Development of inclusion complex based on cyclodextrin and oxazolidine derivative

Abstract Oxazolidine derivatives (OxD) have been described as third-line antibiotics and antitumoral agents. The inclusion complexes based on cyclodextrin could improve the solubility and bioavailability of these compounds. A novel synthetic OxD was used, and its inclusion complexes were based on 2-hydroxy-beta-cyclodextrin (2-HPßCD). We conducted an in silico study to evaluate the interaction capacity between OxD and 2-HPßCD. Characterization studies were performed through scanning electron microscopy (SEM), Fourier-transformed infrared (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), X-ray diffraction (XRD), and thermal analyses. A kinetic study of the OxD was performed, including a cytotoxicity assay using peripheral blood mononuclear cells (PBMCs). The maximum increment of solubility was obtained at 70 mM OxD using 400 mM 2-HPßCD. SEM analyses and FTIR spectra indicated the formation of inclusion complexes. 1H-NMR presented chemical shifts that indicated 1:1 stoichiometry. Different thermal behaviors were obtained. The pharmacokinetic profile showed a short release time. Pure OxD and its inclusion complex did not exhibit cytotoxicity in PBMCs. In silico studies provided a foremost insight into the interactions between OxD and 2-HPßCD, including a higher solubility in water and an average releasing profile without toxicity in normal cells

Análise de metodologias para avaliação da solubilidade do cimento à base de silicato de cálcio Bio-C Sealer / Analysis of methodologies for evaluating the solubility of calcium silicate-based sealer Bio-C Sealer

Introdução: Cimentos endodônticos à base de silicato de cálcio demonstram maior solubilidade em água destilada. Emprego de metodologias alternativas pode auxiliar em melhor compreensão sobre a solubilidade desses materiais. Objetivo: Avaliar o efeito da solução de imersão e do tipo de modelo experimental na solubilidade de cimento pronto para uso Bio-C Sealer. Material e método: Modelos circulares de polietileno ou dentina bovina (n = 16) foram confeccionados. Após inserção do cimento, os espécimes foram mantidos em estufa a 37 °C por 48 horas. Posteriormente, as amostras foram pesadas em balança de precisão para determinação da massa inicial. Na sequência, os espécimes foram imersos em 7,5 mL de água destilada (pH 6,5) ou PBS (pH 7,0) (n = 8) por 28 dias. Após isso, as amostras foram removidas das soluções e pesadas a cada 24 horas até a estabilização da massa final (0,001g). Corpos de prova confeccionados com Bio-C Sealer foram empregados como controle. A solubilidade foi avaliada de acordo com a diferença entre a massa inicial e final em porcentagem. Teste ANOVA Two-Way e teste post-hoc de Tukey foram realizados (α = 0,05). Resultado: Imersão em água destilada proporcionou maior solubilidade em comparação com PBS, independentemente do modelo experimental (p < 0,05). Corpos de prova apresentaram maior solubilidade, seguidos dos modelos de polietileno e dentina imersos em água destilada (p < 0,05). Não houve diferença entre os modelos experimentais imersos em PBS (p > 0,05). Conclusão: Bio-C Sealer apresenta solubilidade significativamente maior em água destilada do que em PBS em todas condições. Modelo experimental empregando dentina bovina e PBS como solução de imersão demonstra diminuir a perda de massa de Bio-C Sealer e pode ser uma alternativa valiosa para avaliar a solubilidade de cimentos biocerâmicos

Introduction: Calcium silicate-based sealers demonstrate greater solubility in distilled water. The use of alternative methodologies can help at better understanding the solubility of these materials. Objective: To evaluate the effect of the immersion solution and the type of experimental model on the solubility of readyto-use Bio-C Sealer. Material and method: Circular models of polyethylene or bovine dentin (n = 16) were made. After insertion of the sealer, the specimens were kept in an oven at 37°C and 95% humidity for 48h. Subsequently, the samples were weighed on a precision balance to determine the initial mass. Next, the specimens were immersed in 7.5 mL of distilled water (pH 6.5) or PBS (pH 7.0) (n = 8) for 28 days. After that, the samples were removed from the solutions and weighed every 24 hours until the final mass stabilized (0.001g). Test specimens made with Bio-C Sealer were used as a control. Solubility was evaluated according to the difference between the initial and final mass in percentage. Two-Way ANOVA test and Tukey post-hoc tests were performed (α=0.05). Result: Immersion in distilled water provided greater solubility compared to PBS regardless of the experimental model (p<0.05). The test specimens showed greater solubility, followed by polyethylene and dentin models immersed in distilled water (p<0.05). There was no difference between the experimental models immersed in PBS (p>0.05). Conclusion: Bio-C Sealer presents significantly greater solubility in distilled water than in PBS under all conditions. Experimental model using bovine dentin and PBS as an immersion solution demonstrates reduction in the mass loss of Bio-C Sealer and can be a valuable alternative for evaluating the solubility of bioceramic sealers

