ABSTRACT
Cyclodextrins (CDs) are cyclic oligosaccharides that contain a relatively hydrophobic central cavity and a hydrophilic outer surface. They are widely used to form non-covalent inclusion complexes with many substances. Although such inclusion complexes typically exhibit higher aqueous solubility and chemical stability than pure drugs, it has been shown that CDs can promote the degradation of some drugs. This property of stabilizing certain drugs while destabilizing others can be explained by the type of CD used and the structure of the inclusion complex formed. In addition, the ability to form complexes of CDs can be improved through the addition of suitable auxiliary substances, forming multicomponent complexes. Therefore, it is important to evaluate the effect that binary and multicomponent complexes have on the chemical and physical stability of complexed drugs. The objective of this review is to summarize the studies on the stabilizing and destabilizing effects of complexes with CDs on drugs that exhibit stability problems.
ABSTRACT
The freeze-thaw (F/T) method is commonly employed during the processing and handling of drug substances to enhance their chemical and physical stability and obtain pharmaceutical applications such as hydrogels, emulsions, and nanosystems (e.g., supramolecular complexes of cyclodextrins and liposomes). Using F/T in manufacturing hydrogels successfully prevents the need for toxic cross-linking agents; moreover, their use promotes a concentrated product and better stability in emulsions. However, the use of F/T in these applications is limited by their characteristics (e.g., porosity, flexibility, swelling capacity, drug loading, and drug release capacity), which depend on the optimization of process conditions and the kind and ratio of polymers, temperature, time, and the number of cycles that involve high physical stress that could change properties associated to quality attributes. Therefore, is necessary the optimization of F/T conditions and variables. The current research regarding F/T is focused on enhancing the formulations, the process, and the use of this method in pharmaceutical, clinical, and biological areas. The present review aims to discuss different studies related to the impact and effects of the F/T process on the physical, mechanical, and chemical properties (porosity, swelling capacity) of diverse pharmaceutical applications with an emphasis on their formulation properties, the method and variables used, as well as challenges and opportunities in developing. Finally, we review the experimental approach for choosing the standard variables studied in the F/T method applying the systematic methodology of quality by design.
ABSTRACT
This study aimed to identify variation in the minimum biocidal concentration (MBC) over time, comparing three commercial super-oxidized solutions with different chemical compositions. In the bactericidal assay, the following bacteria were tested: Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), and for each ATCC, one wild-type strain was used. In vitro experiments were performed in triplicate at 0, 60, and 120 days of follow up. A commercial formulation based on sodium and chloride ions (SCSS) was tested using a standard accelerated aging protocol. Data were analyzed with the Friedman and Wilcoxon signed-rank tests. The results showed that super-oxidized solution bases of 20 ppm of sodium (SSS) had a significant change in MBC at 120 days (p < 0.001), whereas SCSS remained stable during the same period (p = 0.18). However, after accelerated aging treatment, the MBC of SCSS increased (p < 0.001). With our proposed approach, the two SSS showed MBC variation at 120 days, whereas SCSS showed stability over time, similar to chlorhexidine, but lost its bactericidal properties after accelerated aging treatment.
Subject(s)
Sepsis , Anti-Bacterial Agents/pharmacology , Oxidation-Reduction , Time Factors , Sepsis/drug therapy , HumansABSTRACT
As a means to evaluate the potential of carrot anthocyanins as food colorants and nutraceutical agents, we investigated the physicochemical stability and antioxidant capacity of purple carrot extracts under different pH (2.5-7.0) and temperature (4-40 °C) conditions, in comparison to a commercial synthetic (E131) and a natural grape-based (GRP) colorant. During incubation, the colorants were weekly-monitored for various color parameters, concentration of anthocyanins and phenolics, and antioxidant capacity. Carrot colorants were more stable than GRP; and their thermal stability was equal (at 4 °C) or higher than that of E131 (at 25-40 °C). Carrot anthocyanins had lower degradation rate at low pH and temperature, with acylated anthocyanins (AA) being significantly more stable than non-acylated anthocyanins (NAA). Anthocyanins acylated with feruloyl and coumaroyl glycosides were the most stable carrot pigments. The higher stability of carrot colorants is likely due to their richness in AA and -to a lesser extent- copigmentation with other phenolics.
