions and that miscibility substantially increases with temperature. The phase equilibria of the solid state were characterized by DSC and PXRD experiments. The phase diagrams of the solid state indicate that stearyl alcohol and poloxamer 407 crystallize and melt separately and, thus, do not form a eutectic or a single phase. The phases equilibria of the bulk mixtures were compared to the phases observed in placebo MSC microspheres and it was determined that the microspheres consist of a mixture of thermodynamically stable and metastable stearyl alcohol crystals immediately after manufacture.


Assuntos
Álcoois Graxos , Poloxâmero , Idoso , Criança , Excipientes , Humanos , Poloxâmero/química , Solubilidade
6.
Adv Mater ; 33(49): e2105004, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34626028

RESUMO

Dynamic control of structural colors across the visible spectrum with high brightness has proven to be a difficult challenge. Here, this is addressed with a tuneable reflective nano-optical cavity that uses an electroactive conducting polymer (poly(thieno[3,4-b]thiophene)) as spacer layer. Electrochemical doping and dedoping of the polymer spacer layer provides reversible tuning of the cavity's structural color throughout the entire visible range and beyond. Furthermore, the cavity provides high peak reflectance that varies only slightly between the reduced and oxidized states of the polymer. The results indicate that the polymer undergoes large reversible thickness changes upon redox tuning, aided by changes in optical properties and low visible absorption. The electroactive cavity concept may find particular use in reflective displays, by opening for tuneable monopixels that eliminate limitations in brightness of traditional subpixel-based systems.

7.
Adv Mater ; 33(33): e2102451, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34219300

RESUMO

Precise manipulation of light-matter interactions has enabled a wide variety of approaches to create bright and vivid structural colors. Techniques utilizing photonic crystals, Fabry-Pérot cavities, plasmonics, or high-refractive-index dielectric metasurfaces have been studied for applications ranging from optical coatings to reflective displays. However, complicated fabrication procedures for sub-wavelength nanostructures, limited active areas, and inherent absence of tunability of these approaches impede their further development toward flexible, large-scale, and switchable devices compatible with facile and cost-effective production. Here, a novel method is presented to generate structural color images based on monochromic conducting polymer films prepared on metallic surfaces via vapor phase polymerization and ultraviolet (UV) light patterning. Varying the UV dose enables synergistic control of both nanoscale film thickness and polymer permittivity, which generates controllable structural colors from violet to red. Together with grayscale photomasks this enables facile fabrication of high-resolution structural color images. Dynamic tuning of colored surfaces and images via electrochemical modulation of the polymer redox state is further demonstrated. The simple structure, facile fabrication, wide color gamut, and dynamic color tuning make this concept competitive for applications like multifunctional displays.

8.
Adv Mater ; 33(36): e2101519, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34313346

RESUMO

Cellulose nanocrystals (CNCs) possess the ability to form helical periodic structures that generate structural colors. Due to the helicity, such self-assembled cellulose structures preferentially reflect left-handed circularly polarized light of certain colors, while they remain transparent to right-handed circularly polarized light. This study shows that combination with a liquid crystal enables modulation of the optical response to obtain light reflection of both handedness but with reversed spectral profiles. As a result, the nanophotonic systems provide vibrant structural colors that are tunable via the incident light polarization. The results are attributed to the liquid crystal aligning on the CNC/glucose film, to form a birefringent layer that twists the incident light polarization before interaction with the chiral cellulose nanocomposite. Using a photoresponsive liquid crystal, this effect can further be turned off by exposure to UV light, which switches the nematic liquid crystal into a nonbirefringent isotropic phase. The study highlights the potential of hybrid cellulose systems to create self-assembled yet advanced photoresponsive and polarization-tunable nanophotonics.

9.
Nano Lett ; 20(10): 7243-7250, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32936657

RESUMO

Certain bird species have evolved spectacular colors that arise from organized nanostructures of melanin. Its high refractive index (∼1.8) and broadband absorptive properties enable vivid structural colors that are nonsusceptible to photobleaching. Mimicking natural melanin structural coloration could enable several important applications, in particular, for noniridescent systems with colors that are independent of incidence angle. Here, we address this by forming melanin photonic crystal microdomes by inkjet printing. Owing to their curved nature, the microdomes exhibit noniridescent vivid structural coloration, tunable throughout the visible range via the size of the nanoparticles. Large-area arrays (>1 cm2) of high-quality photonic microdomes could be printed on both rigid and flexible substrates. Combined with scalable fabrication and the nontoxicity of melanin, the presented photonic microdomes with noniridescent structural coloration may find use in a variety of applications, including sensing, displays, and anticounterfeit holograms.


