Development and evaluation of the in vitro schistosomicidal activity of solid dispersions based on 2-(-5-bromo-1-H-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide.

Among all the neglected diseases, schistosomiasis is considered the second most important parasitic infection after malaria. Praziquantel is the most widely used drug for this disease, but its exclusive use may result in the development of drug-resistant schistosomiasis. To increase the control of the disease, new drugs have been developed as alternative treatments, among them 2-(-5-bromo-1-h-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide (LQIT/LT-50), which showed promising schistosomicidal activity in nonclinical studies. However, LQIT/LT-50 presents low solubility in water, resulting in reduced bioavailability. To overcome this solubility problem, the present study aimed to develop LQIT/LT-50 solid dispersions for the treatment of schistosomiasis. Solid dispersions were prepared through the solvent method using Soluplus©, polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP K-30) as hydrophilic carriers. The formulations with the best results in the compatibility tests, aqueous solubility and preliminary stability studies have undergone solubility tests and physicochemical characterizations by Fourier-transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), exploratory differential calorimetry (DSC), thermogravimetry (TG) and Raman spectroscopy. Finally, the schistosomicidal activity was evaluated in vitro. The phycochemical analyzes showed that when using PVP K-30, there was an interaction between the PVP K-30 and LQIT/LT-50, proving the successful development of the solid dispersion. Furthermore, an increase in the solubility of the new system was observed (LQIT/LT-50:PVP K-30) in addition to the improvement in the in vitro shistosomidal activity at 1:4 (w/w) molar ratio (i.e., 20% drug loading) when compared to LQIT/LT-50 alone. The development of the LQIT/LT-50:PVP K-30 1:4 solid dispersion is encouraging for the future development of new pharmaceutical solid formulations, aiming the schistosomicidal treatment.

Antitussive, Expectorant and Antipyretic Effect of the Ethanolic Extract of the Leaves of Momordica charantia L.

The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.

Benznidazole in vitro dissolution release from a pH-sensitive drug delivery system using Zif-8 as a carrier.

Chagas disease is a neglected tropical disease caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). Endemic in underdeveloped and developed countries, due to the migratory movement, it is considered a serious public health problem. Endemic in underdeveloped countries and due to the migratory movement, in developed countries as well, it is considered a serious public health problem. One of the reasons for this is a weak therapeutic arsenal, represented only by the drug benznidazole (BNZ) which, although it promotes significant cure rates in the acute phase of the disease, presents serious problems of toxicity and bioavailability, mainly due to its low aqueous solubility. Several studies have presented several drug delivery systems (DDS) based on BNZ aiming at enhancing its solubility in aqueous medium and, with this, promoting an increase in the dissolution rate and, consequently, in its bioavailability. However, the present work is a pioneer in using a zeolitic imidazolate framework as a carrier agent for a DDS in order to promote a pH-sensitive modulation of the drug. Thus, this work aimed to develop a novel DDS based on BNZ and the ZIF-8 to use it in development of prolonged-release dosage forms to alternative treatment of Chagas disease. The BNZ@ZIF-8 system was obtained through an ex situ method selected due to its higher incorporation efficiency (38%). Different characterization techniques corroborated the obtainment and drug release data were analyzed by in vitro dissolution assay under sink and non-sink conditions and setting the kinetic results through both model dependent and independent methods. Under sink conditions, at pH 4.5, BNZ and BNZ@ZIF-8 showed similar release profile, but the DDS was effective in promoting a prolonged release. At pH 7.6, after 7 h, BNZ showed a lower release than BNZ@ZIF-8. On the other hand, in non-sink conditions at pH 4.5 the BNZ presented 80% of drug release in 3 h, while the DDS in 6 h. At pH 7.6, BNZ presented a release of 80% in 2 h, while the DDS reaches it in only at 12 h. Therefore, at pH 4.5 the DDS BNZ@ZIF-8 showed a faster release with a burst effect, while at pH 7.6 it showed a prolonged and controlled release. Finally, it is evident that a promising DDS pH-sensitive was obtained as a novel carrier that might be able to prolongs BNZ release in dosage forms intended for the alternative treatment of Chagas disease.

Product indiscriminate use of vitamin risks: A review.

