The evaluation of in vitro antichagasic and anti-SARS-CoV-2 potential of inclusion complexes of ß- and methyl-ß-cyclodextrin with naphthoquinone.

The compound 3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with ß-cyclodextrin (ßCD) and methyl-ß-cyclodextrin (MßCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their in vitro anti-SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led to a change in the physicochemical characteristics compared to IVS320 alone as well as a decrease in crystallinity degree that reached 74.44% for the IVS320-MßCD one prepared by RE. The IVS320 and IVS320-MßCD/RE system exhibited anti-SARS-CoV-2 activity, showing half maximal effective concentrations (EC50) of 0.47 and 1.22 µg/mL, respectively. Molecular docking simulation suggested IVS320 ability to interact with the SARS-CoV-2 viral protein. Finally, the highest antichagasic activity, expressed as percentage of Tripanosoma cruzi growth inhibition, was observed with IVS320-ßCD/KN (70%) and IVS320-MßCD/PM (72%), while IVS320 alone exhibited only approximately 48% inhibition at the highest concentration (100 µg/mL).

Chitosan-Based Films with 2-Aminothiophene Derivative: Formulation, Characterization and Potential Antifungal Activity.

In this study, films of chitosan and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative with great pharmacological potential, were prepared as a system for a topical formulation. 6CN-chitosan films were characterized by physicochemical analyses, such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electronic microscopy (SEM). Additionally, the antifungal potential of the films was evaluated in vitro against three species of Candida (C. albicans, C. tropicalis, and C. parapsilosis). The results of the FTIR and thermal analysis showed the incorporation of 6CN in the polymer matrix. In the diffractogram, the 6CN-chitosan films exhibited diffraction halos that were characteristic of amorphous structures, while the micrographs showed that 6CN particles were dispersed in the chitosan matrix, exhibiting pores and cracks on the film surface. In addition, the results of antifungal investigation demonstrated that 6CN-chitosan films were effective against Candida species showing potential for application as a new antifungal drug.

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

In Silico Study, Physicochemical, and In Vitro Lipase Inhibitory Activity of α,ß-Amyrenone Inclusion Complexes with Cyclodextrins.

α,ß-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and ß-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.

Novel Solid Dispersions of Naphthoquinone Using Different Polymers for Improvement of Antichagasic Activity.

IVS320 (3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione) is a naphthoquinone that has low solubility in aqueous medium, a physical behavior that limits its biological activities, considering that compounds from this class have several activities. In this work, solid dispersions (SDs) prepared between IVS320 and polymers hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP) were developed using physical mixture (PM), kneading (KN), and rotary evaporation (RE) methods. Dispersions were investigated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). In addition, in vitro antiparasitic activity in Trypanosoma cruzi Y strains was evaluated. Physical-chemical characterization demonstrated the formation of SDs through the interaction of IVS320 with polymeric matrices. SDs of IVS320-polymer presented a significant potentiation of antichagasic activity, with inhibitory growth around 62% (IVS320-HPMC/RE), 55% (IVS320-PEG/RE), and 85% (IVS320-PVP/RE), while pure IVS320 showed a value of 48% for the highest concentrations evaluated (50 µg/mL).

Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities.

This review aims to provide an overview of studies that address the use, in therapeutic applications, of solid dispersions (SDs) with biological activities in vitro and/or in vivo mainly made up of polymeric matrices, as well as to evaluate the bioactive activity of their constituents. This bibliographic survey shows that the development of solid dispersions provides benefits in the physicochemical properties of bioactive compounds, which lead to an increase in their biological potential. However, despite the reports found on solid dispersions, there is still a need for biological assay-based studies, mainly in vivo, to assist in the investigation and to devise new applications. Therefore, studies based on such an approach are of great importance to enhance and extend the use of solid dispersions in the most diverse therapeutic applications.

Technological innovation strategies for the specific treatment of Chagas disease based on Benznidazole.

