Submission of Rifaximin to Different Techniques: Characterization, Solubility Study, and Microbiological Evaluation.

Rifaximin, an oral antimicrobial drug, is marketed as 200-mg tablets. The daily dose ranges from 600 mg (1 tablet 3 times a day) to 800 mg (2 tablets twice a day). It is used for a wide range of ages, from adults to children, since it is indicated for the treatment of hepatic encephalopathy, travelers' diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis, and acute diarrhea. The success of pharmacotherapy will depend on correct fulfillment of drug administration; however, it becomes difficult when the tablets are large and the doses are frequent. Rifaximin belongs to class IV according to the Biopharmaceutic Classification System (BCS), meaning that it is both poorly soluble and poorly permeable. Thus, in this study, solubility of rifaximin was improved by its complexation to ß-cyclodextrin by (i) phase solubility diagram, (ii) malaxation, and (iii) decreasing particle size by wet milling. Improved solubility provides lower doses and facilitates compliance with pharmacotherapy. The products formed were analyzed by spectrophotometry in the infrared region (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Also, their solubility and microbiological activity were determined. The products obtained in all techniques were more soluble than the free drug; they presented higher thermal stability and antimicrobial potency was approximately 100% with all the formulations. It is important to highlight that the treatment failure not only affects the quality of life of the patients, but also contributes significantly to the economic burden of the health system. Therefore, these findings are extremely interesting, both from a technological and financial point of view.

Evolution of green chemistry and its multidimensional impacts: A review.

The growing process of industrialization was a milestone for world economic evolution. Since the 1940s, social movements have revolutionized green chemistry and provided shifts in industrial positions and sustainable processes with advances in environmental impact and awareness of companies and population. Paul Anastas and John Warner, in the 1990s, postulated the 12 principles of Green Chemistry, which are based on the minimization or non-use of toxic solvents in chemical processes and analyzes, as well as, the non-generation of residues from these processes. One of the most active areas of Research and Development in Green Chemistry is the development of analytical methodologies, giving rise to the so-called Green Analytical Chemistry. The impacts of green chemistry on pharmaceutical analyzes, environmental, population, analyst and company are described in this review and they are multidimensional. Every choice and analytical attitude has consequences both in the final product and in everything that surrounds it. The future of green chemistry as well as our future and the environment is also contemplated in this work.

Development of differentiated pharmaceutical packaging for greater autonomy and quality of life for physically and visually impaired patients.

20-45% of the world population present special needs, permanent or provisional. This index is higher than that presented by the WHO, which determines that 10% of a country's population has some kind of disabled, in times of peace. This work proposes, focused on Assistive Technology, to seek solutions to daily problems encountered during the distribution of toothpaste for the toothbrushing of persons with visual impairment or with reduced mobility, through the development of a device that assists in the autonomy and independence of the individual, allowing their well-being and social inclusion. For this, an innovative packaging for toothpaste with important characteristics for the support was proposed, such as the presence of a pump valve and an adapter that guides the user to locate the exit of a predefined quantity of the toothpaste, without the need to handle the bristles of the brush, avoiding contaminations. The developed packaging material allows the user independence in day-to-day activities, which strengthens their self-esteem and quality of life, leading, consequently, to family well-being.

Release and permeation profiles of spray-dried chitosan microparticles containing caffeic acid.

Caffeic acid (CA), a phenolic compound found in plants with antioxidant and antimicrobial activity, induces collagen production and prevents premature aging of the skin. The objective of this study was to develop two types of chitosan microparticles (MP) containing CA and to relate the morphology with the release and permeation profiles. One type of MP was prepared from a hydroalcoholic solution (MPI) and the other from an aqueous solution (MPII). Their morphology and size was evaluated by high-resolution scanning electron microscopy. The release profile of CA was evaluated using the cellulose membrane from the two MPs in Franz diffusion cells and the permeation profile was evaluated using human abdominal skin samples; the epidermal membranes were prepared by the heat-separation technique. MPII was spherical with a smooth surface, suitable for the controlled release of substances, whereas MPI was porous with non-internalized residual material. This result was consistent with their release and permeation profiles because MPII exhibited a slower and more controlled release than MPI. Thus, the method of preparation of MP and their composition influence the release profile of CA. Therefore, the production conditions must be closely controlled.