Most of the population does not seek professional advice before taking vitamin products and their indiscriminate use can lead to serious health risks. This study aims to demonstrate, through bibliographic survey, the risks of indiscriminate use of vitamin products related to hypervitaminosis and major drug interactions which the multivitamins are involved. A bibliographic survey was conducted in the databases LILACS, SciELO, PubMed, Medline, Micromedex, Drugs.com and textbooks on the subject. Vitamins are commonly described as harmless products by the majority of the population, but these trace elements can interact with other substances, causing mild disconforts or treatment failure for the patient, severe consequences to the body and can lead to death. To avoid the indiscriminate use of vitamin products, it is necessary that health professionals know and use specific laboratory tests for the determination of vitamins in the body, preventing these products from being unnecesarily prescribed. Also, the knowledge about what the possible effects of the indiscriminate use of vitamin supplements can lead to the rational use of these products.

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis.

Considered prevalent in many countries on five continents, especially in low-income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.

Development and Evaluation of Antimicrobial and Modulatory Activity of Inclusion Complex of Euterpe oleracea Mart Oil and ß-Cyclodextrin or HP-ß-Cyclodextrin.

The development of inclusion complexes is used to encapsulate nonpolar compounds and improve their physicochemical characteristics. This study aims to develop complexes made up of Euterpe oleracea Mart oil (EOO) and ß-cyclodextrin (ß-CD) or hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by either kneading (KND) or slurry (SL). Complexes were analyzed by molecular modeling, Fourier-transform infrared spectroscopy, scanning electron microscopy, powder X-ray diffraction, thermogravimetry analysis and differential scanning calorimetry. The antibacterial activity was expressed as Minimum Inhibitory Concentration (MIC), and the antibiotic resistance modulatory activity as subinhibitory concentration (MIC/8) against Escherichia coli, Streptomyces aureus, Pseudomonas aeruginosa and Enterococcus faecalis. Inclusion complexes with ß-CD and HP-ß-CD were confirmed, and efficiency was proven by an interaction energy between oleic acid and ß-CD of -41.28 ± 0.57 kJ/mol. MIC values revealed higher antibacterial activity of complexes compared to the isolated oil. The modulatory response of EOO and EOO-ß-CD prepared by KND as well as of EOO-ß-CD and EOO-HP-ß-CD prepared by SL showed a synergistic effect with ampicillin against E. coli, whereas it was not significant with the other drugs tested, maintaining the biological response of antibiotics. The antimicrobial response exhibited by the complexes is of great significance because it subsidizes studies for the development of new pharmaceutical forms.

Development and Evaluation of Photoprotective O/W Emulsions Containing Hydroalcoholic Extract of Neoglaziovia variegata (Bromeliaceae).

Neoglaziovia variegata is a Bromeliaceae plant species widely found in Brazil with several pharmacological properties, including photoprotective activity. Although herbal-based active ingredients have been applied in cosmetic products, especially for skin treatment, its application in sunscreen formulations remains unexplored. The aim of this work is to evaluate the photoprotective effect of cosmetic formulations containing hydroalcoholic extract of N. variegata (Nv-HA). Initially, the phenolic and flavonoid total content of Nv-HA were determined. The photoprotective activity of Nv-HA was subsequently assessed using a spectrophotometric method. Nv-HA was incorporated in O/W emulsions in the presence or absence of synthetic filters and their photoprotective efficacy was evaluated by spectrophotometric SPF determination. Finally, the stability study of the formulations was performed through the freezing/defrosting method. Nv-HA showed significant phenolic and flavonoids content (61.66 ± 5.14 mg GAE/g and 90.27 ± 5.03 mg CE/g, resp.). Nv-HA showed SPF values of 5.43 ± 0.07 and 11.73 ± 0.04 for the concentrations of 0.5 and 1.0% (v/v), respectively. It was verified that Nv-HA potentiated the photoprotective effect of formulations containing only synthetic filters. Furthermore, the formulations have remained stable at the end of the preliminary stability study. According to the results, it was concluded that Nv-HA can be used as a chemical filter in cosmetic formulations.

Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study.

Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

Development and Evaluation of Stability of a Gel Formulation Containing the Monoterpene Borneol.

Borneol is a bicyclic monoterpenoid alcohol commonly used in traditional Chinese and Indian medicine. It is extracted from the essential oil of various medicinal plants. It has antibacterial, analgesic, and anti-inflammatory action proven in studies that used oral and intraperitoneal applications of this monoterpene in mice. The current study was designed to develop a topical gel formulation containing the monoterpene borneol using carbopol as gel base and to evaluate its stability. The prepared formulation was subjected to physical characterization and physical-chemistry assessment. The gel was prepared from carbopol and 5% of borneol. The prepared gel was subjected to pharmacotechnical tests such as its pH, viscosity, conductivity, spreadability, centrifugation, and accelerated stability with freezing-thaw cycle. The borneol was successfully incorporated into the carbopol formulation. Borneol gel (BG5) showed good stability after eight months of its development and after 12 days in the freeze-thaw cycle, not showing statistical difference in pH value, conductivity, and viscosity before and after test. Furthermore, the formulation showed a good spreadability. Therefore, it was concluded that the formulation could be very promising alternative for the topical or transdermal treatment of skin diseases.