Caused by Trypanosoma cruzi, Chagas disease is responsible for public health problems greater in magnitude than those attributed to malaria, schistosomiasis, or leishmaniasis. A factor in the socioeconomic development of poor countries, Chagas disease can cause death due to a high parasitic burden during its acute phase due and irreversible damage in organs such as the heart, esophagus, and colon during its chronic phase, even when the number of parasites is minimal. For treating Chagas disease, benznidazole (BNZ) remains the drug of choice and, in Latin America, the only drug on the market for treating the disease. However, BNZ has exhibited insufficient activity in the chronic phase of Chagas disease, required administration in large doses, prolonged treatment, and shown a high incidence of adverse reactions (vomiting, rash, peripheral neuropathy, and spinal cord depression), toxicity, and low solubility in water. As an antidote, pharmaceutical technologies have been introduced that can improve BNZ's solubility and dissolution, as well as reduce side effects in light of its bioavailability, all of which can enhance therapy for Chagas disease. In response to that trend, by conducting a literature review, we sought to identify current pharmaceutical technologies used in tandem with BNZ to improve therapy for Chagas disease. Documented techniques include emulsion and microemulsion formation, solutions, parenteral formulas, micronization, and drug delivery systems supported by the development of nanoparticles and cyclodextrins, solid dispersions, and the use of metal-organic frameworks as innovative excipients. Such technologies increase the water solubility of BNZ by 4-25-fold on dissolution and an 85% release with efficacy in only a few minutes, as recorded during a viability experiment with nanoparticle suspensions. That experiment demonstrated the need for a lower concentration of BNZ to kill 50% of trypomastigote forms of T. cruzi, described in terms of the formation of BNZ-cyclodextrin complexes, and modulating and vectoring of the antichagasic by using metal-organic frameworks. Altogether, the promising results of research identified can enable strategies to improve solubility and efficacy of BNZ, as well as therapy for Chagas disease.

Inclusion Complexes of Copaiba (Copaifera multijuga Hayne) Oleoresin and Cyclodextrins: Physicochemical Characterization and Anti-Inflammatory Activity.

Complexation with cyclodextrins (CDs) is a technique that has been extensively used to increase the aqueous solubility of oils and improve their stability. In addition, this technique has been used to convert oils into solid materials. This work aims to develop inclusion complexes of Copaifera multijuga oleoresin (CMO), which presents anti-inflammatory activity, with ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by kneading (KND) and slurry (SL) methods. Physicochemical characterization was performed to verify the occurrence of interactions between CMO and the cyclodextrins. Carrageenan-induced hind paw edema in mice was carried out to evaluate the anti-inflammatory activity of CMO alone as well as complexed with CDs. Physicochemical characterization confirmed the formation of inclusion complex of CMO with both ß-CD and HP-ß-CD by KND and SL methods. Carrageenan-induced paw edema test showed that the anti-inflammatory activity of CMO was maintained after complexation with ß-CD and HP-ß-CD, where they were able to decrease the levels of nitrite and myeloperoxidase. In conclusion, this study showed that it is possible to produce inclusion complexes of CMO with CDs by KND and SL methods without any change in CMO's anti-inflammatory activity.

Characterization and Trypanocidal Activity of a Novel Pyranaphthoquinone.

Chagas disease is an endemic parasitic infection that occurs in 21 Latin American countries. New therapies for this disease are urgently needed, as the only two drugs available (nifurtimox and benznidazol) have high toxicity and variable efficacy in the disease's chronic phase. Recently, a new chemical entity (NCE) named Pyranaphthoquinone (IVS320) was synthesized from lawsone. We report herein, a detailed study of the physicochemical properties and in vitro trypanocidal activity of IVS320. A series of assays were performed for characterization, where thermal, diffractometric, and morphological analysis were performed. In addition, the solubility, permeability, and hygroscopicity of IVS320 were determined. The results show that its poor solubility and low permeability may be due to its high degree of crystallinity (99.19%), which might require the use of proper techniques to increase the IVS320's aqueous solubility and permeability. The trypanocidal activity study demonstrated that IVS320 is more potent than the reference drug benznidazole, with IC50/24 h of 1.49 ± 0.1 µM, which indicates that IVS320 has potential as a new drug candidate for the treatment of Chagas disease.