Subject(s)
Daucus carota , Food Coloring Agents , Anthocyanins/chemistry , Antioxidants/metabolism , Color , Daucus carota/chemistry , Food Coloring Agents/chemistry , Kinetics , Phenols/metabolism , Plant Extracts/chemistryABSTRACT
Touriga Nacional is a well-adapted Portuguese grape variety in São Francisco River Valley (northeastern Brazil). Nevertheless, it has only been indicated to short-term consumption because of the lack of chemical stability, which is attributed to low grape acidity and incomplete phenolic maturity. Therefore, we used Ultra-Performance Liquid Chromatography coupled High-resolution Mass Spectrometry, Nuclear Magnetic Resonance and chemometrics (PCA and PLS-DA) to evaluate the grape maturity and maceration time on chemical composition of wines from two harvest seasons. Moreover, we investigated how these experimental factors could affect their chemical stability. Grapes maturity showed to be the main effect. Overall, phenolic acids and short-chain organic acids were found to be at higher levels in wines produced with unripe grapes from February and shorter maceration time (p < 0.05). Proanthocyanidins and other flavonoids were increased in wines macerated for longer time using overripe grapes harvested in July. Furthermore, stable wines were made from overripe grapes, which contained more galacturonic acid.
Subject(s)
Vitis , Wine , Fruit/chemistry , Magnetic Resonance Spectroscopy , Proton Magnetic Resonance Spectroscopy , Vitis/chemistry , Wine/analysisABSTRACT
We report the first experimental investigation of porous organic cages (POCs) for the demanding challenge of SO2 capture. Three structurally related N-containing cage molecular materials were studied. An imine-functionalized POC (CC3) showed modest and reversible SO2 capture, while a secondary-amine POC (RCC3) exhibited high but irreversible SO2 capture. A tertiary amine POC (6FT-RCC3) demonstrated very high SO2 capture (13.78â mmol g-1 ; 16.4 SO2 molecules per cage) combined with excellent reversibility for at least 50 adsorption-desorption cycles. The adsorption behavior was investigated by FTIR spectroscopy, 13 Câ CP-MAS NMR experiments, and computational calculations.
ABSTRACT
BACKGROUND: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, which still has high prevalence worldwide. In addition, cases of drug resistance are frequently observed. In the search for new anti-TB drugs, compounds with antimycobacterial activity have been developed, such as derivatives of pyrazinoic acid, which is the main pyrazinamide metabolite. In a previous study, the compounds were evaluated and showed moderate antimycobacterial activity and no important cytotoxic profile; however, information about their pharmacokinetic profile is lacking. OBJECTIVE: The aim of this work was to perform physicochemical, permeability, and metabolic properties of four pyrazinoic acid esters. METHOD: The compounds were analyzed for their chemical stability, n-octanol:water partition coefficient (logP) and apparent permeability (Papp) in monolayer of Caco-2 cells. The stability of the compounds in rat and human microsomes and in rat plasma was also evaluated. RESULTS: The compounds I, II and IV were found to be hydrophilic, while compound III was the most lipophilic (logP 1.59) compound. All compounds showed stability at the three evaluated pHs (1.2, 7.4 and 8.8). The apparent permeability measured suggests good intestinal absorption of the compounds. Additionally, the compounds showed metabolic stability under action of human and rat microsomal enzymes and stability in rat plasma for at least 6 hours. CONCLUSION: The results bring favorable perspectives for the future development of the evaluated compounds and other pyrazinoic acid derivatives.