A study of photostability and compatibility of the anti-chagas drug Benznidazole with pharmaceutics excipients.

UNLABELLED: Abstract Context: Benznidazole (BNZ) is an antiparasitic with trypanocidal properties for the etiological treatment of Chagas disease since 1973. Monitoring the stability of this drug is one of the most effective methods of assessment, forecasting and prevention of problems related to quality product. OBJECTIVE: To investigate the direct and indirect photodegradation of BNZ and to evaluate the interference of the excipients used in the forms dosage solid as well as to shed light on the chemical structure of the degradation products obtained. MATERIALS AND METHODS: To perform this work we adopted the "ICH Harmonised Tripartite Guideline: Photostability Testing of New Drug Substances and Products Q1B" (Guideline Q1B). We used benzonidazole (BNZ) (N-benzil-2-(2-nitroimidazol-1-il) acetamide) (LAFEPE®, Recife, Brazil) and various excipients; beyond high-performance liquid chromatography (HPLC), differential scanning calorimetry (DSC), infrared spectroscopy (IR) and mass spectrometry/mass spectrometry (MS/MS). The indirect photodegradation of BNZ was carried out using physical mixtures with 13 pharmaceutical excipients commonly used in the preparation of solid dosage forms. RESULTS: HPLC and MS/MS techniques were selected for the identification of two photoproducts (PPs) and photoreactions found in direct and indirect tests with the microcrystalline cellulose, considered a critical excipient. DISCUSSION: Despite variations in the infrared spectrometry, differential scanning calorimetry and differential thermogravimetry curves, these techniques are not conclusive since the study of photodegradation of the drug caused decay of 30%, according to the ICH. CONCLUSIONS: The results show that BNZ only undergoes direct photodegradation, since no new PPs were found for a combination of the drug and excipients.

Herbal Technological Prospects of Morus nigra L.: A Systematic Patent Analysis Review.

BACKGROUND: Morus nigra L. is a plant with significant potential for drug development due to the presence of numerous bioactive compounds in its various parts. OBJECTIVES: This article aims to compile the technological perspectives of Morus nigra L. towards drug development and therapeutic indications based on registered patents in databases. METHODS: The study analyzed patents published within the last five years, focusing on products derived from different parts of the Morus nigra L. plant. Patent databases such as the European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), the World Intellectual Property Organization (WIPO), and the National Institute of Industrial Property Databases (INPI) were examined. RESULTS: A total of 45 patents were categorized by country of origin, type of applicant, extraction method, and therapeutic indications. China had the highest number of patent filings (43.48%), and private companies were the primary technology patent holders (38.64%). Noteworthy extraction methods included ultrasound-assisted extraction, decoction, infusion, and maceration. The most utilized plant parts were leaves (44.44%), followed by fruits (35.56%), root bark (15.56%), and stems (4.44%). The main therapeutic indications identified were the treatment of hyperglycemia and dyslipidemia (43.33%), along with digestive problems, cosmetics, nutrition, and cleaning applications. CONCLUSION: The study of patents covers discoveries and advancements often absent in scientific articles, making a review focused on this advanced information crucial for expanding existing scientific knowledge. Even if some therapies have been explored previously, patents can reveal innovative approaches and fresh perspectives that contribute to sustained scientific progress.

pH-responsive phthalate cashew gum nanoparticles for improving drugs delivery and anti-Trypanosoma cruzi efficacy.

Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.

Drug associations as alternative and complementary therapy for neglected tropical diseases.

The present paper aims to establish different treatments for neglected tropical disease by a survey on drug conjugations and possible fixed-dose combinations (FDC) used to obtain alternative, safer and more effective treatments. The source databases used were Science Direct and PubMed/Medline, in the intervals between 2015 and 2021 with the drugs key-words or diseases, like "schistosomiasis", "praziquantel", "malaria", "artesunate", "Chagas' disease", "benznidazole", "filariasis", diethylcarbamazine", "ivermectin", " albendazole". 118 works were the object of intense analysis, other articles and documents were used to increase the quality of the studies, such as consensuses for harmonizing therapeutics and historical articles. As a result, an effective NTD control can be achieved when different public health approaches are combined with interventions guided by the epidemiology of each location and the availability of appropriate measures to detect, prevent and control disease. It was also possible to verify that the FDCs promote a simplification of the therapeutic regimen, which promotes better patient compliance and enables a reduction in the development of parasitic resistance, requiring further studies aimed at resistant strains, since the combined APIs usually act by different mechanisms or at different target sites. In addition to eliminating the process of developing a new drug based on the identification and validation of active compounds, which is a complex, long process and requires a strong long-term investment, other advantages that FDCs have are related to productive gain and gain from the industrial plant, which can favor and encourage the R&D of new FDCs not only for NTDs but also for other diseases that require the use of more than one drug.