Synthetic detergents: 100 years of history.

In the year 2016 the synthetic detergents complete 100 years and in this story they evolved as cleaners. They are already part of the routine of thousands of people worldwide. For a higher power of cleaning of the detergent, today, are added phosphates, the main responsible for environmental problems. After 100 years of synthetic detergents, the effect of the combination of various cleaners on the environment is a gap. Legislation and guidelines about the other components of the formula of cleaners still missing. Even the term biodegradable can be best placed on the diversity of products currently entitled biodegradable. A lot attitudes can still be taken to continuously improve the relationship between the parties involved, animals, plants, waters and men, so that in another 100 years continues to exist this interaction with the environment without destroying it. The marketing used by synthetic detergent companies evolved a lot over the years and showed maturity to deal with changes in theories and strategies for promotion and even with the constant social reform that its consumer lived, accompanying them intelligently to be able to capture their changing needs and desires, and so assemble the best way to connect to them. This paper focuses on the subject synthetic detergents as well as (i) types and applications, (ii) threats, (iii) sustainability, (iv) legislation, (v) packaging and (vi) marketing strategies.

Daptomycin: Physicochemical, Analytical, and Pharmacological Properties.

Daptomycin is the first approved member of a new class of antimicrobials, the cyclic lipopeptides, and presents selective action against gram-positive bacteria, including methicillin- and vancomycin-resistant strains. Considering that resistance to daptomycin is rare, the drug has become very important for current clinical practice. This review covers daptomycin's physicochemical characteristics, antibacterial spectrum, mechanism of action, pharmacokinetics, clinical applications, side effects, drug interactions, and the analytical methods used to measure daptomycin in pharmaceutical products and biologic samples. Special attention has been given to therapeutic drug monitoring reports, as studies have shown its highly variable pharmacokinetics in specific circumstances, such as in patients suffering from critical illness, morbid obesity, severe sepsis, and kidney injury. For the same reason, methods described for therapeutic drug monitoring of daptomycin in the special patient population have been reviewed. In addition, the review presents a discussion of environmentally friendly analytical methods for daptomycin, which are necessary to reduce the impact of our activities on the environment. However, it was observed that there is a gap in the literature in this regard and further research involving the development of "green" methodologies for the analysis of daptomycin is necessary. The review will be useful to the clinical community in assisting with the responsible use of daptomycin, which is critical to prevent the emergence of resistant strains.

Development, Optimization, and Validation of a Green and Stability-Indicating HPLC Method for Determination of Daptomycin in Lyophilized Powder.

Daptomycin is an antimicrobial that plays an important role in clinical practice today because it is considered a promising drug to combat resistant strains, such as methicilin and vancomycin-resistant Gram-positive bacteria. Considering the analysis of daptomycin in a pharmaceutical dosage form, the only method found in literature uses potentially toxic organic solvents. Therefore, the objective of this work was to develop a green and stability-indicating HPLC method for determination of daptomycin in lyophilized powder. The mobile phase was ethanol-water (55+45, v/v) at pH 4.5 pumped at a flow rate of 0.6 mL/min. A C18 column was used, and UV detection was performed at 221 nm. Stress degradation studies were conducted in order to demonstrate the specificity and stability-indicating capability of the method. The method was validated according to International Conference on Harmonization guidelines, proving to be linear (r=0.9996), precise, accurate, robust (demonstrated by the Plackett-Burman model), and specific within the range 20-70 µg/mL. The retention time of daptomycin was 5.8 min. It can be concluded that the validated method can be a fast, safe, and environmentally friendly alternative for the analysis of daptomycin.