Assuntos
Nanopartículas , Nanoestruturas , Biomimética , Óptica e Fotônica , Fótons
10.
Adv Funct Mater ; 30(31): 2002473, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32774202

RESUMO

High quality opal-like photonic crystals containing graphene are fabricated using evaporation-driven self-assembly of soft polymer colloids. A miniscule amount of pristine graphene within a colloidal crystal lattice results in the formation of colloidal crystals with a strong angle-dependent structural color and a stop band that can be reversibly shifted across the visible spectrum. The crystals can be mechanically deformed or can reversibly change color as a function of their temperature, hence their sensitive mechanochromic and thermochromic response make them attractive candidates for a wide range of visual sensing applications. In particular, it is shown that the crystals are excellent candidates for visual strain sensors or integrated time-temperature indicators which act over large temperature windows. Given the versatility of these crystals, this method represents a simple, inexpensive, and scalable approach to produce multifunctional graphene infused synthetic opals and opens up exciting applications for novel solution-processable nanomaterial based photonics.

11.
Adv Sci (Weinh) ; 8(1): 2001647, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33437570

RESUMO

The growing importance of human-machine interfaces and the rapid expansion of the internet of things (IoT) have inspired the integration of displays with sound generation systems to afford stretchable sound-in-display devices and thus establish human-to-machine connections via auditory system visualization. Herein, the synchronized generation of sound and color is demonstrated for a stretchable sound-in-display device with electrodes of strain-insensitive silver nanowires (AgNWs) and emissive layers of field-induced inorganic electroluminescent (EL) phosphors. In this device, EL phosphors embedded in a dielectric elastomer actuator (DEA) emit light under alternating-current bias, while audible sound waves are simultaneously generated via DEA actuation along with input sound signals. The electroluminescence and sound-generation performances of the fabricated device are highly robust and reliable, being insensitive to stretch-release cycling because of the presence of the AgNW stretchable electrodes. The presented principle of integrating light emission and acoustic systems in a single stretchable device can be further expanded to realize sound-in-display electronics for IoT and human-machine interface applications.

12.
Adv Mater ; 31(25): e1808148, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31070272

RESUMO

Biological tissues are multiresponsive and functional, and similar properties might be possible in synthetic systems by merging responsive polymers with hierarchical soft architectures. For example, mechanochromic polymers have applications in force-responsive colorimetric sensors and soft robotics, but their integration into sensitive, multifunctional devices remains challenging. Herein, a hierarchical nanoparticle-in-micropore (NP-MP) architecture in porous mechanochromic polymers, which enhances the mechanosensitivity and stretchability of mechanochromic electronic skins (e-skins), is reported. The hierarchical NP-MP structure results in stress-concentration-induced mechanochemical activation of mechanophores, significantly improving the mechanochromic sensitivity to both tensile strain and normal force (critical tensile strain: 50% and normal force: 1 N). Furthermore, the porous mechanochromic composites exhibit a reversible mechanochromism under a strain of 250%. This architecture enables a dual-mode mechanochromic e-skin for detecting static/dynamic forces via mechanochromism and triboelectricity. The hierarchical NP-MP architecture provides a general platform to develop mechanochromic composites with high sensitivity and stretchability.


Assuntos
Fenômenos Mecânicos , Nanopartículas , Dispositivos Eletrônicos Vestíveis , Cor , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Porosidade , Estresse Mecânico , Resistência à Tração
13.
Sci Adv ; 4(8): eaas8772, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30083604

RESUMO

We demonstrate ultrathin, transparent, and conductive hybrid nanomembranes (NMs) with nanoscale thickness, consisting of an orthogonal silver nanowire array embedded in a polymer matrix. Hybrid NMs significantly enhance the electrical and mechanical properties of ultrathin polymer NMs, which can be intimately attached to human skin. As a proof of concept, we present a skin-attachable NM loudspeaker, which exhibits a significant enhancement in thermoacoustic capabilities without any significant heat loss from the substrate. We also present a wearable transparent NM microphone combined with a micropyramid-patterned polydimethylsiloxane film, which provides excellent acoustic sensing capabilities based on a triboelectric voltage signal. Furthermore, the NM microphone can be used to provide a user interface for a personal voice-based security system in that it can accurately recognize a user's voice. This study addressed the NM-based conformal electronics required for acoustic device platforms, which could be further expanded for application to conformal wearable sensors and health care devices.