Technology and principle of improving solubility of Dioscoreae Rhizoma formula granules based on powder modification / 中国中药杂志

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) μm to(37.91±0.42) μm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.

PVP solid dispersions containing Poloxamer 407 or TPGS for the improvement of ursolic acid release

Abstract Solid dispersions (SDs) of ursolic acid (UA) were developed using polyvinylpyrrolidone K30 (PVP K30) in combination with non-ionic surfactants, such as D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or poloxamer 407 (P407) with the aim of enhancing solubility and in vitro release of the UA. SDs were investigated using a 24 full factorial design, subsequently the selected formulations were characterized for water solubility, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), particle diameter, scanning electron microscopy, drug content, physical-chemical stability and in vitro release profile. SDs showed higher UA water-solubility than physical mixtures (PMs), which was attributed by transition of the drug from crystalline to amorphous or molecular state in the SDs, as indicated by XRD and DSC analyses. SD1 (with P407) and SD2 (with TPGS) were chosen for further investigation because they had higher drug load. SD1 proved to be more stable than SD2, revealing that P407 contributed to ensure the stability of the UA. Furthermore, SD1 and SD2 increased UA release by diffusion and swelling-controlled transport, following the Weibull model. Thus, solid dispersions obtained with PVP k-30 and P407 proved to be advantageous to enhance aqueous solubility and stability of UA.

Influence of solvent choice and operating conditions on Chlorzoxazone crystal shape and size

Abstract Solubility of pharmaceutical drugs in organic solvents is one of the important parameters to understand the equilibrium concentration of solute-solvent, which helps optimize and design crystallization conditions to obtain the desired product crystals. In the present study, Chlorzoxazone (CHZ) is used as a model pharmaceutical compound to investigate the equilibrium solubility, the influence of solvent and the operating conditions on the shape, and the size distribution. The solubility of CHZ is determined in organic solvents like Isopropanol, Ethanol, and 2-Ethoxyethylacetate, Ethylacetate and Ethyllactate using shake flask method from -5ºC to 60ºC. The solubility of CHZ in these solvents shows an increasing trend as the temperature increases in the following order: ethyllactate + water (0.5+0.5) < ethylacetate < isopropanol < ethanol < 2-ethoxyethylacetate < ethyllactate + water (0.75+0.25). The solvents, isopropanol, ethanol, and ethyl lactate, produce needle-shaped crystals, while 2-ethoxyethylacetate and ethyl acetate tend to produce plate shaped crystals. CHZ crystals obtained from 2-ethoxyethylacetate tend to have plate shaped crystals with a lower aspect ratio and are selected for batch cooling crystallization experiments performed at different cooling rates, and agitation. It is found that the agitation at 300 rpm and the cooling rate 0.2ºC/min produce more uniform crystal size distribution

Avaliação da sorção e solubilidade de água em cimentos de ionômero de vidro com e sem agente de proteção / Evaluation of water sorption and solubility in glass ionomer cements with and without protective agent