Antioxidant Activity and Validation of Quantification Method for Lycopene Extracted from Tomato.

Lycopene is a carotenoid found in tomatoes with potent antioxidant activity. The aim of the study was to obtain an extract containing lycopene from four types of tomatoes, validate a quantification method for the extracts by HPLC, and assess its antioxidant activity. Results revealed that the tomatoes analyzed contained lycopene and antioxidant activity. Salad tomato presented the highest concentration of this carotenoid and antioxidant activity. The quantification method exhibited linearity with a correlation coefficient of 0.9992. Tests for the assessment of precision, accuracy, and robustness achieved coefficients with variation of less than 5%. The LOD and LOQ were 0.0012 and 0.0039 µg/mL, respectively. Salad tomato can be used as a source of lycopene for the development of topical formulations, and based on performed tests, the chosen method for the identification and quantification of lycopene was considered to be linear, precise, exact, selective, and robust.

Influence of ß-cyclodextrin on the Properties of Norfloxacin Form A.

Cyclodextrins are able to form host-guest complexes with hydrophobic molecules to result in the formation of inclusion complexes. The complex formation between norfloxacin form A and ß-cyclodextrin was studied by exploring its structure affinity relationship in an aqueous solution and in the solid state. Kneading, freeze-drying, and physical mixture methods were employed to prepare solid complexes of norfloxacin and ß-cyclodextrin. The solubility of norfloxacin significantly increased upon complexation with ß-cyclodextrin as demonstrated by a solubility isotherm of the AL type along with the results of an intrinsic dissolution study. The complexes were also characterized in the solid stated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffractometry, scanning electron microscopy (SEM), and solid-state nuclear magnetic resonance (ssNMR) spectrometry. The thermal analysis showed that the thermal stability of the drug is enhanced in the presence of ß-cyclodextrin. Finally, the microbiological studies showed that the complexes have better potency when compared with pure drug.

Pharmacological, toxicological and phytochemical analysis of Spondias dulcis parkinson.

Spondias dulcis Parkinson have been used in traditional medicine in Asia, Oceania, and South America, for different diseases conditions and as a functional food. The scientific literature described as different potential pharmacology such as antioxidant, anti-inflammatory, antimicrobial, thrombolytic and enzymatic inhibitor. This study aimed to: (1) establish the pharmacological activity in intestinal motility in vivo and antioxidant activity in vitro; (2) perform the acute toxicology test in mouse; (3) characterize the phytochemical profile based on counter-current chromatography (CCC) and NMR analysis. The results revealed a laxative effect of S. dulcis extract and a high antioxidant activity (IC50 = 5.10 for DPPH assay and 14.14 for hydrogen peroxide scavenging test). No side effects were observed in the oral acute toxicity test for a dose up to 2000 mg/kg. The chemical profile was identified by CCC and NMR, and the comparison of the data obtained with previous literature revealed the presence of the flavonoid rutin (Quercetin-3-O-rutinoside) in the extract.

A Clean, Sustainable and Stability-Indicating Method for the Quantification of Ceftriaxone Sodium in Pharmaceutical Product by HPLC.

Ceftriaxone sodium is a widely used antimicrobial, which is only available as a lyophilized powder. The presence of methods for evaluating the quality of this product is very important and helps to ensure its effectiveness, in addition to contributing to the fight against bacterial resistance. Therefore, a clean and sustainable high-performance liquid chromatography (HPLC) method has been developed for evaluating ceftriaxone stability in pharmaceutical product. A Zorbax SB C18 (150 × 4.6 mm, 5 µm) column was maintained at 25°C; the mobile phase consisted of purified water acidified with 0.2% orthophosphoric acid and ethanol (87: 13, v/v) at a flow rate of 0.9 mL min-1. The detection wavelength was set at 260 nm. The method was linear over a concentration range of 20-120 µg mL-1, precise with relative standard deviations <2%, robust in the event of minor changes to the original method conditions, accurate with recovery between 98% and 102% and specific to degradation products. The retention time for ceftriaxone sodium was ~4.6 minutes. This work shows an ecologically correct option by HPLC method for the evaluation of ceftriaxone sodium in pharmaceutical product, as well as its stability, which addresses the requirements of the current green and sustainable analytical chemistry.

