Exploring Co-Amorphous Formulations Of Nevirapine: Insights From Computational, Thermal, And Solubility Analyses.

This study aimed to assess the formation of nevirapine (NVP) co-amorphs systems (CAM) with different co-formers (lamivudine-3TC, citric acid-CAc, and urea) through combined screening techniques as computational and thermal studies, solubility studies; in addition to develop and characterize suitable NVP-CAM. NVP-CAM were obtained using the quench-cooling method, and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and polarized light microscopy (PLM), in addition to in vitro dissolution in pH 6.8. The screening results indicated intermolecular interactions occurring between NVP and 3TC; NVP and CAc, where shifts in the melting temperature of NVP were verified. The presence of CAc impacted the NVP equilibrium solubility, due to hydrogen bonds. DSC thermograms evidenced the reduction and shifting of the endothermic peaks of NVP in the presence of its co-formers, suggesting partial miscibility of the compounds. Amorphization was proven by XRD and PLM assays. In vitro dissolution study exhibited a significant increase in solubility and dissolution efficiency of NVP-CAM compared to free NVP. Combined use of screening studies was useful for the development of stable and amorphous NVP-CAM, with increased NVP solubility, making CAM promising systems for combined antiretroviral therapy.

Exploring the Dissolution, Solid-state Properties, and Long-term Storage Stability of Cryoprotectant-free Fenbendazole Nanoparticles.

Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.9 ug/mL), which can compromise its dissolution rate and absorption. Thus, this work aimed to apply a nanotechnological approach to improve drug solubility and dissolution performance. Fenbendazole nanoparticles stabilized by different poloxamers were obtained by lyophilization without cryoprotectants. The behavior of the drug in the solid state was analyzed by X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The nanosystems were also evaluated for solubility and dissolution rate. A long-term stability evaluation was performed for three years at room temperature. The yields of the lyophilization ranged between 75 and 81% for each lot. The nanoparticles showed a submicron size (< 340 nm) and a low polydispersity depending on the stabilizer. The physicochemical properties of the prepared systems indicated a remarkable amorphization of the drug, which influenced its solubility and dissolution performance. The drug dissolution from both the fresh and aged nanosystems was significantly higher than that of the raw drug. In particular, nanoparticles prepared with poloxamer 407 showed no significant modifications in their particle size in three years of storage. Physical stability studies indicated that the obtained systems prepared with P188, P237, and P407 suffered certain recrystallization during long storage at 25 °C. These findings confirm that selected poloxamers exhibited an important effect in formulating fenbendazole nanosystems with improved dissolution.

Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment

We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studie

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.

Preformulation studies for the development of a microemulsion formulation from Ambrosia peruviana All, with anti-inflammatory effect

Abstract Natural products are considered an important source of the therapeutic arsenal currently available. Among these alternatives are the seeds of Ambrosia peruviana (altamisa), whose extract has shown an anti-inflammatory effect. The main objective of this work was to perform a preformulation study of Ambrosia peruviana seeds ethanolic extract, where the main factors that affect the physical, chemical, and pharmacological stability of the extract were evaluated, as well as a compatibility study by differential scanning calorimetry (DSC) analysis against different excipients. A dry extract was obtained by rotary evaporation of the seeds macerated with 96% ethanol. The anti-inflammatory activity was determined by measuring its effect on NO production in RAW 264.7 macrophages, stimulated with LPS. The results showed that the dry extract maintained its stability over time when stored at a temperature of 4 and 25ºC, demonstrating its biological activity, the content of phenolic compounds, and its physicochemical parameters remain practically invariable. However, when exposed to high temperatures (60 ºC) it was affected. The thermal analysis revelated that the behavior of most of the selected excipients and the dry extract was maintained, which indicates that it did not present incompatibilities, therefore they can be candidates for formulating a microemulsion.