Objetivo: Avaliar o efeito de um protetor de superfície na sorção e solubilidade de cimentos de ionômero de vidro. Materiais e Métodos: Quatro materiais foram selecionados: ionômero modificado por resina encapsulado (Riva Light Cure); modificado por resina pó/líquido (Vitremer); convencional encapsulado (Equia Forte) e convencional pó/líquido (Fuji IX). Foram confeccionados 20 espécimes de cada, sendo metade com proteção superficial do Equia Forte Coat. As amostras foram mantidas em estufa a 37°C em repouso por 5 dias. Em seguida, esses foram pesados em intervalos de 24 horas. A espessura e o diâmetro foram medidos com um paquímetro digital para o cálculo do volume. Novas pesagens foram realizadas para a obtenção da massa intermediária. Em seguida, as amostras foram mantidas em repouso por 5 dias a 37°C e realizada nova pesagem. Resultados: Os dados obtidos de sorção e solubilidade foram submetidos à análise de variância (ANOVA dois fatores, material e protetor de superfície) e teste Tukey ( =0,05). Para sorção, houve diferença significativa apenas para o fator material (p<0,05), Vitremer > Equia Forte > Riva Light Cure > Fuji IX. O ionômero Fuji IX apresentou os menores valores de sorção, diferindo significativamente dos demais materiais, independentemente do uso do protetor superficial. Não houve diferença significativa para o fator proteção de superfície (p>0,05). Para solubilidade não houve diferença significativa no fator material, protetor de superfície ou interação material*protetor. Conclusão: O uso do protetor superficial não influenciou nos valores de sorção e solubilidade dos ionômeros avaliados e o ionômero convencional Fuji IX apresentou menores taxas de sorção.

Objective: evaluate the effect of a surface coating agents on the sorption and glass ionomer cements solubility. Materials and Methods: Four materials were selected: Encapsulated resin-modified ionomer (Riva Light Cure); Powder/liquid Encapsulated resin-modified (Vitremer); Encapsulated conventional (Equia Forte) and powder/ liquid conventional (Fuji IX). Twenty samples of each were made, half with surface protection of Equia Forte Coat. The samples were kept in an oven for 5 days. These were then weighed at 24-hour intervals. The thickness and diameter were measured using a digital caliper to calculate their volume. New weightings were performed to obtain the intermediate mass. Then, the samples were kept at rest for 5 days and weighed again. Results: The sorption and solubility data obtained were subjected to analysis of variance (two-way ANOVA, material and surface coating agents) and Tukey test ( =0.05). For sorption, there was a significant difference only for the material factor (p<0.05), Vitremer > Equia Forte > Riva Light Cure > Fuji IX. The Fuji IX ionomer showed the lowest sorption values, differing significantly from the other materials, regardless of the use of surface coating agents. There was no significant difference for the surface protection factor (p>0.05). For solubility there was no significant difference for the material factor, surface coating agents or material*surface coating agent interaction. Conclusion: The use of surface coating agents did not influence the sorption and solubility values of the evaluated ionomers and the conventional Fuji IX ionomer showed lower sorption rates.

The relationships among Flory-Huggins specific interaction parameters, maximum amorphous capacity, and solid-state interactions of spray dried amorphous drug dispersions with conventional and novel pharmaceutical polymers / Las relaciones entre los parámetros de interacción específicos de Flry-Huggins, la capacidad amorfa máxima y las interacciones en estado sólido de las dispersiones de fármacos amorfos secados por aspersión con polímeros farmacéuticos convencionales y nuevos

This study evaluated the specific interactions between drug and polymers in amorphous spray dried dispersions (SDDs). Four Biopharmaceutics Classification System (BCS) II class drugs were evaluated. Binary and ternary SDDs were manufactured with conventional polymers and arabinogalactan. Specific interaction parameters between drug and polymer were determined using theoretical calculations and DSC data. Analytical methods were used to evaluate solid and solution state interactions. Maximum amorphous content for each formulation was calculated using DSC. Flory-Huggins Specific Interaction Parameters were calculated. Negative specific parameters were associated with solid-state interactions and improved capacity of drug in the amorphous state. Ternary SDDs containing drug, polymer, and arabinogalactan displayed similar hydrogen bonding as was observed with binary SDDs. Solution-state interactions observed in binary systems may be used in tertiary systems to improve the amorphous drug capacity and improved dissolution compared to the binary. The resultant tertiary systems are an improvement over binary drug polymer systems.