Subject(s)
Pyrazinamide/analogs & derivatives , 1-Octanol/chemistry , Animals , Cell Line , Drug Stability , Humans , Hydrogen-Ion Concentration , Microsomes, Liver/metabolism , Permeability , Pyrazinamide/chemistry , Pyrazinamide/pharmacokinetics , Rats , Water/chemistryABSTRACT
Geopropolis is a stingless bee product compose mainly by soil, presenting complex composition geopropolis has bioactive compounds that will depend on geographical characteristics as well bee species, changing their chemical and biological properties. Thus the study aims to evaluate the solubility and chemical stability of geopropolis extracts, through radical capture capacity and reducing capacity. Besides, analysis of free and bonded phenolic compounds, and mineral composition. Geopropolis samples of Melipona mondury, Melipona quadrifasciata, Melipona scutellaris, Melipona seminigra and Tetragonisca angustula were analyzed. Both reducing compounds with a maximum of 2.96% GAE and free radical scavenging potential with a maximum of 5.84% AAE and 8.58% TE increases over 30â¯days of storage time. Also, methanolic extracts released at least 51% more reducing compounds and exhibited at least 27% more free radical scavenging potential in comparison to ethanolic extracts. The polyphenolic profile shows 31 compounds after acid and alkaline hydrolysis as cinnamic acid, ferulic acid, p-coumaric acid, aromadendrin, vanillin. For the mineral composition, sixteen minerals were found among essential and non-essential, differentiating each sample by chemometric PCA and HCA analysis according to geographic region. Geopropolis is a potential source of natural compounds that could enhance food quality, increasing the bioactive content and preventing oxygen damages in foods, likewise for pharmacological application for healthcare.
Subject(s)
Polyphenols/analysis , Propolis/chemistry , Trace Elements/analysis , Animals , Antioxidants/analysis , Bees , Brazil , Propolis/analysisABSTRACT
This study was done to determine the time while the binary admixtures with midazolam and haloperidol drugs are administered by perfusion to the patients in the clinical routine. Samples with different concentrations of both drugs were prepared following the usual clinical practice. Solvents used were 0.9 % sodium chloride solution and 5% dextrose, and viaflo plastic bags were used as the containers of the admixtures. Samples were not protected from light and were stored at 20 ºC or at 4 ºC. Compatibility and physicochemical stability were studied by visual inspection, turbidity measurement, pH determination and ultraviolet detection high performance liquid chromatography (UV-HPLC) was used to determine midazolam and haloperidol concentrations. The assay was validated following the FDA and EMA guidelines. Darunavir was used as internal standard (IS). For the studied admixtures, turbidity measurements and pH determinations showed little changes in function of the time. Haloperidol and midazolam concentrations determined by HPLC are within the acceptable range of drug concentrations, which are considered stable for four days in case of admixtures stored at 20 ºC and for seven days for refrigerated admixtures. Taking into account the microbiological risk matrix, the compatibility and the chemical and microbiological stability of the midazolam and haloperidol in the co-administered admixtures in viaflo plastic bags with 0.9 % sodium chloride solution and 5% dextrose can be set as 48 hours when samples are stored at 20 ºC and one week if they are refrigerated.