Preparação e caracterização de nanocarreadores de beta-lactose à base de pectina e lisozima / Preparation and characterization of beta-lactose nanocarriers based on pectin and lysozyme

O objetivo deste trabalho foi preparar e caracterizar nanocarreadores via auto-organização a partir da pectina de citros e lisozima para o encapsulamento da ß-lactose. Foram estudadas três condições de interação entre os biopolímeros variando a razão molar pectina/lisozima (3:1, 2:1, 1:1, 1:2 e 1:3), o pH e o tempo de aquecimento. A confirmação da interação foi determinada por espectroscopia no infravermelho por transformada de Fourier (FTIR) e por calorimetria de varredura diferencial (DSC). Os espectros de infravermelho evidenciaram que ligações de hidrogênio foram as principais forças envolvidas na formação dos nanocarreadores e sugeriram a ausência de ß-lactose livre na superfície das nanopartículas. Os termogramas evidenciaram que as nanopartículas formadas na presença de ß-lactose têm maior estabilidade térmica do que as nanopartículas sem ß-lactose. Para ambas as formulações estudadas, na presença e na ausência de ß-lactose, a formação das nanopartículas ocorreu entre os valores de pKa e ponto isoelétrico (pI) da pectina e lisozima, respectivamente, sendo a melhor razão de interação pectina/lisozima 1:2, em pH 10, a 80 ºC por 30 min. As nanopartículas foram formadas via auto-organização e todos as partículas apresentaram distribuição de tamanho homogênea, formato esférico, diâmetro inferior a 100 nm e carga superficial negativa. A morfologia e o tamanho das partículas pouco alteraram com a incorporação da -lactose. A eficiência de encapsulação (EE) da ß-lactose foi superior a 96% para as concentrações estudadas. Ensaios preliminares in vitro, em células epiteliais de câncer de cólon (HCT-116), evidenciaram que as nanopartículas formadas são capazes de adentrar no meio intracelular, possivelmente, por via endocitose

This work aimed to prepare and characterize nanocarriers via self-assembly using citrus pectin and lysozyme for ß-lactose encapsulation. Three interaction conditions between the biopolymers were studied, varying the pectin/lysozyme molar ratio (3:1, 2:1, 1:1, 1:2 and 1:3), pH and heating time. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) determined the interaction's confirmation. The infrared spectra showed that hydrogen bonds were the main forces involved in the formation of nanocarriers and suggested the absence of free ß-lactose on the surface of the nanoparticles. The thermograms showed that nanoparticles formed in the presence of ß-lactose have greater thermal stability than nanoparticles without ß-lactose. For both formulations studied, in the presence and absence of lactose, the formation of nanoparticles occurred between the pKa and isoelectric point (pI) values of pectin and lysozyme, respectively, with the best pectin/lysozyme interaction molar ratio 1:2, at pH 10, at 80 °C for 30 min. Nanoparticles were formed via self-assembly, and all particles presented homogeneous size distribution, spherical shape, diameter less than 100 nm, and negative surface charge. The morphology and size of the particles changed little with the incorporation of ß-lactose. The encapsulation efficiency (EE) of ß-lactose was higher than 96% for the concentrations studied. Preliminary in vitro assays in colon cancer epithelial cells (HCT-116) showed that the nanoparticles formed are capable of entering the intracellular medium, possibly via endocytosis

Curcumin solid dispersion based on three model acrylic polymers: formulation and release properties

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Physicochemical characterization and cosmetic applications of Passiflora nitida Kunth leaf extract

Abstract Passiflora nitida Kunth, an Amazonian Passiflora species, is little studied, although the specie's high biological potential. Herein the plant's pharmacognostic characterization, extract production, antioxidant potential evaluation, and application of this extract in cosmetic products is reported. The physical chemical parameters analyzed were particle size by sieve analysis, loss through drying, extractive yield, total ash content, laser granulometry, specific surface area and pore diameter (SBET), differential scanning calorimetry, thermogravimetry (TG), and wave dispersive X-Ray fluorescence (WDXRF). Total phenol/flavonoid content, LC-MS/MS analysis, DPPH and ABTS antioxidant radical assays, cytotoxicity, melanin, and tyrosinase inhibition in melanocytes test provided evidence to determine the content of the major constituent. P. nitida dry extract provided a fine powder with mesopores determined by SBET, with the TG curve showing five stages of mass loss. The antioxidant potential ranged between 23.5-31.5 mg∙mL-1 and tyrosinase inhibition between 400-654 µg∙mL-1. The species presented an antimelanogenic effect and an inhibitory activity of cellular tyrosinase (26.6%) at 25 µg/mL. The LC-MS/MS analysis of the spray-dried extract displayed the main and minor phenolic compounds constituting this sample. The results indicate that P. nitida extract has promising features for the development of cosmetic formulations

Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

Abstract The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612)

Radiation-induced graft polymerization of elastin onto polyvinylpyrrolidone as a possible wound dressing.

The purpose of our study was to obtain new wound dressings in the form of hydrogels that promote wound healing taking advantage of the broad activities of elastin (ELT) in physiological processes. The hydrogel of ELT and polyvinylpyrrolidone (PVP; ELT-PVP) was obtained by cross-linking induced by gamma irradiation at a dose of 25 kGy. The physicochemical changes attributed to cross-linking were analyzed through scanning electron microscopy (SEM), infrared spectroscopy analysis with Fourier transform (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Furthermore, we performed a rheological study to determine the possible changes in the fluidic macroscopic properties produced by the cross-linking method. Finally, we accomplished viability and proliferation analyses of human dermal fibroblasts in the presence of the hydrogel to evaluate its biological characteristics. The hydrogel exhibited a porous morphology, showing interconnected porous with an average pore size of 16 ± 8.42 µm. The analysis of FTIR, DSC, and TGA revealed changes in the chemical structure of the ELT-PVP hydrogel after the irradiation process. Also, the hydrogel exhibited a rheological behavior of a pseudoplastic and thixotropic fluid. The hydrogel was biocompatible, demonstrating high cell viability, whereas ELT presented low biocompatibility at high concentrations. In summary, the hydrogel obtained by gamma irradiation revealed the appropriate morphology to be applied as a wound dressing. Interestingly, the hydrogel exhibited a higher percentage of cell viability compared with ELT, suggesting that the cross-linking of ELT with PVP is a suitable strategy for biological applications of ELT without generating cellular damage.

Influence of gelatinization degree and octenyl succinic anhydride esterification on the water sorption characteristics of corn starch.

The effects of gelatinization degree (GD) and octenyl succinic anhydride (OSA) esterification in the sorption-desorption characteristics of normal corn starch (NCS) were studied. NCS was subjected to different GD (53, 70, and 96%) with an extruder and lyophilized. FTIR analysis revealed that GD increased the hydrated (995/1022 ratio) and decreased the short-range ordered (1022/1047 ratio). The equilibrium sorption-desorption curve of starches was obtained for water activities up to 0.95 and fitted with the Guggenheim-Anderson-de Boer (GAB) model. Gelatinization of corn starch decreased its water sorption capacity, increased its sorption hysteresis and decreased its monolayer moisture content. OSA treatment of NCS reduced the water sorption capacity, hysteresis, and monolayer moisture content as reflected by slight variations of these parameters with the GD. A principal component analysis showed that GD and OSA esterification are mutually independent treatments, which can provide different effects on the water sorption characteristics of NCS.

Avaliação do desempenho de oleogéis estruturados com ceras vegetais como base lipídica reduzida em ácidos graxos saturados aplicados em cream cheeses / Performance evaluation of structured oleogels with vegetable waxes as a reduced lipid base in saturated fatty acids applied in cream cheeses