Este estudio evaluó las interacciones específicas entre el fármaco y los polímeros en dispersiones amorfas secadas por pulverización (SDD). Se evaluaron cuatro fármacos de clase II del Sistema de Clasificación Biofarmacéutica (BCS). Los SDD binarios y ternarios se fabricaron con polímeros convencionales y arabinogalactano. Los parámetros de interacción específicos entre el fármaco y el polímero se determinaron utilizando cálculos teóricos y datos de DSC. Se utilizaron métodos analíticos para evaluar las interacciones del estado sólido y de la solución. El contenido amorfo máximo para cada formulación se calculó usando DSC. Se calcularon los parámetros de interacción específicos de Flory-Huggins. Los parámetros específicos negativos se asociaron con interacciones en estado sólido y una capacidad mejorada del fármaco en el estado amorfo. Los SDD ternarios que contienen fármaco, polímero y arabinogalactano mostraron enlaces de hidrógeno similares a los observados con los SDD binarios. Las interacciones de estado de solución observadas en sistemas binarios pueden usarse en sistemas terciarios para mejorar la capacidad del fármaco amorfo y mejorar la disolución en comparación con el binario. Los sistemas terciarios resultantes son una mejora con respecto a los sistemas de polímeros de fármacos binarios.

A comparison of the physicochemical properties of AH Plus Jet with samples taken from the beginning, middle and final portions of the automix syringe system

Aim To evaluate physicochemical properties and semi-quantitative elemental analysis of AH Plus Jet with samples from the beginning, middle and final portions of the automix syringe system. Methodology Three experimental groups based on the source of the material used (beginning, middle and final portion) were established for each of the evaluated properties. Setting time, flow and radiopacity were evaluate following ANSI/ADA n. 57 specification. Set specimens was used in the semi-quantitative elemental analysis in an energy-dispersive X ray spectroscopy and scanning-electron microscopy (EDS/SEM). Statistical analysis was performed using one-way ANOVA followed by Tukey test (P<0.05). Results Flow, setting time, solubility and EDS/SEM tests showed no significant differences among the three portions of the automix syringe (P>0.05). Radiopacity test showed significant differences in the beginning of the syringe comparing to the middle and final portions (P<0.05). EDS/SEM analysis identified the presence of C, O, Al, Ca, Zr and W. The element Al, however, was found only in the final portion of the syringe. Conclusions The results of AH Plus Jet suggested an adequate ratio of the components, without segregation between organic and inorganic components, since the results of setting time, flow, solubility and EDS/SEM analysis presented similar values regardless of the portion of the syringe from where the sealer was taken.

Spray-dried co-amorphous Tadalafil ternary mixtures: a promising platform towards the enhancement of solubility and bioavailability

Abstract Tadalafil (Tad) is a poorly water-soluble drug (BCS class II) that is used for the treatment of erectile dysfunction. An enhancement of aqueous solubility is vital to accelerate its onset of action and subsequently enhance its therapeutic effect. Binary and ternary mixtures of Tad with different amino acids (histidine, valine, alanine or arginine) and other excipients (mannitol and SLS) were prepared and then spray dried. The solubilizing efficiency and physicochemical characterization of all spray dried mixtures of Tad were studied. The optimum formulation was investigated in male rats to determine the onset of erection and the pharmacokinetic parameters of Tad. In general terms, the drug solubility of spray-dried formulae was enhanced compared to the crystalline form of the drug as a result of the formation of co-amorphous structures. The final result revealed that the Tad/alanine/mannitol spray-dried mixture (F10) showed the highest solubility and an improvement in its physicochemical characteristics. Moreover, F10 showed a significantly faster erection in rats with an improvement in Tad pharmacokinetic parameters when compared to the crystalline drug. Thus, F10 is selected as a promising formulation that successfully enhanced the bioavailability and the therapeutic efficacy of Tad.

Dissolution profile of different brands of low solubility drugs available in the Nigerian and Brazilian pharmaceutical markets / Dissolution profile of different brands of low solubility drugs available in the Nigerian and Brazilian pharmaceutical markets

The purpose of this work was to elaborate a diagnosis of the dissolution test in Africa in comparison with Brazil, evaluating the dissolution profile of low solubility drugs such as albendazole, ibuprofen, furosemide, glibenclamide, hydrochlorothiazide and carvedilol to ascertain their quality. The dissolution profiles were evaluated by utilizing the United States Pharmacopeia (USP). The glibenclamide medicine was evaluated according to the Food and Drug Administration (FDA), while a dissolution method was developed for the carvedilol medicine. A filter selection test for all the drugs showed that cannula is suitable for all, except for carvedilol, which is centrifuged. The various brands of Nigerian and Brazilian medicines tested showed some statistical differences. The suitable conditions that allowed the dissolution of carvedilol to be determined were the USP type II apparatus at 75 rpm containing 900 mL of acetate buffer, pH 4.5. The results of the dissolution test showed that out of the 17 different brands of Brazilian medicines and 17 different products from Nigeria, 94.12% and 58.82% passed respectively