Subject(s)
Midazolam/pharmacology , Haloperidol/pharmacology , Chromatography, High Pressure Liquid/methods , Hypnotics and Sedatives/administration & dosageABSTRACT
Norfloxacin, an antibiotic that exists in different solid forms, has very unfavorable properties in terms of solubility and stability. Binary complexes of norfloxacin, in the solid form C, and ß-cyclodextrin were procured by the kneading method and physical mixture. Their effect on the solubility, the dissolution rate, and the chemical and physical stability of norfloxacin was evaluated. To perform stability studies, the solid samples were stored under accelerated storage conditions, for a period of 6 months. Physical stability was monitored through powder X-ray diffraction, high-resolution 13C solid-state nuclear magnetic resonance, and scanning electron microscopy. The results showed evidence that the kneaded complex increased and modulated the dissolution rate of norfloxacin C. Furthermore, it was demonstrated that the photochemical stability was increased in the complex, without affecting its physical stability. The results point to the conclusion that the new kneading complex of norfloxacin constitutes an alternative tool to formulate a potential oral drug delivery system with improve oral bioavailability.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Norfloxacin/chemistry , Norfloxacin/metabolism , beta-Cyclodextrins/chemistry , beta-Cyclodextrins/metabolism , Biological Availability , Calorimetry, Differential Scanning , Drug Delivery Systems , Drug Stability , Magnetic Resonance Spectroscopy , Microscopy, Electron, Scanning , Sequestering Agents/chemistry , Sequestering Agents/metabolism , Solubility , X-Ray DiffractionABSTRACT
This work aimed at developing enalapril maleate granules in order to improve its stability in solid dosage form. Granules were prepared by hot melt granulation using a fluidized bed apparatus. Gelucire 50/13®, polyethylene glycol 6000 e Poloxamer 407® were studied and compared as binders in 2 × 2 factorial designs where the proportions of enalapril maleate, binders and spray dried lactose were varied. The granulation process resulted in high yields and granule sizes that indicated the prevalence of particles coating. Furthermore, the granules obtained showed adequate flowability and a fast dissolution rate of enalapril maleate with almost 100% of the drug released in 10 min. The stability of enalapril maleate in hard gelatin capsules showed that the drug stability was greatly increased in granules, since for raw drug, the remaining content of enalapril maleate after 91 days was 68.4% and, for granules, the content was always above 93%. This result was confirmed by the quantification of the degradation products, enalaprilat and diketopiperazine, which were found in very low content in granules samples. The results demonstrate that fluidized bed hot melt granulation with hydrophilic binders is a suitable alternative for improving the chemical stability of enalapril maleate.
Subject(s)
Enalapril/chemistry , Technology, Pharmaceutical , Drug StabilityABSTRACT
ABSTRACT Guava (Psidium guajava L.) is a native fruit of the American tropics with commercial applications for its taste, flavor and aroma. Numerous pharmacological uses have been described for it, such as the antiseptic effect of its leaves, the use of the fresh fruit and tea from its leaves for the treatment of diarrhea, dysentery, diabetes mellitus, and others. However, considering its rich composition, the guava also is a potential source of antioxidants to be used in the development of new formulations for cosmetic and/or dermatological applications, the main focus of this research. Herein, we describe the study of the phytochemical composition and the antioxidant activity of a guava extract prepared with non-toxic solvents aiming its use at biological applications. High performance liquid chromatography and mass spectrometry were employed to identify the major components, while thermoanalytical measurements and hot stage microscopy were used to assess the chemical stability of guava fruit extract. The antioxidant activity was also evaluated assessing the SOD-like activity and ABTS free radical scavenger. The results show that the extract is a rich source of phenolic compounds, such as quercetin, kaempferol, schottenol, among many others. All of the components found in guava extract exhibit biological effects according to the literature data, mainly antioxidant properties.
Subject(s)
Psidium/chemistry , Dermatology/classification , Phytochemicals/analysis , Antioxidants/analysis , Plant Extracts/pharmacology , Chromatography, High Pressure Liquid/instrumentation , Cosmetics/classificationABSTRACT
ABSTRACT This study was to develop, characterize, and evaluate the physical-chemical stability, in vitro antioxidant activity and in vitro safety profile of liquid crystalline systems (LCS) and microemulsions (MEs) with and without organic cocoa (OC) extract. LCS stabilized by surfactant polyoxyethylene 20 cetyl ether, containing water and oleic acid were studied. LCS and MEs were characterized using polarized light microscopy, small angle X-ray scattering, rheology and in vitro bioadhesion, and were evaluated for a period of 30 days by visual aspects, centrifuge test, pH value and relative density. PLM and SAXS assays showed the presence of domains of MEs, cubic and hexagonal mesophasephases, varying the proportions of the components of the formulations; where in the addition of the extract did not change rheological behavior of the formulations. All of the formulations were stable in the period analyzed and presented higher bioadhesive strength. In vitro antioxidant activity suggests that LCS and MEs presented a high capacity to maintain the antioxidant activity of OC extract. The results showed that the incorporation of OC in LCS improved the safety profile, according to cytotoxicity assays of systems may be a promising platform to OC extract for topical application for the potential treatment of skin disorders.