Evaluation of preservative effectiveness of liquid crystalline systems with retynil palmitate by the challenge test and D-value.

The objective of this work was to evaluate the preservative effectiveness of liquid crystalline systems containing retynil palmitate (RP) by the challenge test (CT) and D-value. A system was developed containing water, silicon glycol copolymer, and polyether functional siloxane with 1% RP added. The analyses were carried out by methods in the U.S. Pharmacopeia (USP 31, 2008) using the microorganisms Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger. The CT showed that after 7 days, all microorganisms were eliminated except A. niger, which maintained viability for at least 28 days after inoculation. Moreover, the microorganisms E. coli, P. aeruginosa, S. aureus, C. albicans, and A. niger presented different growth behaviors, evidenced by differences among the D-values calculated. It was concluded that the CT and D-value were efficient methods for evaluation of the preservative property of these formulations.

A New and Ecological Method to Quantify Vancomycin in Pharmaceutical Product by Infrared Spectrometry.

Vancomycin, an antimicrobial, does not present quantitative method by infrared spectrometry in the literature for the evaluation of a pharmaceutical product. This technique is considered a clean alternative because in the main, there is no solvent involved and the generation of waste is reduced. So, the aim of this study was to develop and validate a new, ecological, low cost and fast method by infrared spectrometry using KBr and band between 1450-1375 cm-1. It was linear in the range of 1.0-2.0 mg/150 mg, with a correlation coefficient of 0.9994. Selective when the spectra of vancomycin reference and sample were compared. Precise by repeatability (2.29%) and intermediate precision (3.12%). Accurate with average recovery of 99.37% and robust when strength and compression time of the pellets and KBr brand were varied. Considering all the methods found in literature, there is not one using infrared spectrometry for quantitative purpose, so the method developed and validated could be considered an innovation and clean alternative. This is due to the fact that it is fast, easy to handle, low cost, and non-toxic as well as generating minimal waste. The method can be applied in the routine analysis of vancomycin dosage form and is an important option for the current and sustainable pharmaceutical analysis.

Cephalothin: Review of Characteristics, Properties, and Status of Analytical Methods.

BACKGROUND: Cephalothin (CET), a first generation cephalosporin, is the most efficient cephalosporin against resistant microorganisms. Many studies found in literature and pharmacopeias propose analytical methods which are most commonly HPLC and microbiological assays. OBJECTIVE: This paper shows a brief review of analytical methods to quantify CET with a green analytical chemistry approach. METHOD: The research data were collected from the literature and official compendia. RESULTS: Most of the analytical methods to determine CET were performed by HPLC and agar diffusion in pharmaceuticals, blood, urine, or water. Other analytical methods were found, such as UV-Vis, iodometry, fluorimetry, IR/Raman, electrochemical, and others in less quantity. One important aspect is that these methods use organic and toxic solvents like methanol and acetonitrile and only about 4% of the methods found use water as solvent. CONCLUSIONS: Research about analytical methods for CET focusing on green analytical chemistry is of great importance and could optimize its analysis in pharmaceutical industries and help to guarantee the quality of the product. More than just the development of new techniques, it is possible to enhance the ones that already exist, applying the green analytical chemistry principles. In this way, it will be possible to reduce the environmental impacts caused by other analytical procedures. HIGHLIGHTS: This work shows a brief review of literature and pharmacopeias of analytical methods to quantify CET. Its quality control can be updated to meet the needs of current analytical chemistry and to fit into sustainable and eco-friendly analysis.