Diante das exigências crescentes das agências regulatórias do mundo todo quanto à redução/eliminação de ácidos graxos trans nos alimentos industrializados, bem como da conscientização do consumidor sobre a relação entre alimentação e saúde, o desenvolvimento de alternativas mais saudáveis aos óleos parcialmente hidrogenados e a outras fontes lipídicas com alto grau de saturaçã o se faz necessário. O oleogel, um sistema composto por um óleo preso em uma rede tridimensional formada por um agente estruturante, se apresenta como uma solução promissora. Dentre os diversos agentes estruturantes, as ceras vegetais se destacam por sua excelente capacidade de gelificação de óleos. Contudo, apresentam uma desvantagem sob o aspecto sensorial, pois podem conferir cerosidade e sabor residual desagradável aos alimentos. Com o objetivo de viabilizar o uso das ceras como agentes estruturantes em oleogéis face ao seu excelente desempenho tecnológico, este projeto propõe o estudo e a aplicação de oleogéis à base de óleo de soja (SBO) estruturado com ceras de farelo de arroz (RBW) a 2 e 4 % (m/m) ou carnaúba (CBW) a 3 e 6% (m/m), isoladamente. As matérias-primas foram caracterizadas e o comportamento de gelificação de cada cera foi avaliado por análises de textura por penetração de cone, estabilidade à perda de óleo por centrifugação, energia coesiva por parâmetro de solubilidade de Hansen (HSP) e comportamento de cristalização e fusão por calorimetria exploratória diferencial (DSC). Os resultados mostraram que ambas as ceras são capazes de formar oleogéis estruturalmente estáveis, contudo, o oleogel com 2% de RBW apresentou maior firmeza a 20 °C (190,4 gf/cm2) do que o oleogel com 6% de CBW a 5 °C (186,1 gf/cm2). Ao final de 5 dias, a capacidade de retenção de óleo do oleogel preparado com RBW foi de 100% às concentrações de 2 e 4% (m/m), contra 61 e 99,3% do oleogel elaborado com CBW às concentrações de 3 e 6% (m/m), respectivamente. Esses resultados podem ser explicados pela diferença entre as energias coesivas, ou seja, do grau de interação molecular entre o solvente e o soluto de cada oleogel. De acordo com os resultados de distância, que prevê se o gel formado será forte, fraco ou se não haverá formação de gel, o soluto CBW apresentou menor interação com o óleo (3,3 MPa1/2) do que o soluto RBW (3,7 MPa1/2). Os oleogéis foram aplicados como ingredientes em diferentes formulações de cream cheese, que foram analisados quanto a diferentes parâmetros de textura e esses resultados foram comparados a uma referência comercial. Nenhuma das amostras produzidas obteve resultados de textura estatisticamente iguais aos do cream cheese comercial (CC), o que pode ser explicado pelas diferenças de formulação e processamento dos produtos. Face aos resultados para textura e estabilidade à perda de óleo dos oleogéis de RBW, este agente estruturante apresenta ria maior potencial de aplicação, porém o oleogel CBW6 obteve alta capacidade de retenção de óleo (99,3%) e quando aplicado na formulação de cream cheese (CCBW6) apresentou resultados de firmeza e espalhabilidade mais próximos da amostra de referência, feita com gordura do leite (CMF)

Given the growing demands of regulatory agencies around the world regarding the reduction/elimination of trans fatty acids in processed foods, as well as consumer awareness about the relationship between food and health, the development of healthier alternatives to partially hydrogenated oils and others lipid sources with a high degree of saturation are necessary. Oleogel, a system composed of an oil trapped in a three-dimensional network formed by a structuring agent, presents itself as a promising solution. Among the various structuring agents, vegetable waxes stand out for their excellent oil gelling capacity. However, they have a sensory disadvantage, as they can give waxy and unpleasant aftertaste to foods. Aiming at enabling the use of waxes as structuring agents in oleogels in view of their excellent technological performance, this study proposes the evaluation and application of oleogels based on soybean oil (SBO) structured with rice bran wax (RBW) at 2 and 4% (m/m) or carnauba (CBW) at 3 and 6% (m/m). The raw materials were characterized and the gelling behavior of each wax was evaluated by analysis of texture by cone penetration, stability to oil loss by centrifugation, cohesive energy by Hansen solubility parameter (HSP) and crystallization and melting behavior. by differential scanning calorimetry (DSC). The results showed that both waxes are able to form structurally stable oleogels, however, oleogel with 2% RBW showed greater firmness at 20 °C (190.4 gf/cm2) than oleogel with 6% CBW at 5° C (186.1 gf/cm2). At the end of 5 days, the oil retention capacity of oleogel prepared with RBW was 100% at concentrations of 2 and 4% (m/m), against 61 and 99.3% of oleogel prepared with CBW at concentrations of 3 and 6% (m/m), respectively. These results can be explained by the difference between the cohesive energies, that is, the degree of molecular interaction between the solvent and the solute of each oleogel. According to the distance results, which predicts if the formed gel will be strong, weak or if there will be no gel formation, the CBW solute showed less interaction with the oil (3.3 MPa1/2) than the RBW solute (3 ,7 MPa1/2). Oleogels were applied as ingredients in different cream cheese formulations, which were analyzed for different texture parameters and these results were compared to a commercial reference. None of the samples produced had texture results statistically equal to those of commercial cream cheese (CC), which can be explained by the differences in formulation and processing of the products. Given the results for texture and oil binding capacity of RBW oleogels, this structuring agent would present greater application potential, but CBW6 oleogel obtained high oil biding capacity (99.3%) and when applied in cream cheese formulation (CCBW6) showed firmness and spreadability results closer to the reference sample, made with milk fat (CMF)