Cutaneous leishmaniasis: new oral therapeutic approaches under development.

The World Health Organization (WHO) classifies leishmaniasis as a disease for which the development of new treatments is a priority. Available drugs are not fully effective in all cases; they have parenteral administration and exhibit serious and common adverse effects. The only oral drug available (miltefosine) has shown resistance, is expensive, and is not available in many endemic countries. Thus, the development of an oral medicine may solve many of these issues. Based on that, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs for the treatment of cutaneous leishmaniasis. A literature search for keywords "leishmania and oral" was performed in PubMed and ScienceDirect, considering articles published in the last 5 years. The articles were selected based on the objective of the review. The main problem in the current treatment of leishmaniasis is the administration of injectables, since it requires patients to travel to health centers, hospitalization, and professional administration, conditions that are not adapted to the socioeconomic reality of patients. Therefore, many research studies have evaluated oral alternatives for the treatment of cutaneous leishmaniasis. The main tested approaches were obtaining new molecules, repositioning drugs, and new formulations of old drugs. The prospects are encouraging but still require more in vivo bioavailability and clinical trials.

A Review of Analytical Methods for Calcium Salts and Cholecalciferol in Dietary Supplements.

Dietary supplements composed by the combination of a calcium salt with cholecalciferol (vitamin D3) are widely used for improving bone health in conditions caused by the deficiency of these compounds in the body. Historically, these supplements have been linked to quality and safety issues. In the case of calcium salts, the presence of potentially toxic contaminants such as lead (Pb) has already been alerted by health authorities from different countries. Meanwhile, cholecalciferol is very unstable under inadequate manufacturing and storage conditions. The content of both compounds in commercial dietary supplements is often found to be in disagreement with the label claims, which can lead to a deficient or excessive nutrient intake by consumers. In this scenario, analyzing these compounds is still a difficult and time-consuming task, which usually requires specific pretreatment procedures and multiple analytical methods due to the inorganic nature of calcium and the organic nature of cholecalciferol. Therefore, this article reviews the analytical methods, described in official compendia and scientific literature, for the determination of calcium salts and cholecalciferol in dietary supplement formulations. We also approached the sample preparation procedures highly required due to the matrix complexity of these materials.

Metal organic frameworks (MOFs) with therapeutic and biomedical applications: a patent review.

Introduction: Metal organic frameworks (MOFs) are a recent group of nano porous materials with exceptional physical properties, such as large surface areas, high pore volumes, low densities and well-defined pores. This type of material has been used frequently for biomedical and therapeutic applications, such as drug delivery systems and theranostic materials.Areas covered: In this review, the authors searched for patents filed in the last 10 years, found in different databases, related to the therapeutic or biomedical application of MOFs for use in different health fields. The possibility of these new materials becoming new therapeutic possibilities available to the population was emphasized.Expert opinion: The advances in research with MOFs have grown in the last 10 years and with that many possibilities for their applications have emerged in several areas, especially biomedical. The possibility of using these materials in drug delivery systems is the most common form of possibility of use in the health area, mainly due to easy obtaining and high reproducibility, which are seen very positively by the drug development technology sector.

Microwave-initiated rapid synthesis of phthalated cashew gum for drug delivery systems.

Chemical modification of polysaccharides is an important approach for their transformation into customized matrices that suit different applications. Microwave irradiation (MW) has been used to catalyze chemical reactions. This study developed a method of MW-initiated synthesis for the production of phthalated cashew gum (Phat-CG). The structural characteristics and physicochemical properties of the modified biopolymers were investigated by FTIR, GPC, 1H NMR, relaxometry, elemental analysis, thermal analysis, XRD, degree of substitution, and solubility. Phat-CG was used as a matrix for drug delivery systems using benznidazole (BNZ) as a model drug. BNZ is used in the pharmacotherapy of Chagas disease. The nanoparticles were characterized by size, PDI, zeta potential, AFM, and in vitro release. The nanoparticles had a size of 288.8 nm, PDI of 0.27, and zeta potential of -31.8 mV. The results showed that Phat-CG has interesting and promising properties as a new alternative for improving the treatment of Chagas disease.

