Evaluating the application of an arabinoxylan-rich fraction from brewers' spent grain as a release modifier of drugs.

This study evaluated the possible use of a fraction of brewers' spent grain rich in arabinoxylans (BSG-AX) as an excipient that modifies the release of class III drugs (Biopharmaceutics Classification System), by determining the release profile of metformin hydrochloride (MH), in a water medium. The cumulative percentage of MH release showed the best linear fit when modeled with the cumulative distribution function (CDF) of the Weibull distribution (R2 = 0.993 ± 0.001). According to the Korsmeyer-Peppas model, the first stage of MH release is regulated by a super case-II transport mechanism controlled by the expansion and relaxation of BSG-AX. Finally, with the Hixson-Crowell model, a release rate (kHC) of 0.350 ± 0.026 h-13 was obtained (R2 = 0.996 ± 0.007). BSG-AX constitutes a suitable material for producing prolonged drug release vehicles; however, additional research is required to provide a better encapsulation of the active ingredients to ensure their optimal applicability and performance.

Investigation into Brazilian Palygorskite for Its Potential Use as Pharmaceutical Excipient: Perspectives and Applications.

Palygorskite is an aluminum and magnesium silicate characterized by its fibrous morphology, providing it with great versatility in industrial applications, including pharmaceuticals. Although most of the reserves are in the United States, in recent years occurrences of commercially exploited deposits in Brazil have been recorded, mainly in the country's northeast region. This has motivated this study, which analyzes raw Brazilian palygorskite compared to a commercial sample (Pharmasorb® colloidal) to demonstrate its pharmaceutical potential. The chemical and mineral composition of the samples were evaluated for surface properties, granulometry, morphology, crystallography, thermal analysis, and spectroscopy. Raw palygorskite presented 67% purity, against 74% for Pharmasorb® colloidal. The percentage purity relates to the presence of contaminants, mainly carbonates and quartz (harmless under conventional conditions of pharmaceutical use). Furthermore, it was possible to confirm the chemical composition of these phyllosilicates, formed primarily of silicon, aluminum, and magnesium oxides. The crystallographic and spectroscopic profiles were consistent in both samples, showing characteristic peaks for palygorskite (2θ = 8.3°) and bands attributed to fibrous phyllosilicates below 1200 cm-1, respectively. The thermal analysis allowed the identification of the main events of palygorskite, with slight differences between the evaluated samples: loss of water adsorbed onto the surface (~85 °C), removal of water contained in the channels (~200 °C), coordinated water loss (~475 °C), and, finally, the dehydroxylation (>620 °C). The physicochemical characteristics of raw palygorskite align with pharmacopeial specifications, exhibiting a high specific surface area (122 m2/g), moderately negative charge (-13.1 mV), and compliance with the required limits for heavy metals and arsenic. These favorable technical attributes indicate promising prospects for its use as a pharmaceutical ingredient in the production of medicines and cosmetics.

Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method: challenges and opportunities for process optimization through quality by design approach.

The freeze-thaw (F/T) method is commonly employed during the processing and handling of drug substances to enhance their chemical and physical stability and obtain pharmaceutical applications such as hydrogels, emulsions, and nanosystems (e.g., supramolecular complexes of cyclodextrins and liposomes). Using F/T in manufacturing hydrogels successfully prevents the need for toxic cross-linking agents; moreover, their use promotes a concentrated product and better stability in emulsions. However, the use of F/T in these applications is limited by their characteristics (e.g., porosity, flexibility, swelling capacity, drug loading, and drug release capacity), which depend on the optimization of process conditions and the kind and ratio of polymers, temperature, time, and the number of cycles that involve high physical stress that could change properties associated to quality attributes. Therefore, is necessary the optimization of F/T conditions and variables. The current research regarding F/T is focused on enhancing the formulations, the process, and the use of this method in pharmaceutical, clinical, and biological areas. The present review aims to discuss different studies related to the impact and effects of the F/T process on the physical, mechanical, and chemical properties (porosity, swelling capacity) of diverse pharmaceutical applications with an emphasis on their formulation properties, the method and variables used, as well as challenges and opportunities in developing. Finally, we review the experimental approach for choosing the standard variables studied in the F/T method applying the systematic methodology of quality by design.

