RESUMO
Levodopa, (S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid, is still considered the gold standard treatment for Parkinson's disease. However, oral levodopa shows poor pharmacokinetics and its efficacy becomes problematic with the progression of the disease. Pulmonary delivery using the association of the polymers: chitosan, hyaluronic acid and HPMC, represents a novel approach to overcome this problem. A stability-indicating liquid chromatography method for the quantitative determination of levodopa microparticles for pulmonary delivery was developed as well as its photodegradation kinetics in solution. The developed and validated method was applied for the analyses of the novel formulation as well as for protocols of stability studies.
Assuntos
Antiparkinsonianos/administração & dosagem , Levodopa/administração & dosagem , Administração por Inalação , Antiparkinsonianos/química , Antiparkinsonianos/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Excipientes , Cinética , Levodopa/química , Levodopa/efeitos da radiação , Luz , Limite de Detecção , Nanopartículas , Soluções Farmacêuticas , Fotoquímica , Padrões de Referência , Reprodutibilidade dos Testes , Espectrofotometria UltravioletaRESUMO
A stability-indicating HPLC method for the determination of mianserin hydrochloride in coated tablets was developed and validated. Also, drug photodegradation kinetics and cytotoxicity were determined. Chromatographic analyses were performed in an Ace RP-18 octadecyl silane column (250 mm x 4.6 mm i.d., particle size 5 microm) maintained at ambient temperature (25 degrees C). The mobile phase was composed of methanol, 50 mM monobasic potassium phosphate buffer and 0.3% triethylamine solution adjusted to pH 7.0 with phosphoric acid 10% (85:15, v/v) in isocratic mode at a flow rate of 1.0 mL x min(-1). The performed degradation conditions were: acid and basic media with HCl 1.0 M and NaOH 1.0 M, respectively, oxidation with H2O2 3% and the exposure to UV-C light. No interference in the mianserin hydrochloride elution was verified by degradation products formed. Linearity was assessed and ANOVA showed non-significant linearity deviation (p > 0.05). Adequate results were obtained for repeatability, intermediate precision, accuracy and robustness. The photodegradation kinetics of mianserin hydrochloride was evaluated in methanol. The degradation of mianserin could be better described as zero order kinetic (r = 0.9982). The UV-C degraded samples of mianserin hydrochloride were also studied in order to determine the preliminary cytotoxicity in vitro against mononuclear cells.
Assuntos
Antidepressivos de Segunda Geração/análise , Antidepressivos de Segunda Geração/toxicidade , Mianserina/análise , Mianserina/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Técnicas In Vitro , Indicadores e Reagentes , Cinética , Metanol , Monócitos/efeitos dos fármacos , Fotólise , Reprodutibilidade dos Testes , Solventes , Comprimidos , Temperatura , Raios UltravioletaRESUMO
The degradation kinetics of the antibiotic telithromycin using a stability-indicating high-performance liquid chromatography (HPLC) method is demonstrated. The photodegradation is performed by UVC lamp-254 nm (15W), installed in a chamber internally coated with mirrors, where telithromycin solutions prepared from coated tablets are placed in quartz cells. To promote oxidation, the reaction between the telithromycin solution and 3% hydrogen peroxide solution is carried out. The kinetics parameters of order of reaction and the rate constants of the degradation are determined for both conditions. The degradation process of telithromycin can be described by first-order kinetics under both experimental conditions used in this study. The results reveal the photo and oxidation lability of the drug and confirm the reliability of HPLC method for telithromycin in the presence of its degradation products.