Subject(s)
Surface-Active Agents , Liquid Crystals/analysis , Skin , Cacao/adverse effects , Drug Delivery Systems , Microscopy, Polarization/methodsABSTRACT
Hydrophobic metal-organic frameworks (MOFs) not only have high water stability, but also exhibit high adsorption capacity towards organic molecules, in particular hydrocarbons. Herein we report a rare metal fluoride organic framework MFOF-1 with high hydrophobicity, which is constructed from unprecedented fluoride- and sulfate-bridged cubane-type tetranuclear cobalt clusters. MFOF-1 consists of three types of polyhedral cages with face-sharing configurations, and possesses a novel (3,9)-connected 3D+3Dâ3D self-interpenetrating array or the rare pyr topology. MFOF-1 shows high thermal stability and high stability in water and even acid/base aqueous solutions, and exhibits rather high H2 and CO2 storage capacities at ambient pressure. Remarkably, MFOF-1 shows little adsorption of water but considerably high uptakes of methanol, n-hexane, cyclohexane, and benzene, and exhibits a certain degree of adsorption selectivity of benzene over cyclohexane.
ABSTRACT
Our aim in this study was to evaluate how the chemical stability of silver nanoparticles (SNs) influences their efficacy against Candida albicans and C. glabrata biofilms. Several parameters of SN stability were tested, namely, temperature (50ºC, 70ºC, and 100ºC), pH (5.0 and 9.0), and time of contact (5 h and 24 h) with biofilms. The control was defined as SNs without temperature treatment, pH 7, and 24 h of contact. These colloidal suspensions at 54 mg/L were used to treat mature Candida biofilms (48 h) formed on acrylic. Their efficacy was determined by total biomass and colony-forming unit quantification. Data were analyzed using analysis of variance and the Bonferroni post hoc test (α = 0.05). The temperature and pH variations of SNs did not affect their efficacy against the viable cells of Candida biofilms (P > 0.05). Moreover, the treatment periods were not decisive in terms of the susceptibility of Candida biofilms to SNs. These findings provide an important advantage of SNs that may be useful in the treatment of Candida-associated denture stomatitis.
Subject(s)
Antifungal Agents/pharmacology , Biofilms/drug effects , Candida albicans/drug effects , Candida glabrata/drug effects , Dentures/microbiology , Nanoparticles , Silver/pharmacology , Acrylates , Biomass , Candida albicans/physiology , Candida glabrata/physiology , Colony Count, Microbial , Humans , Hydrogen-Ion Concentration , Temperature , Time FactorsABSTRACT
PURPOSE: Solid-lipid microparticles loaded with high amounts of the sunscreen UV filter benzophenone-3 were prepared by spray congealing with the objective of decreasing its skin penetration and evaluate whether the sunscreen's photoprotection were impaired by the microencapsulation process. METHODS: The microparticles were produced using the natural lipids carnauba wax or bees wax and three different concentrations of benzophenone-3 (30, 50 and 70%) using spray congealing technique. RESULTS: The microparticles presented properties suitable for topical application, such as spherical morphology, high encapsulation efficiency (95.53-102.2%), average particle sizes between 28.5 and 60.0 µm with polydispersivities from 1.2 to 2.5. In studies of in vitro skin penetration and preliminary stability, formulations of gel cream containing carnauba wax solid lipid microparticles and 70% benzophenone-3 when compared to the formulation added of bees wax solid-lipid microparticles containing 70% benzophenone-3, was stable considering the several parameters evaluated and were able to decrease the penetration of the UV filter into pig skin. Moreover, the formulations containing solid lipid microparticles with 70% benzophenone-3 increased the photoprotective capacity of benzophenone-3 under UV irradiation. CONCLUSION: The results show that spray-congealed microparticles are interesting solid forms to decrease the penetration solar filters in the skin without compromising their photoprotection.