Assuntos
Acústica/instrumentação , Condutividade Elétrica , Monitorização Fisiológica/métodos , Nanofios/química , Prata/química , Pele/química , Dispositivos Eletrônicos Vestíveis , Eletrodos , Desenho de Equipamento , Humanos
14.
Adv Mater ; 30(28): e1800659, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29782678

RESUMO

Improved performance in plasmonic organic solar cells (OSCs) and organic light-emitting diodes (OLEDs) via strong plasmon-coupling effects generated by aligned silver nanowire (AgNW) transparent electrodes decorated with core-shell silver-silica nanoparticles (Ag@SiO2 NPs) is demonstrated. NP-enhanced plasmonic AgNW (Ag@SiO2 NP-AgNW) electrodes enable substantially enhanced radiative emission and light absorption efficiency due to strong hybridized plasmon coupling between localized surface plasmons (LSPs) and propagating surface plasmon polaritons (SPPs) modes, which leads to improved device performance in organic optoelectronic devices (OODs). The discrete dipole approximation (DDA) calculation of the electric field verifies a strongly enhanced plasmon-coupling effect caused by decorating core-shell Ag@SiO2 NPs onto the AgNWs. Notably, an electroluminescence efficiency of 25.33 cd A-1 (at 3.2 V) and a power efficiency of 25.14 lm W-1 (3.0 V) in OLEDs, as well as a power conversion efficiency (PCE) value of 9.19% in OSCs are achieved using hybrid Ag@SiO2 NP-AgNW films. These are the highest values reported to date for optoelectronic devices based on AgNW electrodes. This work provides a new design platform to fabricate high-performance OODs, which can be further explored in various plasmonic and optoelectronic devices.

15.
BMJ Case Rep ; 20182018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29592972

RESUMO

A 60-year-old woman with major depressive disorder, developed high blood pressure, confusion and dyskinesias of face, neck and jaw, following an increase in her dose of duloxetine. Routine blood tests including toxic, infective and metabolic workup were unremarkable. Cerebrospinal fluid analysis and electroencephalogram were also normal. MRI brain showed bilaterally symmetrical diffusion-restricted areas in deep cerebral white matter. Duloxetine was held on suspicion of drug adverse effect. She had complete resolution of symptoms within 48 hours and resolution of MRI brain changes over 6 weeks. Serotonin norepinephrine reuptake inhibitors such as duloxetine may have the potential to cause drug-induced movement disorders, confusion and high blood pressure and should be used cautiously especially in elderly.


Assuntos
Antidepressivos/efeitos adversos , Encéfalo/efeitos dos fármacos , Confusão/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Duloxetina/efeitos adversos , Transtornos dos Movimentos/etiologia , Encéfalo/diagnóstico por imagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade
16.
ACS Nano ; 11(4): 4346-4357, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28397485

RESUMO

Silver nanowire (AgNW) networks are considered to be promising structures for use as flexible transparent electrodes for various optoelectronic devices. One important application of AgNW transparent electrodes is the flexible touch screens. However, the performances of flexible touch screens are still limited by the large surface roughness and low electrical to optical conductivity ratio of random network AgNW electrodes. In addition, although the perception of writing force on the touch screen enables a variety of different functions, the current technology still relies on the complicated capacitive force touch sensors. This paper demonstrates a simple and high-throughput bar-coating assembly technique for the fabrication of large-area (>20 × 20 cm2), highly cross-aligned AgNW networks for transparent electrodes with the sheet resistance of 21.0 Ω sq-1 at 95.0% of optical transmittance, which compares favorably with that of random AgNW networks (sheet resistance of 21.0 Ω sq-1 at 90.4% of optical transmittance). As a proof of concept demonstration, we fabricate flexible, transparent, and force-sensitive touch screens using cross-aligned AgNW electrodes integrated with mechanochromic spiropyran-polydimethylsiloxane composite film. Our force-sensitive touch screens enable the precise monitoring of dynamic writings, tracing and drawing of underneath pictures, and perception of handwriting patterns with locally different writing forces. The suggested technique provides a robust and powerful platform for the controllable assembly of nanowires beyond the scale of conventional fabrication techniques, which can find diverse applications in multifunctional flexible electronic and optoelectronic devices.