Biotechnological Applications of Nanoencapsulated Essential Oils: A Review.

Essential oils (EOs) are complex mixtures of volatile and semi-volatile organic compounds that originate from different plant tissues, including flowers, buds, leaves and bark. According to their chemical composition, EOs have a characteristic aroma and present a wide spectrum of applications, namely in the food, agricultural, environmental, cosmetic and pharmaceutical sectors. These applications are mainly due to their biological properties. However, EOs are unstable and easily degradable if not protected from external factors such as oxidation, heat and light. Therefore, there is growing interest in the encapsulation of EOs, since polymeric nanocarriers serve as a barrier between the oil and the environment. In this context, nanoencapsulation seems to be an interesting approach as it not only prevents the exposure and degradation of EOs and their bioactive constituents by creating a physical barrier, but it also facilitates their controlled release, thus resulting in greater bioavailability and efficiency. In this review, we focused on selecting recent articles whose objective concerned the nanoencapsulation of essential oils from different plant species and highlighted their chemical constituents and their potential biotechnological applications. We also present the fundamentals of the most commonly used encapsulation methods, and the biopolymer carriers that are suitable for encapsulating EOs.

Three-Dimensional Printing Technologies for Drug Delivery Applications: Processes, Materials, and Effects.

Since the 1930s, new methods of drug delivery, such as implantable devices with drug release control, have been developed. However, manufacturing techniques require bulk due to high initial production costs. Three-dimensional (3D) printing, also known as additive manufacturing or rapid prototyping, allows the fabrication of personalized drug delivery that uses different materials and complex geometries with multiple release profiles, thereby eradicating high initial costs. Different studies have been developed showing the extensive potential of 3D printing for the pharmaceutical industry, and despite in-depth discussions that have been published, there is no comprehensive review of processes, materials, and effects in drug delivery applications thus far. This review aims to fill this gap by presenting the use of 3D printing technology for drug delivery, exposing the different variations of the technique according to the characteristics, material, and dosage form sought. There are seven main categories of 3D printing according to the standards jointly developed by International Organization for Standardization and American Society for Testing and Materials: material jetting, binder jetting, material extrusion, vat photopolymerization, powder bed fusion, sheet lamination, and directed energy deposition. There are different 3D fabrication processes used for drug delivery applications depending on the dosage form and material applied. In this context, polymers, glasses, and hydrogels represent the most frequent materials used. 3D printing allows different forms of drug dosage. Oral, topical, rectal and vaginal, parental and implantable are discussed in this paper, presenting the identification of the type of 3D printing technology, the active pharmaceutical ingredient, formulation, and pharmaceutical effect. The main aim of this paper is to offer insights to people from academy and industry who are interested in the advancement of drug delivery and in knowing the future directions in the development of 3D printing applications in this area.

An Updated Review of Macro, Micro, and Nanostructured Hydrogels for Biomedical and Pharmaceutical Applications.

Hydrogels are materials with wide applications in several fields, including the biomedical and pharmaceutical industries. Their properties such as the capacity of absorbing great amounts of aqueous solutions without losing shape and mechanical properties, as well as loading drugs of different nature, including hydrophobic ones and biomolecules, give an idea of their versatility and promising demand. As they have been explored in a great number of studies for years, many routes of synthesis have been developed, especially for chemical/permanent hydrogels. In the same way, stimuli-responsive hydrogels, also known as intelligent materials, have been explored too, enhancing the regulation of properties such as targeting and drug release. By controlling the particle size, hydrogel on the micro- and nanoscale have been studied likewise and have increased, even more, the possibilities for applications of the so-called XXI century materials. In this paper, we aimed to produce an overview of the recent studies concerning methods of synthesis, biomedical, and pharmaceutical applications of macro-, micro, and nanogels.

Paramylon and synthesis of its ionic derivatives: Applications as pharmaceutical tablet disintegrants and as colloid flocculants.