Desenvolvimento e caracterização de dispersões sólidas de efavirenz / Development and characterization of efavirenz solid dispersions

A baixa solubilidade aquosa dos insumos farmacêuticos ativos (IFA) é um grande desafio no desenvolvimento de formulações farmacêuticas, pois pode resultar em biodisponibilidade insuficiente e variável. Diversas estratégias de modificação do estado sólido dos compostos ativos, têm sido propostas para incrementar a solubilidade de fármacos pouco solúveis em água. Dentre as estratégias abordadas a ispersão sólida (DS) é uma das formas mais promissoras de aumentar a solubilidade, dissolução e a biodisponibilidade de IFAs com baixa solubilidade aquosa. O efavirenz (EFV) é um inibidor não nucleosídeo da transcriptase reversa (NNRTI) e um dos componentes da terapia antirretroviral de alta atividade (HAART), sendo parte da primeira linha de tratamento de infecções do vírus HIV tipo 1. O antirretroviral está classificado como pertencente à classe II do SCB, e exibe baixa solubilidade aquosa (solubilidade menor que 10 µg/mL) e alta permeabilidade com absorção dependente da taxa de dissolução, resultando em biodisponibilidade oral baixa e variável. A administração de fármacos pouco solúveis na forma de DS é um método atraente para aumentar a biodisponibilidade in vivo. Neste estudo, um método de triagem rápida por evaporação de solvente foi empregado para preparar DS de EFV, variando-se proporções em misturas compostas pelos carreadores, polivinilpirrolidona K-28/32 (PVP K-28/32), copovidona (CoPVP), hidroxipropilmetilcelulose ftalato (HPMCP-50, HPMCP-55 e HPMCP-55s), poloxâmero 188 (P188) e poloxâmero 407 (P407). A solubilidade das DS foi avaliada por meio do método do equilíbrio (shake-flask), onde selecionou-se os polímeros P188 e P407 que conduziram a uma elevada capacidade de saturação em meio aquoso, superior a 1.000 vezes ao fármaco puro. As propriedades físico-químicas e do estado sólido das amostras foram avaliadas por meio de calorimetria exploratória diferencial (DSC); termogravimetria (TG); espectroscopia do infravermelho com transformada de Fourier (FTIR), difratometria de raios X pelo método do pó (DRXP) e ensaios de dissolução com emprego do aparato IV USP. Os resultados de DRXP demonstraram que os carreadores P188 e P407 foram capazes de estabilizar o EFV na forma amorfa nas DS, fato esse evidenciado pela ausência de picos característicos do antirretroviral

