Túlio Flávio Accioly de Lima e Moura

Traditional Uses, Chemical Constituents, and Biological Activities of Bixa orellana L.: A Review

Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil and other tropical countries for several biological applications, which indicates its potential use as an active ingredient in pharmaceutical products. The aim of this work was to report the main evidence found in the literature, concerning the ethnopharmacology, the biological activity, and the phytochemistry studies related to Bixa orellana L. Therefore, this work comprises a systematic review about the use of Bixa orellana in the American continent and analysis of the data collected. This study shows the well-characterized pharmacological actions that may be considered relevant for the future development of an innovative therapeutic agent.

Application of thermal analysis to the study of antituberculosis drugs-excipient compatibility

First-line drugs (rifampicin, RIF; isoniazid, INH; ethambutol, ETA; and pyrazinamide, PZA) recommended in conventional treatment of tuberculosis were analyzed in 1:1 w/w binary mixtures with microcrystalline cellulose MC 101 (CEL) and lactose supertab® (LAC) by differential scanning calorimetry (DSC), thermogravimetry (TG), differential thermal analysis (DTA), and Fourier transformed infrared analysis (FTIR) as part of development of fixed dose combination (FDC) tablets. Evidence of interaction between drug and pharmaceutical excipients was supposed when peaks disappearance or shifting were observed on DTA and DSC curves, as well as decreasing of decomposition temperature onset and TG profiles, comparing to pure species data submitted to the same conditions. LAC was showed to interact with RIF (absence of drug fusion and recrystallization events on DSC/DTA curves); INH (thermal events of the mixtures different from those observed for drug and excipient pure in DSC/DTA curves); PZA (decrease on drug fusion peak in DSC/DTA curves), and ETA (shift on drug onset fusion and absence of pure LAC events on DSC/DTA curves). In all cases, an important decrease on the temperature of drug decomposition was verified for the mixtures (TG analysis). However, FTIR analysis showed good correlation between theoretical and experimental drug-LAC spectra except for INH–LAC mixture, evidencing high incompatibility between these two species and suggesting that those interactions with PZA and RIF were thermally induced. No evidence of incompatibilities in CEL mixtures was observed to any of the four-studied drugs.

Application of thermal analysis to the study of anti-tuberculosis drug compatibility. Part 1

Worldwide Brazil is among one of the 22 countries with high rates of tuberculosis placing this disease as a priority for the Government Health Policies in this country. Studies with the main tuberculostatic drugs rifampicin, isoniazid, pyrazinamide, and ethambutol, aiming the development of fixed-dose combination formulations (FDCs) have been performed. The aim of this study was to evaluate the thermal behavior of these drugs by DSC, TG/DTG, and DTA in order to predict possible physical and chemical interactions between tuberculostatics. DSC and DTA curves suggested incompatibility and/or interactions among drug preparations resulting from new thermal events, as well as the disappearance and shift of the melting point of the drugs. TG/DTG curves of drug mixtures presented different profiles from those observed for the individually tested drugs, supporting the evidence of drug incompatibility and indicating that mixtures are less stable when compared to the drugs alone.

Influência da temperatura de secagem e da concentração de Aerosil®200 nas características dos extratos secos por aspersão da Schinus terebinthifolius Raddi (Anacardiaceae)

Schinus terebinthifolius Raddi has been used in the Brazilian folk medicine since a long time and now as phytopharmaceutical because of its antimicrobial, cicatrizant and anti-inflammatory properties. The aim of this work was to evaluate the influence of the inlet temperature and the Aerosil concentration on the characteristics of the spray-dried extracts from Schinus terebinthifolius Raddi by spray-drying method. The extracts were prepared from a 70 °GL ethanolic extract with a Buchi B 191 Mini-spray dryer with technological adjuvant into a ratio of 20:80; 25:75 and 30:70 (w/w) Aerosil®200: dried residue, in the inlet temperature range from 120 °C to 160 °C. The residual humidity, final yield and the moisture uptake profile at 90 % Relative Humidity (RH) were used as evaluation criteria. The response surface analysis showed that increasing the temperature and the Aerosil®200 concentration, lead to lower residual humidity and moisture uptakes. The best drying parameters were the inlet temperature of 140 °C and 30 % of Aerosil®200 concentration, resulting in yields over 80 %.

Compatibility studies of trioxsalen with excipients by DSC, DTA, and FTIR

Psoralens are widely used for the treatment of psoriasis. Trioxsalen is a drug prescribed low-dose, belonging to the group of substituted psoralen. The aim of this study was to evaluate the compatibility of trioxsalen with pharmaceutical excipients used in the solid forms by analytical techniques. Binary mixtures between the trioxsalen and pharmaceutical excipients (namely, magnesium stearate, α-lactose, microcrystalline cellulose 102, pregelatinized starch, mannitol, sodium lauryl sulfate, sodium starch glycolate, and croscarmellose sodium) were examined. The trioxsalen–sodium lauryl sulfate mixture displayed some physical interaction based on the DTA and DSC results, but the FTIR study ruled out any chemical change.