Paramylon, a high molecular weight polysaccharide, is a linear and unbranched (1 → 3)-ß-d-glucan. Despite its numerous biological benefits, the poor aqueous solubility of crystalline paramylon is a drawback that has hampered some of its applications. In an effort to make this biomaterial amenable to practical uses, cationic and anionic paramylon derivatives were obtained. The degrees of substitution of both products were determined. The products were characterized by FT-IR spectrocopy, ESI mass spectrometry, 1H, 13C and 1H-13C NMR and SEM microscopy. These techniques confirmed the success of the substitution reactions. 1H NMR analysis was used to develop alternative methods for an approximate estimation of the degree of substitution. 1H-13C HSQC NMR spectra were assigned for both derivatives. New applications of native, cationic and anionic paramylon were found. Native paramylon showed similar performance as pharmaceutical tablet disintegrant than sodium croscarmellose. Cationic paramylon behavior as colloid flocculant was comparable with commercial cationic polyacrylamides. The anionic derivative could eventually be used in the formulation of matrix controlled release systems or as a suspending agent.

Effect of Chitosan Dispersion and Microparticles on Older Streptococcus mutans Biofilms.

(1) Background: The effectiveness of chitosan to improve the action of antimicrobial compounds against planktonic bacteria and young biofilms has been widely investigated in Dentistry, where the biofilm lifecycle is a determining factor for the success of antibacterial treatment. In the present study, mature Streptococcus mutans biofilms were treated with chitosan dispersion (CD) or chitosan microparticles (CM). (2) Methods: CD at 0.25% and 1% were characterized by texture analysis, while CD at 2% was spray-dried to form CM, which were characterized with respect to particle size distribution, zeta potential, and morphology. After determining the minimum inhibitory and bactericidal concentrations, S. mutans biofilms were grown on glass slides exposed 8×/day to 10% sucrose and 2×/day to CD or CM at 0.25% and 1%. Biofilm viability and acidogenicity were determined, using appropriate control groups for each experiment. (3) Results: CD had high viscosity and CM were spherical, with narrow size distribution and positive zeta potential. CM affected bacterial viability and acidogenicity in mature S. mutans biofilms more strongly than CD, especially at 1%. (4) Conclusions: Both chitosan forms exerted antimicrobial effect against mature S. mutans biofilms. CM at 1% can reduce bacterial viability and acidogenicity more effectively than CD at 1%, and thereby be more effective to control the growth of mature biofilms in vitro.

Polymeric mixed micelles as nanomedicines: Achievements and perspectives.

During the past few decades, polymeric micelles have raised special attention as novel nano-sized drug delivery systems for optimizing the treatment and diagnosis of numerous diseases. These nanocarriers exhibit several in vitro and in vivo advantages as well as increased stability and solubility to hydrophobic drugs. An interesting approach for optimizing these properties and overcoming some of their disadvantages is the combination of two or more polymers in order to assemble polymeric mixed micelles. This review article gives an overview on the current state of the art of several mixed micellar formulations as nanocarriers for drugs and imaging probes, evaluating their ongoing status (preclinical or clinical stage), with special emphasis on type of copolymers, physicochemical properties, in vivo progress achieved so far and toxicity profiles. Besides, the present article presents relevant research outcomes about polymeric mixed micelles as better drug delivery systems, when compared to polymeric pristine micelles. The reported data clearly illustrates the promise of these nanovehicles reaching clinical stages in the near future.

Dendrimer Prodrugs.

The main objective of this review is to describe the importance of dendrimer prodrugs in the design of new drugs, presenting numerous applications of these nanocomposites in the pharmaceutical field. Therefore, the use of dendrimer prodrugs as carrier for drug delivery, to improve pharmacokinetic properties of prototype, to promote drug sustained-release, to increase selectivity and, consequently, to decrease toxicity, are just some examples of topics that have been extensively reported in the literature, especially in the last decade. The examples discussed here give a panel of the growing interest dendrimer prodrugs have been evoking in the scientific community.