he low aqueous solubility of the active pharmaceutical ingredient (API) is a major challenge in the development of pharmaceutical formulations as it may result in insufficient and variable bioavailability. Several strategies for modifying the solid-state of the active compounds have been proposed to increase solubility of drugs that are poorly soluble in water. Among the strategies approaches, solid dispersion (SD) is one of the most promising ways to increase solubility, dissolution and bioavailability of APIs with low aqueous solubility. Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and one of the components of highly active antiretroviral therapy (HAART), being part of the first line of treatment of type 1 HIV virus infections. The antiretroviral is classified as belonging to BCS class II, and exhibits low aqueous solubility (solubility less than 10 µg / mL) and high permeability with dissolution ratedependent absorption, resulting in low and variable oral bioavailability. Drug delivery of poorly aqueous soluble drugs in form SD is an appealing method to increase in vivo bioavailability. In this study, a fast screening method of solvent evaporation method was used to prepare EFV SD, varying the proportions in mixtures composed by the carriers polyvinylpyrrolidone K-28/32 (PVP K-28/32), copovidone (CoPVP), hydroxypropylmethylcellulose phthalate (HPMCP-50, HPMCP-55 e HPMCP-55s), poloxamer 188 (P188) e poloxamer 407 (P407). The solubility of the samples was evaluated by the method of equilibrium (shake-flask), wherein the polymers P188 and P407 were selected due to the capacity to promote high saturation in aqueous medium, 1,000 times superior to the pure drug. The physicochemical and solid-state properties of the samples were evaluated by differential scanning calorimetry (DSC); thermogravimetry (TG); Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD) and dissolution assays using the IV USP apparatus. The results of XRPD demonstrated that the carriers P188 and P407 were able to stabilize the EFV in amorphous form in the SD, a fact evidenced by the absence of characteristic peaks of the antiretroviral

Raman Spectroscopy Studies on the Barocaloric Hybrid Perovskite [(CH3)4N][Cd(N3)3].

Temperature-dependent Raman scattering and differential scanning calorimetry were applied to the study of the hybrid organic-inorganic azide-perovskite [(CH3)4N][Cd(N3)3], a compound with multiple structural phase transitions as a function of temperature. A significant entropy variation was observed associated to such phase transitions, |∆S| ~ 62.09 J·kg-1 K-1, together with both a positive high barocaloric (BC) coefficient |δTt/δP| ~ 12.39 K kbar-1 and an inverse barocaloric (BC) coefficient |δTt/δP| ~ -6.52 kbar-1, features that render this compound interesting for barocaloric applications. As for the obtained Raman spectra, they revealed that molecular vibrations associated to the NC4, N3- and CH3 molecular groups exhibit clear anomalies during the phase transitions, which include splits and discontinuity in the phonon wavenumber and lifetime. Furthermore, variation of the TMA+ and N3- modes with temperature revealed that while some modes follow the conventional red shift upon heating, others exhibit an unconventional blue shift, a result which was related to the weakening of the intermolecular interactions between the TMA (tetramethylammonium) cations and the azide ligands and the concomitant strengthening of the intramolecular bondings. Therefore, these studies show that Raman spectroscopy is a powerful tool to gain information about phase transitions, structures and intermolecular interactions between the A-cation and the framework, even in complex hybrid organic-inorganic perovskites with highly disordered phases.

Synthesis and Characterization of Nanostructured Lipid Nanocarriers for Enhanced Sun Protection Factor of Octyl p-methoxycinnamate.

Sunlight is important to health, but higher exposure to radiation causes early aging of the skin and skin damage that can lead to skin cancers. This study aimed at producing a stable octyl p-methoxycinnamate (OMC)-loaded nanostructured lipid carrier (NLC) sunscreen, which can help in the photoprotective effect. NLC was produced by emulsification-sonication method and these systems were composed of myristyl myristate (MM), caprylic capric triglyceride (CCT), Tween® 80 (TW), and soybean phosphatidylcholine (SP) and characterized by dynamic light scattering (DLS), zeta potential (ZP) measurement, atomic force microscopy (AFM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and in vitro release studies. Pre-formulation studies were performed changing TW concentrations and no differences were found at concentrations of 1.0 and 2.0%. Two selected formulations were designed and showed an average size of 91.5-131.7, polydispersity index > 0.2, and a negative value of ZP. AFM presented a sphere-like morphology and SEM showed ability to form a thin film. DSC exhibited that the incorporation of OMC promoted reduction of enthalpy due to formation of a more amorphous structure. Drug release shows up to 55.74% and 30.57%, and this difference could be related to the presence of SP in this formulation that promoted a more amorphous structure; the release mechanism study indicated Fickian diffusion and relaxation. Sun protection factor (SPF) evaluation was performed using NLC and presented values around 40, considerably higher than those observed in the literature. The developed formulations provide a beneficial alternative to conventional sunscreen formulations.