Assessment of Phenolic Compounds and Anti-Inflammatory Activity of Ethyl Acetate Phase of Anacardium occidentale L. Bark

The bark of A. occidentale L. is rich in tannins. Studies have described various biological activities of the plant, including antimicrobial, antioxidant, antiulcerogenic and antiinflammatory actions. The objective of this study was to assess the activity of the ethyl acetate phase (EtOAc) of A. occidentale on acute inflammation and to identify and quantify its phenolic compounds by HPLC. The method was validated and shown to be linear, precise and accurate for catechin, epicatechin, epigallocatechin and gallic acid. Swiss albino mice (Mus musculus) were treated with saline, Carrageenan (2.5%), Indomethacin (10 mg/kg), Bradykinin (6 nmol) and Prostaglandine E2 (5 µg) at different concentrations of EtOAc - A. occidentale (12.5; 25; 50; and 100 mg/kg/weight p.o.) for the paw edema test. Challenge was performed with carrageenan (500 µg/mL i.p.) for the doses 50 and 100 mg/kg of EtOAc. Levels of cytokines IL-1, TNF-α, IL-6 and IL-10 were also measured. All EtOAc - A. occidentale concentrations reduced the edema. At 50 and 100 mg/kg, an anti-inflammatory response of the EtOAc was observed. Carrageenan stimulus produced a neutrophil count of 28.6% while 50 and 100 mg/kg of the phase reduced this to 14.5% and 9.1%, respectively. The EtOAc extract reduced levels of IL-1 and TNF-α. These results suggest that the EtOAc plays a modulatory role in the inflammatory response. The chromatographic method can be used for the analysis of the phenolic compounds of the EtOAc phase.

Characterization of palygorskite clay from Piauí, Brazil and its potential use as excipient for solid dosage forms containing anti-tuberculosis drugs

Clays play an important role in health products as it has been used as excipients for solid dosage forms and as active ingredients. Usually, excipients are pharmacologically inert, but they can interact with drugs in the solid dosage form and affect their bioavailability. Thus, the aim of this work was to determinate the physicochemical properties of palygorskite clay from Piauí, Brazil, and to investigate the potential use of this mineral as excipient for solid dosage forms containing rifampicin and isoniazid, which are drugs currently used to treat tuberculosis. Palygorskite was analyzed by X-ray fluorescence, X-ray diffraction, transmission electron microscopy, and particle size analyzer. According to the results, the main component found was SiO2, and its mineral composition contains palygorskite, dolomite, and quartz. The particles appear as fibers with bundle-like aspect that cluster together to form aggregates. The results from thermal analysis indicate that there is no interaction between both rifampicin and isoniazid with palygorskite. Moreover, the presence of palygorskite did not interfere on the dissolution of these drugs, which suggests that this material can be potentially used as an excipient for these drugs.

Use of chemometrics to compare NIR and HPLC for the simultaneous determination of drug levels in fixed-dose combination tablets employed in tuberculosis treatment

Graphical abstract Figure. No caption available. HighlightsSimple, quick, inexpensive and non‐destructive technique, it does not employ organic solvents, thus protecting the environment.The models developed by NIR in association with multivariate analysis provided good prediction of the APIs for the external samples.The tablets led to results that were not statistically similar, despite having prediction errors considered acceptable in the literature.PAT technology: models using the same amount of excipients contained in the tablets need to be developed. ABSTRACT The World Health Organization recommends that TB treatment be administered using combination therapy. The methodologies for quantifying simultaneously associated drugs are highly complex, being costly, extremely time consuming and producing chemical residues harmful to the environment. The need to seek alternative techniques that minimize these drawbacks is widely discussed in the pharmaceutical industry. Therefore, the objective of this study was to develop and validate a multivariate calibration model in association with the near infrared spectroscopy technique (NIR) for the simultaneous determination of rifampicin, isoniazid, pyrazinamide and ethambutol. These models allow the quality control of these medicines to be optimized using simple, fast, low‐cost techniques that produce no chemical waste. In the NIR – PLS method, spectra readings were acquired in the 10,000–4000 cm−1 range using an infrared spectrophotometer (IRPrestige – 21 – Shimadzu) with a resolution of 4 cm−1, 20 sweeps, under controlled temperature and humidity. For construction of the model, the central composite experimental design was employed on the program Statistica 13 (StatSoft Inc.). All spectra were treated by computational tools for multivariate analysis using partial least squares regression (PLS) on the software program Pirouette 3.11 (Infometrix, Inc.). Variable selections were performed by the QSAR modeling program. The models developed by NIR in association with multivariate analysis provided good prediction of the APIs for the external samples and were therefore validated. For the tablets, however, the slightly different quantitative compositions of excipients compared to the mixtures prepared for building the models led to results that were not statistically similar, despite having prediction errors considered acceptable in the literature.

Gastric-resistant isoniazid pellets reduced degradation of rifampicin in acidic medium

Isoniazid and rifampicin are considered the first-line medication for preventing and treating tuberculosis. Rifampicin is degraded in the stomach acidic environment, especially when combined with isoniazid, factor contributing to treatment failure. In this study, gastric-resistant isoniazid pellets were obtained to physical contact of this drug with rifampicin and to bypass the stomach´s acidic environment. The pellets were fabricated using the extrusion-spheronization technique. The coating process was conducted in a fluid spray coater using Acrycoat L 100(r) solution as the coating agent. The pellets obtained were submitted to a dissolution test in HCl 0.1 N and phosphate buffer media. The results indicated that optimum gastric-resistance was only attained with the highest amount of coating material, with isoniazid almost fully released in phosphate buffer. The amount of rifampicin released from its mixture with non-coated isoniazid pellets in HCl 0.1 N was less than that released from its mixture with the enteric-coated pellets. Acrycoat L 100(r) was shown to be an effective enteric/gastric-resistant coating since the stability of rifampicin appeared to be enhanced when physical contact of this drug with isoniazid was prevented at low pH.