Tools to Evaluate the Eco-efficiency of Analytical Methods in the Context of Green and White Analytical Chemistry: A Review.

BACKGROUND: The release of a product in the consumer market requires an analysis by quality control. This sector makes use of reliable analytical methods, by high performance liquid chromatography (HPLC), spectrophotometry in the ultraviolet and visible regions (UV-Vis), spectrophotometry in the infrared region (IR) or thin layer chromatography (TLC), for example, to reach a result. The analysis conditions of most of these analytical methods currently still use toxic reagents, generate a greater amount of waste, sample preparation has more steps, the need for instrumentation and consumables in greater quantity, generating a cost and impact on health and the environment greater than if there were adoption of the Green Analytical Chemistry (GAC) and the White Analytical Chemistry (WAC). OBJECTIVE/METHODS: The objective of this review is to show the relationship of analytical choices for current pharmaceutical analyzes with the GAC and the WAC. RESULTS: Analytical methods can be evaluated for greenness and whiteness using tools such as the National Environmental Method Index (NEMI), Eco-Scale Assessment (ESA), Analytical Greenness Metric (AGREE) and Green Analytical Procedure Index (GAPI). CONCLUSION: The use of NEMI, ESA, AGREE and GAPI tools brings the objective evidence needed to discuss the greenness and whiteness of an analytical method, leaving the subjective level. Furthermore, semi or quantitative data facilitate the choice of an analytical method and its conditions, when the target is the concern with eco-efficiency.

Review of Analytical Methods for Evaluating Azithromycin in the Context of Green Analytical Chemistry.

BACKGROUND: Azithromycin (AZT) is an antimicrobial available in different pharmaceutical forms and many people can have access to this medicine. Therefore, the existence of adequate and reliable analytical methods for evaluating the quality of AZT and AZT-based products is essential. OBJECTIVE/METHODS: The purpose of this review is to discuss the analytical methods for evaluating AZT present in the literature and official compendia in the context of Green Analytical Chemistry (GAC). RESULTS: Among the methods found in the literature for evaluating AZT, the most used method is HPLC (62%) followed by TLC (14%) and the microbiological method by agar diffusion (14%). Even pharmacopoeias recommend the analysis of AZT by HPLC or agar diffusion. Acetonitrile and methanol account for 35% of the most used solvents in the analyses, followed by buffer. CONCLUSION: AZT lacks analytical methods in the context of GAC. Both physical-chemical and microbiological methods can contemplate the environmentally friendly way to analyze AZT and AZT-based products, depending only on the chosen conditions. Ethanol, purified water, acetic acid instead of methanol, acetonitrile, buffer, formic acid in the physical-chemical methods are excellent alternatives. However, in the microbiological method, turbidimetry is a great option instead of agar diffusion.

Green Method for Evaluation of Marbofloxacin Tablets by HPLC and Evaluation of Interchangeability With UV and Turbidimetric Methods.

BACKGROUND: Marbofloxacin (MAR) is a veterinary antimicrobial, marketed in injectable solution, oral suspension, and tablets. MAR has no monograph for tablet evaluation in official compendiums. High Performance Liquid Chromatography (HPLC) methods present in the literature for evaluating MAR in tablets do not follow the principles of green and sustainable analytical chemistry. OBJECTIVE: A green, clean, and sustainable method by HPLC was developed and validated to evaluate the content and stability of MAR in tablets, in addition to comparing it with other methods available in the literature. METHOD: A C8, 5 µm, 4.6 × 150 mm (ACE®) column, purified water with 0.2% formic acid-ethanol (70:30, v/v) as the mobile phase, and a flow rate of 0.7 mL/min at 296 nm were used. RESULTS: The method was linear over a concentration range of 1-10 µg/mL, selective for tablet matrix and forced degradation, precise with relative standard deviations (RDS) less than 5%, accurate with recovery of 99.99%, and robust to changes in the mobile phase, flow rate, wavelength, equipment, and column brand. The retention time for MAR was approximately 3.1 min. CONCLUSIONS: The method can be used in routine analysis of MAR in tablets in chemical-pharmaceutical laboratories. Furthermore, it can be used to verify the stability of MAR-based products and proved to be interchangeable with spectrophotometric method in the UV region and turbidimetric microbiological method. HIGHLIGHTS: A green method for evaluation of marbofloxacin tablets by HPLC was developed and validated. Additionally, it has been shown to be interchangeable with UV and turbidimetric methods.