Synthesis, Characterization, and Histological Evaluation of Chitosan-Ruta Graveolens Essential Oil Films.

The development of new biocompatible materials for application in the replacement of deteriorated tissues (due to accidents and diseases) has gained a lot of attention due to the high demand around the world. Tissue engineering offers multiple options from biocompatible materials with easy resorption. Chitosan (CS) is a biopolymer derived from chitin, the second most abundant polysaccharide in nature, which has been highly used for cell regeneration applications. In this work, CS films and Ruta graveolens essential oil (RGEO) were incorporated to obtain porous and resorbable materials, which did not generate allergic reactions. An oil-free formulation (F1: CS) and three different formulations containing R. graveolens essential oil were prepared (F2: CS-RGEO 0.5%; F3: CS+RGEO 1.0%; and F4: CS+RGEO 1.5%) to evaluate the effect of the RGEO incorporation in the mechanical and thermal stability of the films. Infrared spectroscopy (FTIR) analyses demonstrated the presence of RGEO. In contrast, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis showed that the crystalline structure and percentage of CS were slightly affected by the RGEO incorporation. Interesting saturation phenomena were observed for mechanical and water permeability tests when RGEO was incorporated at higher than 0.5% (v/v). The results of subdermal implantation after 30 days in Wistar rats showed that increasing the amount of RGEO resulted in greater resorption of the material, but also more significant inflammation of the tissue surrounding the materials. On the other hand, the thermal analysis showed that the RGEO incorporation almost did not affect thermal degradation. However, mechanical properties demonstrated an understandable loss of tensile strength and Young's modulus for F3 and F4. However, given the volatility of the RGEO, it was possible to generate a slightly porous structure, as can be seen in the microstructure analysis of the surface and the cross-section of the films. The cytotoxicity analysis of the CS+RGEO compositions by the hemolysis technique agreed with in vivo results of the low toxicity observed. All these results demonstrate that films including crude essential oil have great application potential in the biomedical field.

Interactions of amphipathic α-helical MEG proteins from Schistosomamansoni with membranes.

Micro Exon Gene (MEG) proteins are thought to play major roles in the infection and survival of parasitic Schistosoma mansoni worms in host organisms. Here, the physical chemical properties of two small MEG proteins found in the genome of S. mansoni, named MEG-24 and MEG-27, were examined by a combination of biophysical techniques such as differential scanning calorimetry, tensiometry, circular dichroism, fluorescence, and electron spin resonance spectroscopies. The proteins are surface active and structurally arranged as cationic amphipathic α-helices that can associate with lipid membranes and cause their disruption. Upon adsorption to lipid membranes, MEG-27 strongly affects the fluidity of erythrocyte ghost membranes, whereas MEG-24 forms pores in erythrocytes without modifying the ghost membrane fluidity. Whole-mount in situ hybridization experiments indicates that MEG-27 and MEG-24 transcripts are located in the parasite esophagus and subtegumental cells, respectively, suggesting a relevant role of these proteins in the host-parasite interface. Taken together, these characteristics lead us to propose that these MEG proteins may interact with host cell membranes and potentially modulate the immune process using a similar mechanism as that described for α-helical membrane-active peptides.