Assuntos
Antibacterianos/química , Cromatografia Líquida de Alta Pressão/métodos , Cetolídeos/química , CinéticaRESUMO
A new chemical structure, the 4,2',4",2'''-tetrahydroxy-6',6'''-dimethoxy-4'-O-4'''- bichalcone, named achyrobichalcone was isolated and identified from an Achyrocline satureioides spray-dried powder (SDP80). The thermal and photo stability of this new compound as well as that of the main polyphenols present in the spray dried powder, quercetin, luteolin, 3-O-metylquercetin and the corresponding kinetics of degradation are reported. In the long-term testing (30 +/- 2 degrees C/75 +/- 5% RH, 12 months), the total polyphenols contained in SDP80 demonstrated to be stable, remaining higher than 90% after a 12 month exposure. The photo stability testing revealed that all polyphenols were stable for 48 h when SDP80 was conditioned in amber or transparent flasks and exposed to UV-C radiation (light express LE UV, 254 nm, 30W). In contrast, when unprotected, the polyphenols demonstrated to be sensitive to both, thermal stress testing (80 +/- 2 degrees C), for 14 days and to UV-C radiation. Luteolin showed to be the most stable against UVC light and 3-O-methylquercetin against temperature. The achyrobichalcone demonstrated to be the more unstable against both, temperature and light. The kinetics of polyphenol thermal degradation (80 +/- 2 degrees C, 49 days) and photodegradation (UV-C radiation, 96 h) followed, 2nd and 1st order reaction, respectively.
Assuntos
Achyrocline/química , Chalconas/análise , Chalconas/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Dessecação , Estabilidade de Medicamentos , Etanol , Temperatura Alta , Cinética , Luz , Espectroscopia de Ressonância Magnética , Fenóis/análise , Fenóis/efeitos da radiação , Extratos Vegetais/análise , Pós , Padrões de Referência , SolventesRESUMO
Lemongrass volatile oil (LVO) is an important ingredient in cosmetics, presenting antimicrobial properties, in particular antifungal activity, and it is a promising raw material for the development of pharmaceutical products. However, its volatility and susceptibility to degradation are the major drawbacks for the use of Cymbopogon citratus oil in pharmaceutical compounding. Thus, the aim of this work was to develop and to characterize microparticles containing this oil viewing the stabilization of LVO. Two techniques of preparation were evaluated; spray drying and precipitation, and two encapsulation materials, beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were tested. The microparticles were characterized in terms of content of water, yield, percentage of inclusion, infrared spectroscopy. Morphology was evaluated by scanning electronic microscopy. Studies of stability were also conducted. The content of citral (neral and geranial), major component of the oil, present in microparticles was assayed by a validated HPLC method. The percentage of inclusion of LVO into the microparticles was 56-60% and 26-29% using beta-CD and HP-beta-CD, respectively. The results showed that the use of the beta-CD as encapsulant material was more efficient. Additionally, an increased inclusion of lemongrass oil was observed with the precipitation technique.
Assuntos
Nanopartículas , Óleos de Plantas/química , Terpenos/química , 2-Hidroxipropil-beta-Ciclodextrina , Química Farmacêutica , Dessecação , Estabilidade de Medicamentos , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Pós , Espectrofotometria Infravermelho , Volatilização , Água/análise , beta-Ciclodextrinas/químicaRESUMO
Nitazoxanide is a new broad-spectrum, antiparasitic drug agent. The photodegradation of nitazoxanide was studied in order to investigate the degradation kinetics of this drug. The analyses of the degraded samples were performed by a stability-indicating liquid chromatographic method. The degradation was carried out in acetonitrile with coated tablets or oral suspension powder in quartz cells under UVC light at 254 nm. The kinetics parameters, such as order of reaction, rate constants, half-life (t(1/2)), and the time when 90% of the drug original concentration was left, were determined. The photodegradation of nitazoxanide for both pharmaceutical formulations in acetonitrile solution shows a zero-order kinetics under the applied experimental conditions. The obtained results confirm the reliability of the chromatographic method for determining the kinetics run of nitazoxanide in the presence of its degradation products. The present study reveals the photolability of the drug in solution. Thus, appropriated photoprotection is recommended during the manipulation of the drug.