Dendritic surface functionalization of nanomaterials: controlling properties and functions for biomedical applications

A wide variety of nanomaterials have demonstrated promise in medical applications such as drug delivery and imaging. In these applications, the surface chemistry of the materials is critical as it plays an important role in determining the toxicity and biodistribution behavior of the material. We review here the functionalization of nanomaterials with dendrons as an efficient method to alter the surface chemistry of the materials, introducing new properties and functions. Described here is the functionalization of superparamagnetic iron oxide nanoparticles (SPIO) with dendritic guanidines to enhance their transport into cells for magnetic resonance imaging applications. The introduction of dendrons bearing peripheral hydroxyls, amines, guanidines, carbohydrates and Gd(III) chelates to polymer vesicles (polymersomes) is also described. These dendritic moieties allow for modulation of toxicity, cell uptake, protein binding, and contrast agent efficiency, while at the same time allowing the stabilities of the polymersomes to be maintained. Thus, this approach holds promise for the development of a wide range of multifunctional materials for pharmaceutical applications.

Uma grande variedade de nanomateriais tem demonstrado aplicações médicas promissoras, tais como liberação de fármacos e em imagens. Nestas aplicações, a superfície química dos materiais é crítica, uma vez que exerce papel importante na determinação da toxicidade e comportamento de biodistribuição do material. Aqui, nós revisamos a funcionalização de nanomateriais, como dendrons, como método eficiente de alterar a superfície química destes compostos, introduzindo novas propriedades e funções. Descritos aqui estão nanopartículas superparamagnéticas de óxido de ferro (do inglês, SPIO), com guanidinas dendríticas para aumentar seu transporte para o interior das células, úteis em imagens de ressonância magnética. A introdução de dendrons contendo hidroxilas, aminas, guanidinas, carboidratos e quelatos de Gd(III) periféricos em vesículas poliméricas (polymersomes) também está descrita. Esses grupos dendríticos permitem a modulação de toxicidade, captura celular, ligação à proteína e eficiência como agente de contraste, enquanto que, ao mesmo tempo, permitem a manutenção da estabilidade das vesículas poliméricas. Assim, essa abordagem é promissora para o desenvolvimento de grande variedade de materiais multifuncionais para aplicações farmacêuticas.

Óleo essencial de Thymus vulgaris sobre o crescimentode Streptococcus mutans / Effect of the Thymus vulgaris essential oil on the growth of Streptococcus mutans

The traditional Mediterranean herb thyme (Thymus vulgaris) is a source of an essential oil that has been shown to possess antimicrobial activity against many microorganisms. A considerable part of the general population has dental caries and Streptococcus mutans is one of the microorganisms responsible. The aim of this study was to assess the effect of the essential oil extracted from thyme on the growth of S. mutans, the main bacterium involved in the etiology of dental caries, as well as to incorporate this oil into a toothpaste formulation for preliminary assessment. The broth dilution technique was used in threefold tests for antibacterial activity. The concentrations tested were 1%, 5% and 10% essential oil diluted in ethanol or mineral oil. The controls were triclosan at 0.25% and 0.5%, chlorhexidine digluconate at 0.06% and 0.12%, and ethanol. The 1% solution of thyme essential oil in ethanol proved to be the most efficient against Streptococcus mutans and may be considered viable as an ingredient of toothpaste, both with regard to cost and to the sensory profile of the product. Also, analyses of the characteristics of the formulation indicated that the product is stable.

Thymus vulgaris (tomilho) é uma fonte de óleo essencial que tem demonstrado atividade antimicrobiana. Uma parcela considerável da população tem apresentado problemas dentários, tais como a cárie, na qual o Streptococcus mutans é um microrganismo de fundamental importância. O objetivo deste trabalho foi avaliar o efeito do óleo essencial de tomilho sobre o crescimento do Streptococcus mutans, a principal bactéria relacionada com a etiologia da cárie dentária, bem como veicular este óleo essencial em uma formulação de creme dental para estudo preliminar. O método empregado foi diluição em caldo. As concentrações utilizadas de óleo essencial foram 1%, 5% e 10% de óleo essencial diluído em etanol ou óleo mineral. Os controles foram triclosan a 0,25% e 0,5%, bem como digluconato de clorexidina a 0,06% e 0,12%. A amostra contendo 1% de óleo essencial de tomilho diluída em etanol foi a mais eficaz, sendo efetiva contra Streptococcus mutans e, portanto considerada viável em relação ao custo e ao sensorial conferido ao produto, sendo que a formulação avaliada foi considerada estável.