Formulation and evaluation of a mucoadhesive buccal tablet of mefenamic acid

Buccal route of administration has many advantages such as improving patient compliance, bypassing the GIT and hepatic first pass effect. The objectives are to formulate mucoadhesive buccal tablet using Mefenamic acid and compatible excipients, and to evaluate the product using quality control tests and in vitro tests. The ingredients were subjected to Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy studies for compatibility test and the results showed no interaction. Two batches of mefenamic buccal tablet were prepared. The tablet thickness and diameter are 3.75 mm and 12 mm respectively. All tablets are within the specification of +/- 5%. The in-house tablet hardness is 6.8-15kg and percent friabilation is not more than 0.8%. The disintegration test showed that all tablets disintegrated within 4 hours. The content uniformity showed that tablets are within the range of 85%-115%. The tablet weight is within the 5% range. The percent swelling is 53.83% to 58.86% and moisture absorption is 14.79% to 15.56%. The surface pH of the tablet is close to the salivary pH, which means that it would not irritate the buccal mucosa. The buccal tablet has a mucoadhesiveness of 0.196 to 0.200. There was no change in pH and size after subjecting it to stability studies in human saliva. Drug release studies showed 80.7% to 83.4% after 3 hours. Even after 3 months of subjecting the tablets to 40 ºC and 75% RH, results are within acceptable range. The results show the potential of the formulation as a mucoadhesive buccal tablet.

Polymer blend: a new approach for eliminating curing effect of aqueous dispersion coatings

The aim of present work was to investigate blends of Eudragit® NE 30D with Aquacoat® ECD using different ratios to eliminate curing effect associated with individual polymers. Propranolol HCl 10% w/w was layered onto sugar cores using 5% w/w HPMC as a binder. Drug-layered-cores were coated either with pure or blends of Aquacoat® ECD: Eudragit® NE 30D in a fluidized bed coater to obtain 20% w/w coating level. Talc 35% w/w was used as anti-tacking agent. The pellets were characterized for in vitro dissolution studies, morphology, water uptake-weight loss, osmolality and adhesion of coating after curing at 60 °C or 60 °C/75% RH for 24 h. The findings revealed that Aquacoat® ECD coated pellets showed curing effect due to further gradual coalescence of polymeric particles which resulted into better film formation upon curing. In contrast, the curing effect of Eudragit® NE 30D coated pellets was caused by decrease in adhesion of coatings after curing which provided entirely different swelling behavior of uncured (localized swelling) and cured (uniform swelling) pellets. The undesired curing effect of individual polymers was eliminated by using their blends in appropriate ratio.

Controlled release alginate-chitosan microspheres of tolmetin sodium prepared by internal gelation technique and characterized by response surface modeling

Tolmetin sodium (TS) is a powerful non-steroidal mitigating drug for the treatment of rheumatoid joint inflammation, osteoarthritis, and adolescent rheumatoid joint pain. In addition to its gastrointestinal (GIT) problems, TS has a short biological half-life (1 hr). In a trial to overcome these side effects and control the rate of (TS) release, chitosan coated alginate microspheres are recommended. A Box-Behnken experimental design was employed to produce controlled release microspheres of TS in the sodium alginate and chitosan copolymers (Alg-Ch) by emulsification internal gelation methodology. The effect of critical formulation variables namely, drug to polymer ratio (D:P ratio), speed of rotation and span 80% on drug encapsulation efficiency (% EE), drug release at the end of 2 hours (Rel2) and drug release at the end of 8 hours (Rel8) were analyzed using response surface modeling. The parameters were assessed using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis. The produced microspheres were spherical in shape with extensive pores at D:P ratio 1:1 and small pores at a drug to polymer ratio (D:P ratio) 1:3. Differential scanning calorimetry (DSC) affirmed the steady character of TS in microspheres and revealed their crystalline form. All formulation variables examined exerted a significant influence on the drug release, whereas the speed emerged as a lone factor significantly influencing % EE. Increasing the D: P ratio decreases the release of the drug after two and 8 hours. The increase in speed results in an increase in drug release after two and eight hours. The drug release from the microspheres followed zero order kinetics. TS Alg-Ch microspheres exhibited a significant anti-inflammatory effect on incited rat paw edema after eight hours. These results revealed that the internal gelation technique is a promising method to control TS release and eradicate GIT side effects using Alg-Ch copolymers.