Moxifloxacin: Physical-chemical and Microbiological Analytical Methods in the Context of Green Analytical Chemistry.

Moxifloxacin (MOX) is a fourth-generation fluoroquinolone used in the form of tablets, infusion solutions and ophthalmic solutions. It does not have a physical-chemical or microbiological analytical method described in an official compendium. However, the literature shows some analysis methods for pharmaceuticals and biological matrices. In this context, the objective is to show the analytical methods present in the literature for the investigation of MOX by physical-chemical and microbiological techniques, as well as discussing them according to the requirements of current pharmaceutical analyses and green analytical chemistry. Among the physical-chemical methods present in the literature for MOX evaluation, 33% are HPLC, 21% are UV-Vis and 17% are capillary electrophoresis. On the other hand, among the microbiological methods, all of them are based on diffusion in agar. There is still scope in the literature to incorporate new and improved analytical methods for MOX evaluation, which adopt the concepts of green and sustainable analytical chemistry, either by using less (or not using) toxic organic solvents, reducing waste generation or even reducing the analysis time according to the intended objectives.

Cyclodextrin inclusion complex of a multi-component natural product by hot-melt extrusion.

This study aimed to investigate whether hot-melt extrusion (HME) processing can promote molecular encapsulation of a multi-component natural product composed of volatile and pungent hydrophobic substances (ginger oleoresin (OR)) with cyclodextrins. 6-Gingerol and 6-shogaol, the biomarkers of ginger OR, were quantified by HPLC. Phase-solubility studies were performed using ß-cyclodextrin (ßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) for ginger OR complexation. Solid complexes were then prepared by thermal (HME)- and solvent (slurry (SL))-based methods. Morphology, thermal behavior, solubility, in vitro dissolution, and in vivo anti-inflammatory activity were evaluated. HPßCD gave rise to AL-type complexes with ginger OR, whereas ßCD led to materials with limited solubility. Ginger OR was complexed with HPßCD by HME without significant change in gingerol and shogaol content. Additionally, thermogravimetric analysis (TGA) suggested higher volatile retention in HME complexes than in SL ones. Shogaol and gingerol solubility and dissolution significantly increased from SL and HME complexes compared with ginger OR. In turn, 1:2 OR/HPßCD HME complex showed higher 6-shogaol solubility than SL, associated with a gradual release. The carrageenan-induced pleurisy test showed that the anti-inflammatory activity of ginger OR was maintained after complexation with HPßCD. The complexes significantly decrease the levels of IL-1ß and inhibit cell migration. HME complex showed performance equivalent to the positive control and superior to the SL material. Taken together, these results indicate that HME can be useful for promoting the molecular encapsulation of complex natural products that contain volatile and thermolabile substances. HME complexes showed better in vivo and in vitro performance than complexes prepared using the solvent-based method.

Overview of Analytical Methods for Evaluating Tinidazole.

BACKGROUND: Tinidazole (TIN) has amoebicidal, giardicidal, antifungal, and antimicrobial activities. It is marketed in the form of tablets. Analytical methods to assess the quality of TIN-based products are essential for correct pharmacotherapy. OBJECTIVE: The objective of this review is to show an overview of the existing analytical methods for evaluating TIN, according to the quality control (QC) analysis routine and green analytical chemistry (GAC). RESULTS: Official compendia show a method for evaluating TIN in tablets by nonaqueous titration, which has limitations (materials on the mg scale using solvents considered not recommended and harmful). The literature shows some analytical methods for evaluating TIN, both physicochemical and microbiological. The most used physicochemical method is UV (41%), and second is HPLC (28%). Among the microbiological methods, agar diffusion and turbidimetric methods are equally divided. The most studied matrix is TIN tablets (73%), and the most used solvent is methanol. CONCLUSIONS: The literature shows space for the development of analytical methods according to GAC for evaluating TIN, optimizing time, resources, and materials, reducing waste generation, and opting for less aggressive reagents, solvents, and diluents. HIGHLIGHTS: This review shows the status of analytical methods, both physicochemical and microbiological, for the analysis of TIN in pharmaceutical matrix, in the context of routine analysis of the chemical-pharmaceutical industries and of GAC.

Fast and New Microbiological Method for Evaluating the Potency of Marbofloxacin-Based Tablets.