Análise de resíduos no processo de blistagem de comprimidos através do Controle Estatístico de Processo / Application of Statistical Process Control (SPC) to the analysis of blister waste produced in the blister packaging process

No processo de blistagem, a formação de resíduos é quase inevitável devido à própria dinâmica e o tipo de matéria prima usada no sistema. Neste trabalho, foi realizada uma análise de resíduos de blister no processo de blistagem na Divisão de Sólidos multipropósito, abordando o tipo de equipamento utilizado no processo, as características do produto formado, os principais fatores envolvidos na geração dos resíduos, e sua quantidade gerada nos lotes analisados. Foi empregada a ferramenta CEP para a análise dos resultados. Apesar de todas as variações encontradas, que avaliaram estabilidade e capacidade dos processos, todos os lotes foram aprovados frente às especificações farmacopeicas. No entanto, há provas de que o processo precisa ser melhorado e pode tornar-se mais eficiente, gerando uma economia para empresa.

In the blister packaging process, the formation of waste is almost inevitable, given the dynamics and type of raw material used in the system. In this study, an analysis of blister waste in the blistering process was carried out in the multipurpose solids Division of a pharmaceutical laboratory, with respect to the type of blister-packing machine used in the process, the characteristics of the product manufactured, the main factors involved in the generation of waste and the amount of waste in the batches analyzed. The SPC tool was used to analyze the results. Despite all the variations found in the graphical analysis of stability and process capacity, all batches complied with the pharmacopeial specifications. However, there is evidence that the process should be improved and could be made more efficient, generating savings for the company.

Pesquisa, desenvolvimento e inovação para o controle das doenças negligenciadas / Research, development and innovation for the control of neglected diseases

O fluxo contínuo de novos produtos no mercado é fruto da inovação tecnológica apresentada pela Indústria Farmacêutica. O governo Brasileiro tem investido em iniciativas promissoras de inovação através do desenvolvimento de medicamentos para os programas públicos de saúde, instituindo o Programa de Pesquisa e Desenvolvimento em Doenças Negligenciadas, o qual foca sete doenças: dengue, doenças de Chagas, leishmaniose, hanseníase, malária, esquistossomose e tuberculose. O artigo foca uma revisão sobre P&D aplicada à prevenção e controle das doenças negligenciadas no Brasil e no mundo. Com base nos dados levantados, percebeu-se que são grandes as dificuldades para o desenvolvimento de P&D em tecnologias e produtos para combater as doenças negligenciadas e que são poucos os investimentos financeiros nesse segmento quando comparados aos de pesquisas que focam outras enfermidades. Diante disso, pode-se enfatizar a importância de investimentos em pesquisas nesse setor, em saneamento básico e programas educativos que orientem a população sobre combate à proliferação dos vetores e agentes causadores.

The steady stream of new products on the market is the result of technological innovation in the pharmaceutical industry. The Brazilian government has invested in promising initiatives for innovation through the development of drugs for public health programs, setting up the Program for Research and Development on Neglected Diseases, which focuses on seven diseases: dengue fever, Chagas? disease, leishmaniasis, Hansen?s disease, malaria, schistosomiasis and tuberculosis. The article reviews the R&D applied to the prevention and control of neglected diseases in Brazil and worldwide. On the basis of survey data, we note that there are great obstacles to the development of the technology and products needed to fight neglected diseases and there are few investments in this segment in comparison with research that focuses on other diseases. In this light, we stress the importance of investment in research in this area and in sanitation and educational programs to guide the population in combating the proliferation of vectors and causative agents.