Subject(s)
Benzophenones , Lipids , Skin Absorption , Skin/metabolism , Sunscreening Agents , Ultraviolet Rays/adverse effects , Waxes , Animals , Benzophenones/chemistry , Benzophenones/pharmacokinetics , Benzophenones/pharmacology , Capsules , Cell Line , Lipids/chemistry , Lipids/pharmacokinetics , Lipids/pharmacology , Mice , Sunscreening Agents/chemistry , Sunscreening Agents/pharmacokinetics , Sunscreening Agents/pharmacology , Swine , Waxes/chemistry , Waxes/pharmacokinetics , Waxes/pharmacologyABSTRACT
The purpose of this study is to develop and improve oral liquids formulations of sildenafil citrate for paediatric use. Four different formulations were developed, which are as follows: two aqueous solutions of sildenafil citrate (2.5 mg/mL), with or without preservatives, and two other solutions of sildenafil in simple syrup (1.25 mg/mL), with or without preservatives. All of the formulations were physically, chemically and microbiologically stable for three months. The results of the stability studies allowed for the optimisation of formulations without preservatives due to their simplicity and their similar stable conditions when compared to the formulations containing antimicrobials. The shelf life of both formulations was three months; however, upon opening, aqueous solutions should be used within 10 days and kept refrigerated, and syrup solutions should be used within 14 days in a hospital setting.
O objetivo deste trabalho é desenvolver e otimizar formulações líquidas orais de citrato de sildenafil adequadas ao uso pediátrico. Foram desenvolvidas quatro formulações diferentes: duas soluções aquosas de citrato de sildenafila (2,5 mg/mL) com ou sem conservantes e duas soluções de citrato de sildenafil em xarope simples (1,25 mg/mL) com ou sem conservantes. Todas as formulações desenvolvidas apresentaram estabilidade quer físico-química quer microbiológica durante 3 meses. Os resultados dos estudos de estabilidade permitiram otimizar as formulações isentas de conservantes, uma vez que estas eram mais simples e apresentavam do mesmo modo uma boa estabilidade, comparando com as formulações que continham conservantes. O período de utilização de ambas as formulações é de três meses, no entanto, após abertura do frasco, a solução aquosa deve ser utilizada durante 10 dias, acondicionada no refrigerador e o xarope deve ser utilizado durante 14 dias, mesmo em ambiente hospitalar.
Subject(s)
Chemistry, Pharmaceutical/methods , Sildenafil Citrate/pharmacokinetics , Child Health/classificationABSTRACT
Oral Candidiasis is an opportunist fungal infection, with high incidence in HIV and immunosuppressed patients and Candida albicans is the most common causing agent. In some cases, it can evolve to resistant injuries to antifungal conventional therapy. According to Brazilian Homeopathic Pharmacopeia (BHP) [1], biotherapic medicines are prepared from chemically undefined biological products. Biotherapics created by Brazilian doctor Roberto Costa (RC) have a different homeopathic compounding technique, as its dynamization starts from the ethiologic agent of the illness in its alive form, which present higher capability to stimulate the host immunological system [2,3].Further experiments are being carried out in order to confirm the preliminary data obtained.(AU)
Subject(s)
Candida albicans , Candidiasis, Oral , BiotherapicsABSTRACT
Introdução: O sucesso da terapia endodôntica está condicionado adiversos fatores, entre os quais o uso de substâncias químicas deboa qualidade. Objetivo: Neste trabalho investigaram-se algumascaracterísticas das soluções de hipoclorito de sódio utilizadas emclínicas de atendimento, tais como concentração, pH e armazenagem.Material e métodos: Para isso, distribuiu-se formulário com perguntasrelativas à solução empregada a 100 endodontistas, além de pedir-lhes100 ml do produto. As amostras foram levadas ao laboratório paraanálise por titulometria da concentração de cloro residual livre, bemcomo do pH das soluções, com o auxílio de um peagômetro. Resultados:Apenas 1% dos profissionais conhece o valor do pH das soluções. Dasamostras recolhidas, 36% apresentaram pH 9, 22% pH 10, 16% compH 13, 14% pH 12, 11% pH 11 e 1% pH 8. Quanto aos profissionais,37% mantinham seus frascos sob refrigeração e 67% em temperatura ambiente. Conclusão: Os endodontistas usam soluções de hipocloritode sódio diferentes daquelas que desejam por desconhecerem ascondições necessárias para a manutenção da estabilidade química.