BACKGROUND: Marbofloxacin (MAR) is an antimicrobial belonging to the fluoroquinolone class and is marketed in the form of tablets. There is no microbiological monograph in official compendia to evaluate the potency of the final product. Furthermore, the literature is scarce in this context. OBJECTIVE: The objective is to develop and validate a microbiological method by turbidimetry to evaluate the potency of MAR-based tablets, based on the principles of green analytical chemistry. METHODS: Purified water-ethanol (9 + 1, v/v) was used as diluent to prepare the MAR solutions at concentrations of 0.25, 0.8, and 2.56 µg/mL, brain heart infusion (BHI) broth as culture media, E. coli American Type Culture Collection (ATCC) 25922 at 10% and incubation in a shaker at 37°C for 4 h were used in the method. RESULTS: The method was: linear in the range of 0.25 to 2.56 µg/mL; selective against the sample adjuvants; precise (intra-day RSD 2.26%, inter-day RSD 3.49%, and inter-analyst RSD 3.59%); accurate with a recovery of 100.20%; and robust against changes in culture medium volume in the tube, shaker rotation, and incubation temperature in the shaker. The potency of MAR tablets was 96.98% using the proposed method. CONCLUSION: The turbidimetric method developed is a new, fast, and optimized option to the routine QC of MAR in tablets, since it allows the evaluation of the drug's potency in the final product and can be used to complement the results of the physicochemical analysis, in addition to being a green and sustainable alternative. HIGHLIGHTS: The work shows an ecological and green alternative to the routine microbiological pharmaceutical analysis of MAR tablets.

Status of Physicochemical and Microbiological Analytical Methods of Gatifloxacin: A Review.

BACKGROUND: Gatifloxacin (GAT), an antimicrobial of the fourth generation of fluoroquinolones, has a broad spectrum of action with activity against Gram-positive and Gram-negative, aerobic and anaerobic organisms, including mycobacteria. OBJECTIVE: The objective of this review is to discuss about (i) characteristics, (ii) properties, and (iii) analytical methods of gatifloxacin. RESULTS: Among the methods described in the literature for the evaluation of GAT, the most frequent was HPLC (50%) for both the analysis of pharmaceutical and biological matrixes. GAT has no monograph described in official compendia. Methods for evaluating GAT in pharmaceutical matrixes were the most found in the literature, 79%. Acetonitrile (42%), methanol (20%), and buffer solution (16%) were the most used diluents. GAT, being an antimicrobial, must be analyzed by physical-chemical and microbiological methods, since the evaluation of potency is essential. In this context, the literature is scarce (4%). CONCLUSIONS: There is a gap in the literature for environmentally friendly methods for evaluating GAT. Faster, more optimized and dynamic microbiological methods, as well as physicochemical methods, use less aggressive solvents with fewer steps and less waste. Currently, pharmaceutical analyses require reliable analytical methods, but also safe for both the analyst and the environment. HIGHLIGHTS: This review shows the status of analytical methods, both physicochemical and microbiological, for the analysis of GAT in pharmaceutical and biological matrixes, also addressing its context in green and sustainable analytical chemistry.

Eco-Friendly UV Spectrophotometric Method for Evaluation of Marbofloxacin in Tablets: Stability Study.

BACKGROUND: Marbofloxacin (MAR) is an antimicrobial for veterinary use, and it does not have a monograph in an official compendium for the pharmaceutical form in tablets. OBJECTIVE: In this context, the objective of this work was to develop and validate an effective, eco-friendly, and indicative of stability method by spectrophotometry in the ultraviolet region (UV) for quantitative evaluation of MAR in tablets. METHOD: Purified water-ethanol (80:20, v/v) as a diluent, quartz cubette and 296 nm were used. RESULTS: The method was linear in the range of 3-9 µg/mL (0.9994) with detection and quantification limits of 0.39 and 1.18 µg/mL, respectively, selective in the comparison of standard and sample, precise in intraday (RSD 1.20%), interday (RSD 1.68%), and between analysts (RSD 3.26%) levels, exact with average recovery of 100.39% and robust against small changes in wavelength, diluent concentration, and the use of the ultrasound device. The forced degradation test (sample solutions prepared in 0.1 M HCl, 0.1 M NaOH, and neutral conditions and kept at 60°C during 2 h, and exposure to UV 254 nm lamp at ambient temperature during 2 h) showed that the proposed method is able to assess the susceptibility of MAR. CONCLUSIONS: The method can be reliably applied in routine analysis of MAR in tablets as well as being stable, eco-friendly, effective, accessible, and following the principles of green analytical chemistry. HIGHLIGHTS: MAR, an antimicrobial for veterinary use, does not have a monograph in an official compendium for final product evaluation. The use of MAR-based products with inadequate quality can leave residues in foods of animal origin and can also contribute to microbial resistance. So, an ecologically correct and reliable method was developed to evaluate MAR in a final product.