Turbidimetric Method: A Multi-Advantageous Option for Assessing the Potency of Ceftriaxone Sodium in Powder for Injection.

BACKGROUND: Ceftriaxone sodium, an antimicrobial used in parenteral form, does not have a microbiological method by turbidimetry described in the literature. For drugs from antimicrobial class, the existence of a microbiological method for assessing their potency is essential. Not only are the results from the physical-chemical methods enough, but microbiological analyzes are also necessary. OBJECTIVE AND METHODS: Thus, this paper reports the development and validation of an efficient, accurate, reproducible, fast, and low-cost microbiological assay by turbidimetry to quantify ceftriaxone sodium in powder for injection. Water was used as the diluent to prepare the ceftriaxone solutions. BHI broth as used as culture media for the growth of the S. aureus ATCC 6538 at 9%. RESULTS: The method was linear in the range of 100-196 µg/mL, selective against the sample adjuvants and the forced degradation test, precise (intraday RSD 4.53%, interday RSD 3.85% and between analysts tcalculated 0.14 < 2.23 tcritical), accurate with recovery of 100.33% and robust against minor changes in the volume of culture medium used, wavelength, incubation time, and inoculum concentration. CONCLUSIONS AND HIGHLIGHTS: The turbidimetric method developed in this paper is a convenient and valuable alternative to the routine quality control of ceftriaxone sodium in powder for injection, since it allows a reliable quantification and can be used to complement the physical-chemical analysis.

Miniaturized Microbiological Method to Determine the Potency of Rifaximin in Tablets.

BACKGROUND: Rifaximin, a semi-synthetic antimicrobial, does not present microbiological method described in official compendia, and there is a lack of literature on this topic. The quality control of antimicrobials is extremely important to evaluate the real potency of pharmaceutical products. OBJECTIVE: A miniaturized turbidimetric method for determining the potency of rifaximin in tablets was developed and validated by turbidimetry, according to the international guidelines. METHOD: Escherichia coli ATCC 10536 IAL 2393, brain heart infusion (BHI) broth, inoculum at 8%, rifaximin in purified water with 20% ethanol at 5, 10, and 20 µg/mL and 530 nm were used. RESULTS: The method was considered selective for rifaximin, as the adjuvants did not show activity; linear with correlation coefficients 0.9998 for standard and 0.9999 for sample; accurate with 99.73% recovery; precise with RSD less than 3%; and robust in the face of small variations in (i) rifaximin volume, (ii) proportion of ethanol, (iii) inoculum volume. CONCLUSIONS: The method is considered adequate and safe to evaluate the potency of rifaximin in tablets, contemplating speed, low cost, low waste generation, and ease of operation. HIGHLIGHTS: This work usescurrent, sustainable, and green analytical chemistry and can be used in the routine analyses of rifaximin by laboratories and the pharmaceutical industry around the world.

Eco-Friendly Pharmaceutical Analysis of Rifaximin in Tablets by HPLC-MS and Microbiological Turbidimetry.

Rifaximin, an antimicrobial used for the treatment of various diseases, lacks analytical methods in official compendia for evaluation of the final product. This paper presents an eco-friendly protocol for rifaximin tablets by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). The method was completely validated according to the International Conference on Harmonization guidelines and developed following the concept of Quality by Design. The separation was achieved using a C18 column, purified water +0.1% glacial acetic acid and ethyl alcohol, 52:48 (v/v), as mobile phase, 0.9 mL min-1 at 290 nm and ambient room temperature. Mass spectral analyses were performed using electrospray ionization (ESI) ion source and ion trap mass analyzer. The method was linear over the concentration range of 5-50 µg mL-1. The sample was subjected to acidic, basic, neutral, oxidative and photolytic degradation. Degradation products did not interfere in the quantification of the rifaximin, so the method can be considered indicative of stability. Degradation products were also evaluated individually by microbiological method using Escherichia coli. The validated method could be used promisingly as green analytical strategies for detection and quantification of rifaximin in tablets.