Beta-lapachone: Natural occurrence, physicochemical properties, biological activities, toxicity and synthesis.

ß-Lapachone is an ortho-naphthoquinone originally isolated from the heartwood of Handroanthus impetiginosus and can be obtained through synthesis from lapachol, naphthoquinones, and other aromatic compounds. ß-Lapachone is well known to inhibit topoisomerase I and to induce NAD(P)H: quinone oxidoreductase 1. Currently, phase II clinical trials are being conducted for the treatment of pancreatic cancer. In view of ever-increasing scientific interest in this naphthoquinone, herein, the authors present a review of the synthesis, physicochemical properties, biological activities, and toxicity of ß-lapachone. This natural compound has shown activity against several types of malignant tumors, such as lung and pancreatic cancers and melanoma. Furthermore, this ortho-naphthoquinone has antifungal and antibacterial activities, underscoring its action against resistant microorganisms and providing anti-inflammatory, antiobesity, antioxidant, neuroprotective, nephroprotective, and wound-healing properties. ß-Lapachone presents low toxicity, with no signs of toxicity against alveolar macrophages, dermal fibroblast cells, hepatocytes, or kidney cells.

Obtainment of the spray-dried extracts of Peperomia pellucida L. (H.B.K.) using different atomization temperatures: physicochemical characterization and technological development for pharmaceutical applications.

Spray-dried extracts are prepared as powders or granules after solvent removal, which can be obtained in the presence or absence of pharmaceutical adjuvants. This work aimed to optimize the process of obtaining dried extracts of Peperomia pellucida L. (HBK) by spray drying. The characterization of the extract was performed by thermal analysis, specific surface area, particle size and high performance liquid chromatography (HPLC); then, capsules were developed for antimicrobial treatment, evaluating four bench lots by the determination of the angle of repose and time of flow, scanning electron microscopy, porosity and physicochemical quality control. There were no significant differences between the extracts obtained by spray drying at atomization temperatures of 140 °C, 160 °C and 180 °C, which was confirmed by thermal analysis. Specific surface area varied inversely with the mean particle size. Regarding the marker content by HPLC, no significant differences were found between the samples, although the flavonoid fraction was more stable at 160 °C. Bench lots (I to IV) were developed using the diluents Flowlac®, Starch® 1500, microcrystalline cellulose 250 and Cellactose® 80. Based on the results, the bench lot I, containing Flowlac®, was selected. The results of physicochemical quality control demonstrated that the selected formulation meets the pre-established parameters, and proving to be economically viable.

A preformulation study of a new medicine for Chagas disease treatment: physicochemical characterization, thermal stability, and compatibility of benznidazole.

This work aimed the studies of physicochemical characterization, thermal stability, and compatibility of benznidazole (BNZ) drug by spectroscopy (NMR, IR), thermoanalytical (differential thermal analysis, differential scanning calorimetry, and thermogravimetry), and chromatographic (HPLC) techniques, beyond the analytical tools of Van't Hoff equation and Ozawa model. The compatibility study was conducted by binary mixtures (1:1, w/w) of the drug with microcrystalline cellulose 102 and 250, anhydrous lactose, and sodium starch glycolate. The physicochemical characterization confirmed data reported in scientific literature, guaranteeing authenticity of the analyzed raw material. The drug melts at 191.68°C (∆H, 119.71 J g(-1)), characteristic of a non-polymorphic raw material, and a main stage decomposition at 233.76-319.35°C (∆m, 43.32%) occurred, ending the study with almost all mass volatilized. The quantification of drug purity demonstrated a correlation of 99.63% between the data obtained by chromatographic (99.20%) and thermoanalytical technique (99.56%). The Arrhenius equation and Ozawa model showed a zero-order kinetic behavior for the drug decomposition, and a calculated provisional validity time was 2.37 years at 25°C. The compatibility study evidenced two possible chemical incompatibilities between BNZ and the tested excipients, both associated by the authors to the reaction of the BNZ's amine and a polymer carbohydrate's carbonile, being maillard reactions. The BNZ reaction with anhydrous lactose is more pronounced than with the sodium starch glycolate because the lactose has more free hydroxyl groups to undergo reduction by the drug. In this sense, this work guides the development of a new solid pharmaceutical product for Chagas disease treatment, with defined quality control parameters and physicochemical stability.