O objetivo deste trabalho foi elaborar um diagnóstico do teste de dissolução na África em comparação ao Brasil, avaliando o perfil de dissolução de medicamentos de baixa solubilidade como albendazol, ibuprofeno, furosemida, glibenclamida, hidroclorotiazida e carvedilol para verificar sua qualidade.Os perfis de dissolução foram avaliados utilizando a Farmacopeia dos Estados Unidos (USP). O medicamento glibenclamida foi avaliado de acordo com a Food and Drug Administration (FDA), enquanto um método de dissolução foi desenvolvido para o medicamento carvedilol.Um teste de seleção de filtro para todos os medicamentos mostrou que a cânula é adequada para todos, exceto para o carvedilol, que é centrifugado. As diversas marcas de medicamentos Nigerianos e Brasileiros testadas apresentaram algumas diferenças estatísticas. As condições adequadas que permitiram a determinação da dissolução do carvedilol foram o aparelho USP tipo II a 75 rpm contendo 900 mL de tampão acetato, pH 4,5. Os resultados do teste de dissolução mostraram que das 17 diferentes marcas de medicamentos brasileiros e 17 diferentes produtos da Nigéria, 94,12% e 58,82% foram aprovados, respectivamente

A influência da sorção e solubilidade nas propriedades dos compósitos resinosos: uma revisão de literatura / The influence of sorption and solubility on the properties of res-in composites: a literature review

Introdução: A resina composta tem sido amplamente utilizada por suas propriedades restauradoras. No entanto, quando exposta à água, o material resinoso sofre diferentes mecanismos químicos e físicos, como a sorção de água e solubilidade. Esses efeitos podem produzir alterações volumétricas e mudanças físicas, alterando as características do material. Objetivo: Discorrer acerca das consequências clínicas dos fenômenos de sorção e solubilidade na resina composta. Materiais e Métodos: Uma revisão da literatura foi realizada por meio de artigos científicos publicados nos últimos anos, presentes em bases de dados eletrônicos como PubMED/Medline, Lilacs e Scielo. Resultados e Discussão: Os compósitos de resina não são estáveis, pois interagem constantemente com o ambiente oral. Sua principal interação é com água, que se difunde na matriz. As resinas compostas que contêm, além do BIS-GMA, uma alta concentração de TEGDMA, tendem a absorver mais água devido às ligações éter hidrofílicas presentes nesses compósitos. Com isso, uma série de efeitos deletérios podem ocorrer. Conclusão: A expansão volumétrica, a lixiviação, a degradação hidrolítica e a instabilidade da cor são as principais consequências da sorção e solubilidade da resina composta. Esses fenômenos provocam alterações dimensionais e diminuição das propriedades mecânicas repercutindo, sobremaneira, na longevidade das restaurações em resina composta.

Introduction: Resin Composite has been widely used for its restorative properties. However, when exposed to water, the resin material undergoes different chemical and physical mechanisms, such as water sorption and solubility. These effects can produce volumetric and physical changes, altering the material's characteristics. Objective: To discuss the clinical consequences of the sorption and solubility phenomena in composite resin. Materials and Methods: A literature review was performed using scientific articles published in recent years on electronic databases such as PubMED/Medline, Lilacs, and Scielo. Results and Discussion: Resin composites are not stable, as they constantly interact with the oral environment. Their main interaction is with water, which diffuses into the matrix. Resin Composites that contain, in addition to BIS-GMA, a high concentration of TEGDMA, tend to absorb more water due to the hydrophilic ether bonds present in these composites. Thus, a series of deleterious effects can occur. Conclusion: Volumetric expansion, leaching, hydrolytic degradation, and color instability are the main consequences of Resin Composite sorption and solubility. These phenomena cause dimensional changes and a decrease in mechanical properties, which have a major impact on the longevity of Resin Composite restorations.

Co-amorphous technology to improve dissolution and physical stability of silybin / 中国中药杂志

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.