An Ecological and Miniaturized Biological Method for the Analysis of Daptomycin Potency.

BACKGROUND: Physicochemical and microbiological methods are found in the literature for the analysis of daptomycin, an antimicrobial. OBJECTIVE: This paper brings a miniaturized turbidimetric microbiological method for analysis of daptomycin in lyophilized powder. METHODS: The method was performed using 96-well microplates, 4-h incubation, 2, 4 and 8 µg/mL, 7% Staphylococcus aureus ATCC 6538 IAL 2082, and BHI broth. RESULTS: Linearity was proven by obtaining analytical curves with a correlation coefficient greater than 0.99 and statistical evaluation by ANOVA. The method was also selective, since the standard and sample analytical curves were parallel, proving that the excipient does not interfere with daptomycin analysis. Intraday, interday and inter-analyst precision presented RSDs of 2, 2.27, and 1.08%, respectively. Accuracy was assessed by the recovery test, where known quantities of standard solution are added to the sample and an average recovery value of 100.73% (RSD = 0.71%) was obtained. The present method was robust when minor changes were made in the parameters of used antimicrobial volume, inoculum volume and incubation time. CONCLUSIONS: This work is an innovative and ecological proposal and has advantages such as (i) less waste generation, (ii) miniaturized quantities of sample, culture media and inoculum, (iii) no need to use formaldehyde as in the traditional turbidimetric method, (iv) lower volume of glassware used and (v) shorter incubation time compared to other methods as agar diffusion requiring approximately 24 h. HIGHLIGHTS: This work is focuses on a current, innovative and sustainable theme for pharmaceutical analysis around the world.

A review of analytical techniques for determination of glimepiride: present and perspectives.

Glimepiride is an oral antidiabetic drug in the sulfonylurea class, which is widely used in treatment of Type 2 diabetes and it is currently available in more than 60 countries worldwide. As a result of the importance of this oral hypoglycemic agent in the treatment of noninsulin-dependent diabetes mellitus, this work aims to compile the published analytical methods reported so far in the literature for determination of glimepiride in biologic samples and pharmaceutical formulations. Techniques like high-performance liquid chromatography with ultraviolet, array-diode, mass spectroscopy, evaporative light scattering and charged aerosol detections, liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry, liquid chromatography-electrospray ionization-tandem mass spectrometry, semimicrobore high-performance liquid chromatography with column-switching, micellar electrokinetic chromatography, high-performance thin layer chromatography, polarography, and spectrophotometry have been used for analysis, from which it can be seen that high-performance liquid chromatography methods have been used most extensively.

Miniaturized turbidimetric assay: A green option for the analysis of besifloxacin in ophthalmic suspension.

Besifloxacin is an important antimicrobial agent, belonging to the class of fluoroquinolones, used in the treatment of infectious conjunctivitis. Quality control of this active pharmaceutical ingredient is essential, since poor quality antimicrobials may contribute to the aggravation of the worrying picture of bacterial resistance. Thus, analytical methods need to be developed, validated and improved for that purpose. It is also important that these methods be environmentally friendly, as ensuring the quality of products without harming the environment meets the global needs. The aim of the study was the development and validation of a miniaturized turbidimetric microbiological method for the analysis of besifloxacin hydrochloride (BSF) in ophthalmic suspension. The analyzes were performed in 96-well microplates using Staphylococcus epidermidis ATCC 12228 as test microorganism and BHI broth. The method was validated according to ICH guidelines and showed to be linear (in a range of 0.5-8.0 µg mL-1), precise, accurate, robust and selective. Study of photo-degradation kinetics of BSF sample showed a zero order reaction. A comparative study with a previously validated HPLC method showed that the methods are interchangeable. This work shows the great potential of the proposed method of being introduced in routine analyzes of quality control of BSF in ophthalmic suspension as an option in line with the principles of Green Chemistry.