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.

An Overview of Analytical Methods for the Quantification of Marbofloxacin in Pharmaceutical, Biological, and Food Matrixes.

BACKGROUND: Marbofloxacin (MAR), a second-generation fluoroquinolone, is used in veterinary medicine in the form of tablets. It has a broad spectrum of action, low toxicity, and limited development of bacterial resistance. The analytical methods available in the literature become more important since MAR in tablets does not have a monograph in official compendiums. OBJECTIVE: Our purpose is to review the methods according to the analyzed matrix and place them according to the conditions used in the scope of green analytical chemistry, in addition to discussing possible gaps and opportunities for the development of new methods. RESULTS: MAR, being an antimicrobial, presents both physicochemical (93%) and microbiological (7%) methods in the literature. Among the methods found, 53% are for analysis of food matrixes using preferably HPLC and TLC-MS, 27% are for analysis of biological matrixes and 20% are for analysis of pharmaceutical matrixes, and in both HPLC is preferably used. CONCLUSION: Therefore, there is still a gap in the literature in relation to other analytical methods for the analysis of MAR, which are faster, such as microbiological turbidimetry, sustainable, such as miniaturized methods, and ecologically correct, such as those that do not use toxic organic solvents. HIGHLIGHTS: A review of the analytical methods available in the literature for assessing the quality of MAR and MAR-based products in which the methods, as well as new opportunities for analysis according to green analytical chemistry, were described and discussed.

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.

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.

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.

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.

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.

Determination of dexamethasone acetate in CETETH 20-based in liquid crystalline systems using HPLC.

Dexamethasone acetate (DEX), a potent anti-inflammatory, is used primarily in the treatment of inflammatory and autoimmune diseases. It was incorporated in CETETH 20 (polyoxyethylene 20 cetyl alcohol)-based liquid crystalline systems to enhance the purpose of the drug. Concomitant with the pharmaceutical technology performed, a HPLC method was developed and validated for the quantification of dexamethasone acetate in CETETH 20-based liquid crystalline systems for the evaluation of the drug in the new matrix. The method was performed using a C18 column with acetonitrile:methanol:water (35:35:30, v/v/v) as the mobile phase at a flow rate of 0.8 mL min-1 at 239 nm. The method was linear in the range of 1-25 µg mL-1 ; the limit of quantification and limit of detection were 0.05 and 0.16 µg mL-1 , respectively; the accuracy of the method was 99.92% (relative standard deviation < 1%), and it presented intra-day and inter-day precision with deviations less than 1%. In this context, the method was successfully used to determine the incorporation efficiency of DEX in CETETH 20-based liquid crystalline systems and can be easily used by pharmaceutical companies and laboratories around the world.

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.

Short-Stability Study of Rifaximin-Based Samples.

BACKGROUND: Rifaximin is an oral antimicrobial with a daily dose ranging from 600 to 800 mg. It is classified as Class IV in the Biopharmaceutic Classification System. Thus, rifaximin-based samples were developed by complexation to ß-cyclodextrin using a phase solubility diagram, and malaxation and decreasing particle size using wet milling. OBJECTIVE: Concomitant to the pharmaceutical technology, a stability studywas undertaken with the objective of verifying the integrity of the drug. METHODS: The stability of the new samples were studied for 6 months, without interruption, under controlled conditions of temperature and humidity in a climatic chamber. They were analyzed simultaneously by HPLC and microbiological turbidimetry at zero, 3, and 6 months. RESULTS: Two of the samples follow second reaction order and one follows zero reaction order. Microbiological analysis proved to be important in assessing the potency of rifaximin in one of the samples, and its results were more consistent than the results by HPLC. CONCLUSIONS: The rifaximin-based samples were stable under controlled temperature and humidity conditions and the physical-chemical and microbiological methods were able to evaluate their behavior during the 6-month study. HIGHLIGHTS: It is worth considering the development of these products, since the design process of formulation and pharmaceutical technology is financially more attractive than the development of new drugs that require high levels of investment in research and development, innovation of public policies, and regulatory actions.