Estudo da permeabilidade de fármacos por meio do modelo de saco intestinal de ratos / Study of drug permeability through the rat gut sac model

Os parâmetros de permeabilidade e solubilidade são fundamentais à absorção oral de fármacos e a partir dessas características, foi criado o Sistema de Classificação Biofarmacêutica, através do qual os fármacos são divididos em quatro classes. Atualmente, para a determinação da solubilidade de um fármaco, existem diversos métodos padronizados por agências regulatórias, no entanto, para a determinação da permeabilidade, os ensaios são passíveis de diversas variações em sua execução, diminuindo a confiabilidade dos resultados obtidos e impossibilitando a comparação dos mesmos quando realizados com técnicas diferentes umas das outras. O objetivo do presente trabalho é avaliar as variáveis experimentais do modelo do saco intestinal que podem influenciar nos resultados de permeabilidade aparente de fármacos e na viabilidade do tecido. O presente estudo foi aprovado pelo Comitê de Ética no Uso de Animais da FCF-USP (109.2018-P574). Foram utilizados 33 Rattus norvegicus da linhagem Wistar, machos, jovens adultos, com peso entre 200 g e 300 g. Para realização do procedimento, cada animal permaneceu em jejum por cerca de quatro horas e após adequada anestesia a porção do jejuno do intestino delgado foi retirada e dividida em seis segmentos de aproximadamente 8,5cm cada. Foram realizados experimentos com e sem inversão do saco intestinal, submetidos a diferentes tempos de banho de gelo após sua ressecção, na presença ou ausência de inibidor da glicoproteína-P (verapamil). Os fármacos naproxeno e famotidina foram empregados como marcadores de alta e baixa permeabilidade, respectivamente. A losartana foi utilizada como substrato da glicoproteína P. Cada um dos sacos intestinais foi colocado em um tubo de ensaio contendo tampão Krebs, a 37°C, saturado com gás carbogênio. Para avaliação da integridade e viabilidade dos segmentos intestinais, observou-se a presença de movimentos peristálticos e coletaram-se amostras do meio de incubação nos tempos 0, 30, 45, 60, 90 e 120 minutos para quantificação dos fármacos e de glicose, uma vez que esta é ativamente transportada para a serosa do intestino delgado. Determinou-se a permeabilidade aparente de cada fármaco e as concentrações de glicose nas diferentes condições experimentais, realizou-se planejamento fatorial multinível e os resultados foram analisados por análise variância (ANOVA), seguida de pós-teste de Tukey. Observou-se que as variáveis experimentais interferiram de forma significativa na viabilidade tecidual e na permeabilidade aparente dos fármacos. Não foram observadas diferenças significativas da permeabilidade de fármacos nos diferentes segmentos do jejuno. A glicose mostrou-se um bom marcador de viabilidade tecidual e foi constatado que a presença ou ausência de movimentos peristálticos não está relacionada diretamente com a viabilidade do tecido. Uma vez que foram constatadas tantas interferências nos resultados, é imprescindível que os procedimentos experimentais sejam padronizados, para que os resultados apresentem menor variabilidade e possam ser comparados entre si

The permeability and solubility parameters are fundamental to the oral absorption of drugs and from these characteristics, the Biopharmaceutical Classification System was created, through which drugs are divided into four classes. Currently, for the determination of the solubility of a drug, there are several methods standardized by regulatory agencies, however, for the determination of permeability, the tests are subject to several variations in their execution, reducing the reliability of the results obtained and making it impossible to compare the results obtained. same when performed with different techniques. The aim of this study is to evaluate if different experimental conditions can influence the results of apparent drug permeability and tissue viability on gut sac model. The present study was approved by the Ethics Committee for the Use of Animals of FCF-USP (109.2018-P574). Thirty-three male, young adult Rattus norvegicus were used, weighing between 200 g and 300 g. To perform the procedure, each animal fasted for about four hours and after adequate anesthesia, the portion of the jejunum of the small intestine was removed and divided into six segments of approximately 8.5 cm each. Experiments were performed with and without inversion of the gut sac, submitted to different times of ice bath after its resection, in the presence or absence of a P-glycoprotein inhibitor (verapamil). The drugs naproxen and famotidine were used as markers of high and low permeability, respectively. Losartan was used as a substrate for P-glycoprotein. Each of the gut sacs was placed in a test tube containing Krebs buffer, at 37°C, saturated with carbogen gas. To evaluate the integrity and viability of the intestinal segments, the presence of peristaltic movements was observed and samples of the incubation medium were collected at 0, 30, 45, 60, 90 and 120 minutes for quantification of drugs and glucose, as it is actively transported to the serosa of the small intestine. The apparent permeability of each drug and the glucose concentrations were determined under different experimental conditions, multilevel factorial design was performed and the results were analyzed by analysis of variance (ANOVA), followed by Tukey's post-test. It was observed that the experimental variables significantly interfered in the tissue viability and in the apparent permeability of the drugs. No significant differences in drug permeability were observed in the different segments of the jejunum. Glucose proved to be a good marker of tissue viability and it was found that the presence or absence of peristaltic movements is not directly related to tissue viability. Since so many interferences were found in the results, it is essential that the experimental procedures be standardized, so that the results show less variability and can be compared between different authors

Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation

Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.

Effect of delayed light-curing on solubility, color stability, and opacity of Fuji II LC glass ionomer cement: original article / Efeito da fotopolimerização tardia na solubilidade, estabilidade de cor e opacidade do cimento de ionômero de vidro Fuji II LC: artigo original

Objective: Resin-modified glass ionomer (RMGI) cements are among the commonly used restorative materials in low stress-bearing areas and also for temporary restorations. The competition between acid-base reactions and light polymerization reactions in delayed curing of RMGIs can affect their physical and mechanical properties, as well as their degree of conversion. Since solubility, color stability, and opacity are among the main physical properties affecting the durability and clinical service of RMGI restorations, this study aimed to assess the effect of delayed curing on solubility, color stability, and opacity of Fuji II LC RMGI. Material and Methods: This in vitro, experimental study evaluated 80 Fuji II LC RMGI specimens (10 specimens per each in 4 groups) in terms of solubility, color stability, and opacity at 6 months later. Specimens were cured immediately or were cured with 1, 5 and 10 min delay. Results: Maximum solubility and minimum change in opacity and color stability at 6 months were noted in the group with delayed curing by 10 min. A significant difference was noted in the solubility of specimens cured after 10 min and 1 min. Significant differences were also noted in the opacity and color stability of specimens cured after 10 min and all other groups (P < 0.05). Conclusion: Delayed curing by 1 min decreased the solubility of RMGI specimens compared with immediate curing or curing after 5 min. Although this difference did not reach statistical significance. Color stability and changes in opacity are mainly influenced by the acid-base reactions rather than polymerization reactions.(AU)

Objetivo: Cimentos de ionômero de vidro modificado por resina (CIVMR) estão entre os materiais restauradores mais comumente utilizados em áreas de baixa tensão e também para restaurações temporárias. A competição entre reações ácido-base e reações provenientes da fotopolimerização tardia dos CIVRMs podem afetar suas propriedades físicas e mecânicas, bem como seu grau de conversão. Uma vez que a solubilidade, estabilidade de cor e opacidade estão entre as principais propriedades físicas que afetam a durabilidade e o tempo de serviço clinico de restaurações de CIVMR, este estudo teve como objetivo avaliar o efeito da fotopolimerizaçao tardia na solubilidade, estabilidade de cor e opacidade do CIVMR Fuji II LC. Material e Métodos: Este estudo experimental in vitro avaliou 80 espécimes de CIVMR Fuji II LC (4 grupos com 10 espécimes cada) em termos de solubilidade, estabilidade de cor e opacidade apos 6 meses. As amostras foram fotopolimerizadas imediatamente ou com 1, 5 e 10 min de atraso. Resultados: Máxima solubilidade e mínima alteração na opacidade e estabilidade da cor em 6 meses foram observadas no grupo com fotopolimerização tardia em 10 min. Uma diferença significativa foi observada na solubilidade das amostras fotopolimerizadas após 10 min e 1 min. Diferenças significativas também foram observadas na opacidade e estabilidade de cor das amostras fotopolimerizadas após 10 min e em todos os outros grupos (P <0,05). Conclusão: A fotopolimerizaçao tardia em 1 min diminuiu a solubilidade das amostras CIVMR em comparação com a fotopolimerizaçao imediata ou após 5 min. Embora essa diferença não tenha alcançado significância estatística. A estabilidade da cor e as mudanças na opacidade são influenciadas principalmente por reações ácido-base, em vez de reações causadas pela polimerização(AU)

Incorporation of a polymerization catalyst for improved mechanical behavior and physicochemical characteristics of a light-cured pulp capping material / Incorporação de um catalisador de polimerização para aprimorar propriedades mecânicas e fisíco-químicas de um protetor pulpar fotoativável