17.
Jundishapur J Microbiol ; 8(10): e23567, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26587211

RESUMO

BACKGROUND: Thrombolytic therapy has become a conventional treatment for acute myocardial infarction (AMI), yet currently, clinically prescribed thrombolytic drugs have problems such as delayed action and other side effects. Fibrinolytic enzymes have attracted interest as thrombolytic agents because of their efficiency in the fibrinolytic process, including plasmin activation. Nattokinase (NK) is a potent fibrinolytic agent for thrombosis therapy. OBJECTIVES: The aim of this study was to enhance the production of NK from Pseudomonas aeruginosa CMSS by media optimization and strain improvement. MATERIALS AND METHODS: In the present study, a potent NK-producing strain was isolated from cow milk and identified. To enhance the yield of NK, effect of various parameters such as pH, temperature, carbon source, nitrogen source and inoculum size were optimized. Strain improvement of P. aeruginosa CMSS was done by random UV-mutagenesis. Nattokinase was partially purified and the activity was determined by the casein digestion method, blood clot lysis and fibrin degradation assay. RESULTS: Based on morphological, biochemical and molecular characterization, the strain was confirmed as P. aeruginosa (GenBank accession number: JX112657), designated as P. aeruginosa CMSS. The optimum condition at pH 7 and temperature at 25˚C showed activity of NK as 1514 U mL(-1) and 1532 U mL(-1), respectively. Sucrose as the carbon source and shrimp shell powder (SSP) as the nitrogen source expressed NK activity of 1721 U mL(-1) and 2524 U mL(-1), respectively. At 1% inoculum size, the maximum rate of enzyme production was achieved with 2581 U mL(-1). The NK activity of the mutant strain UV60 was 4263 U mL(-1), indicating a two-fold increase in activity compared to the wild strain (2581 UmL(-1)). Nattokinase produced from mutant strain P. aeruginosa CMSS UV60 showed 94% blood clot lysis at ten minutes. The degradation of fibrin clot by the produced NK was observed after two hours of incubation. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) confirmed the molecular mass of CMSS UV60 NK to be 21kDa. CONCLUSIONS: The current study demonstrated the enhanced production of NK by P. aeruginosa CMSS. This study is unique and the findings are the first report on the production of NK from P. aeruginosa CMSS isolated from cow milk.

18.
ACS Nano ; 8(9): 8819-30, 2014 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-25100211

RESUMO

Monitoring of human bodily motion requires wearable sensors that can detect position, velocity and acceleration. They should be cheap, lightweight, mechanically compliant and display reasonable sensitivity at high strains and strain rates. No reported material has simultaneously demonstrated all the above requirements. Here we describe a simple method to infuse liquid-exfoliated graphene into natural rubber to create conducting composites. These materials are excellent strain sensors displaying 10(4)-fold increases in resistance and working at strains exceeding 800%. The sensitivity is reasonably high, with gauge factors of up to 35 observed. More importantly, these sensors can effectively track dynamic strain, working well at vibration frequencies of at least 160 Hz. At 60 Hz, we could monitor strains of at least 6% at strain rates exceeding 6000%/s. We have used these composites as bodily motion sensors, effectively monitoring joint and muscle motion as well and breathing and pulse.


Assuntos
Grafite/química , Monitorização Fisiológica/instrumentação , Movimento , Borracha/química , Estresse Mecânico , Elasticidade , Humanos
19.
Pharmacol Rev ; 65(1): 315-499, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23383426

RESUMO

Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.


Assuntos
Descoberta de Drogas , Preparações Farmacêuticas/química , Animais , Soluções Tampão , Cristalização , Ciclodextrinas/química , Humanos , Lipídeos/química , Tamanho da Partícula , Sais/química , Solubilidade , Solventes/química , Tensoativos/química
20.
J Pharm Sci ; 100(10): 4349-56, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21630280

RESUMO

A method is described for screening compounds that inhibit crystallization in solution to enable more accurate measurement of amorphous drug solubility. Three polymers [polyvinylpyrrolidone, hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose acetate succinate (HPMCAS)] were screened for their ability to inhibit the crystallization of neat amorphous drugs during measurement of solubility of the amorphous form in water. Among the polymers evaluated, HPMCAS was found to be most promising. The use of HPMCAS provided an "apparent solubility" of amorphous drugs that was closer to the theoretically calculated values. With danazol, agreement was essentially quantitative, and for griseofulvin and iopanoic acid, agreement was within a factor of two; these maximum concentrations were sustained for a period of 40-90 min. Dynamic light scattering of filtered samples (0.22 µ) revealed the presence of colloidal drug-polymer assemblies in solution (100-150 nm). The supernatant resulting from this centrifugation gradually decreased in concentration, but remained supersaturated with respect to crystalline drug for several hours. Thus, HPMCAS has been shown to be a useful additive in dissolution media to allow a more accurate determination of the solubility of fast crystallizing neat amorphous drugs, at least for the drugs studied, and it should also serve to retard crystallization in vivo and therefore, facilitate improved bioavailability.


Assuntos
Metilcelulose/análogos & derivados , Preparações Farmacêuticas/química , Química Farmacêutica , Coloides , Cristalização , Danazol/química , Griseofulvina/química , Derivados da Hipromelose/química , Ácido Iopanoico/química , Cinética , Luz , Metilcelulose/química , Povidona/química , Espalhamento de Radiação , Solubilidade , Tecnologia Farmacêutica/métodos , Ultracentrifugação
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