Introduction: The success of endodontic therapy is conditioned byseveral variables, being the use of good quality chemical agents one ofthem. Objective: In this study, some characteristics of commonly usedsodium hypochlorite irrigants were investigated, such as: concentration,pH, and storage conditions. Material and methods: For this purpose, aquestionnaire comprising questions regarding the employed irrigant wassent to 100 endodontists. Besides that, a 100mL sample of the sodiumhypochlorite irrigant used by them was collected. Free residual chlorinedetermination was laboratorially carried out through titration method.Additionally, pH was measured, through peagameter reading. Results:Only 1% of the professionals did know the pH value of the solutionsused by them. Concerning to pH value, 36% of the solutions presentedpH 9; 22%, pH 10; 16%, pH 13; 14%, pH 12; 11%, pH 11; and 1%, pH8. 37% of the endodontists kept the solution flasks under refrigeration,and 67% kept them at environmental temperature. Conclusion: It can beconcluded that the endodontists are using altered hypochlorite solutionsbecause they fail to observe the necessary conditions for maintainingthe solution?s chemical stability.
ABSTRACT
Accelerated stability tests are indicated to assess, within a short time, the degree of chemical degradation that may affect an active substance, either alone or in a formula, under normal storage conditions. This method is based on increased stress conditions to accelerate the rate of chemical degradation. Based on the equation of the straight line obtained as a function of the reaction order (at 50 and 70 ºC) and using Arrhenius equation, the speed of the reaction was calculated for the temperature of 20 ºC (normal storage conditions). This model of accelerated stability test makes it possible to predict the chemical stability of any active substance at any given moment, as long as the method to quantify the chemical substance is available. As an example of the applicability of Arrhenius equation in accelerated stability tests, a 2.5 percent sodium hypochlorite solution was analyzed due to its chemical instability. Iodometric titration was used to quantify free residual chlorine in the solutions. Based on data obtained keeping this solution at 50 and 70 ºC, using Arrhenius equation and considering 2.0 percent of free residual chlorine as the minimum acceptable threshold, the shelf-life was equal to 166 days at 20 ºC. This model, however, makes it possible to calculate shelf-life at any other given temperature.
Testes acelerados de estabilidade são indicados para avaliar, em um curto período de tempo, o grau de degradação química que poderá afetar uma substância química, isoladamente ou quando inserida em uma fórmula, sob condições normais de armazenamento. Este método está fundamentado na intensificação das condições de estresse para acelerar a velocidade de degradação química. Baseando-se na equação da reta obtida e na ordem de reação determinada (a 50 e 70 ºC) e usando a equação de Arrhenius, a velocidade de reação foi calculada para a condição de temperatura de 20ºC (condições normais de armazenamento). Este modelo de teste acelerado de estabilidade torna possível a predição da estabilidade química de qualquer substância, em qualquer tempo, desde que o método de quantificação da substância química esteja disponível. Como exemplo da aplicabilidade da equação de Arrhenius em teste acelerado de estabilidade, uma solução de hipoclorito de sódio a 2,5 por cento foi analisada por ser quimicamente instável. A quantificação do cloro residual livre foi determinada através de titulação iodométrica. A partir dos dados obtidos decorrentes das amostras submetidas às temperaturas de 50 e 70 ºC e com o emprego da equação de Arrhenius, o tempo de prateleira obtido foi de 166 dias em temperatura de 20 ºC, considerando como limite inferior a concentração de 20 mg/mL de cloro residual livre. Este modelo, entretanto, possibilita o cálculo de tempo de prateleira em qualquer outra temperatura de interesse.