Objective: To evaluate the influence of the incorporation of a polymerization catalyst to a light-cured pulp capping material on mechanical behavior and physicochemical characteristics. Material and Methods: Different percentages (2 wt%, and 4 wt%) of diphenyliodonium hexafluorophosphate (DPI) were incorporated into the Ultra-Blend Plus, a resin-modified calcium-based cement. The material without incorporation of DPI (0 wt%) served as control. Degree of Conversion (DC), Flexural Strength (FS), Elastic Modulus (EM), Water Sorption (WSp), Solubility (Sl), and pH of eluate at 24-h, 72-h, and 7-day storage times were measured. One-way ANOVA/Tukey posthoc tests were used to analyze the data (p <0.05). Results: For DC, FS, and EM, materials with different % of DPI showed statistically significant differences, so that 0% provided the lowest values and 2% the highest values. Materials with 0% and 2% of DPI provided statistically the lowest WSp, whilst material with 0% of DPI showed statistically the highest Sl. Conclusion: All materials provided statistically similar pH to eluates regardless of storage time, although only materials with DPI at 2% and 4% maintained pH of eluates statistically similar from 72 h to 7 days storage times.(AU)

Objetivo: avaliar a influência nas propriedades mecânicas e físico-químicas da incorporação de um catalisador de polimerização a um protetor pulpar fotoativável. Material e Métodos: foram adicionadas diferentes porcentagens em massa (2% e 4%) de hexafluorofosfato de difeniliodônio (DPI) ao Ultra-Blend Plus, um cimento à base de hidróxido de cálcio modificado por resina. O material sem a adição do DPI (0%) serviu como controle. Foram avaliados: Grau de Conversão (DC), Resistência Flexural (FS), Módulo de Elasticidade (EM), Sorção (WSp), Solubilidade (SI) e o pH do eluato nos tempos de 24h, 72h e 7 dias de armazenamento. ANOVA 1-way com pós-teste de Tukey (p <0.05). Foi utilizado para avaliar os resultados estatisticamente. Resultados: Os materiais com diferentes % de DPI apresentaram diferenças significativas para os testes de DC, FS e EM. A porcentagem em massa de 0% de DPI mostrou valores inferiores a todos os testados e os materiais com adição 2% apresentaram a melhor performance. Materiais com 0% e 2% de DPI apresentaram valores inferiores de WSp; a porcentagem de 0% proporcionou valores estatisticamente maiores para SI. Conclusão: Todos os materiais testados apresentaram pH semelhante nos eluatos independente do tempo de armazenamento, contudo, apenas os materiais com 2% e 4% mantiveram o pH dos eluatos estatisticamente similares nos tempos de estocagem de 72h a 7 dias.(AU)

Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp

Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.

An overview of preparation and characterization of solid binary system and its application on transdermal film with variation of plasticizers

Chemotherapy induced nausea and vomiting (CINV) and post-operative nausea and vomiting (PONV) is a problem, often occurs in patient. Inspite of high bioavailability, the demerits such as: hepatic first pass metabolism and invasive nature of oral and parenteral dosage forms can be avoided with anti-emetic therapy of transdermal device. The major objective of the present study is to modify the hydrochloride (HCl) form of Ondansetron (OND) to the base form followed by improvement of solubility and permeability of OND by employing solid dispersion (SD) loaded patches. Preformulation study, as observed, begins with an approach to enthuse solubility of OND by SD technique choosing different carriers. The choice of carriers was rationalized by phase solubility study. Several combinations of transdermal films were prepared with pure drug, carriers and SDs with plasticizer Ka values of OND-HPßCD binary system were found lower (54.43 to 187.57 M-1) than that of OND-PVP K-30 binary system (1156.77 to 12203.6 M-1). The drug content of SDs and patches were found satisfactory. Better permeation rate (236.48±3.66 µg/3.935 cm2) with promising flux enhancement (8.30 fold) was found with DBP loaded SD patch (P6*). Hence, enhancement of solubility and permeability of P6* ensures that it can successfully enhance the bioavailability

Inclusion complexes of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin with 2-hydroxypropyl-(-cyclodextrin: solubility and antimicrobial activity

The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-ß-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-ß-cyclodextrin at 37 oC. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.

Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.