Assuntos
Antiparasitários/química , Química Farmacêutica , Cromatografia Líquida/métodos , Fotólise , Tiazóis/química , Estabilidade de Medicamentos , Cinética , Nitrocompostos , Pós , Comprimidos , Raios UltravioletaRESUMO
Pantoprazole sodium is a proton pump inhibitor, used in acid-related disorders, like peptic ulcers and gastroesophageal reflux. This drug is unstable in acid solution and in the presence of salts. The aim of this work was to study the photostability under UVC radiation of pantoprazole and to determine its kinetics. A methanol solution and the solid pantoprazole were evaluated by HPLC within 120 min and 10 days, respectively. The work was also dedicated to evaluate and compare the ability of microencapsulation in stabilizing pantoprazole after UVC radiation. Pantoprazole-loaded microparticles prepared by emulsification/solvent evaporation or spray drying were compared. Pantoprazole was encapsulated using Eudragit S100 or its blend with poly(epsilon-caprolactone) or HPMC. In methanol solution, pantoprazole was completely degraded after 120 min and presented zero-order kinetics with t1/2 of 6.48 min. In the solid form, after 10 days, pantoprazole concentration was reduced to 27% following zero-order kinetic. The microparticles prepared only with Eudragit S100 demonstrated an increase of the drug photostability. After 10 days of irradiation, 56 and 44% of the drug was stable when encapsulated by emulsification/solvent evaporation and spray drying, respectively. The use of polymer blends did not improve the pantoprazole photostability.
Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/química , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/química , Cromatografia Líquida de Alta Pressão , Dessecação , Composição de Medicamentos , Estabilidade de Medicamentos , Emulsões , Excipientes , Luz , Metanol , Nanopartículas , Pantoprazol , Tamanho da Partícula , Fotoquímica , Polímeros , Soluções , Solventes , Raios UltravioletaRESUMO
The flavonoids quercetin, 3-O-methylquercetin and luteolin play an important role in the anti-inflammatory activity of Achyrocline satureioides ethanol extracts when administered intraperitoneally. The present work describes the oral anti-inflammatory effect of quercetin and A. satureioides extracts and the role played by the solvent concentration, adjuvant and drying processes of freeze-drying (FD) or spray-drying (SD) on the effect. The best anti-edema effect was observed with 250 mg/kg body wt of the freeze-dried powder (FDP), prepared with 40% (v/v) ethanol (FDP40). In contrast, 250 mg/kg body wt of FDP80, prepared with ethanol 80% (ES80), did not significantly inhibit the carrageenan-induced rat paw edema. However, when ES80 was freeze-dried in the presence of polysorbate 80 (FDP80-P80) or spray-dried in the presence of colloidal silicon dioxide (CSD) and P80 (SDP80), both dried extracts became more active. Quercetin suspension in saline did not inhibit paw edema, but the mixture of quercetin with polysorbate 80 was effective in edema inhibition by the oral route. Aqueous extract (ESAQ), freeze-dried (FDPAQ, FDPAQ-P80) or spray-dried (SDPAQ) did not exhibit the edema-inhibition effect. Taken together, the results point to the following order of efficacy (at 4 h, for example): FDP40 > indomethacin > SDP40 > SDP80 = FDP80-80 > Quercetin-P80. Additionally, the FDP40, SDP40 (prepared from 40% v/v ethanol added of CSD) and SDP80 reduced the total leukocyte and polymorphonuclear cell migration in the pleural cavity.
Assuntos
Achyrocline , Anti-Inflamatórios não Esteroides/farmacologia , Edema/prevenção & controle , Fitoterapia , Extratos Vegetais/farmacologia , Quercetina/farmacologia , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Carragenina , Relação Dose-Resposta a Droga , Composição de Medicamentos , Edema/induzido quimicamente , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Polissorbatos/química , Quercetina/administração & dosagem , Quercetina/química , Quercetina/uso terapêutico , Ratos , Ratos Wistar , SolventesRESUMO
Thermal and the photo stabilities of an Achyrocline satureioides powder (SDP40) were evaluated in particular concerning the total polyphenol content as well as the main identified constituents quercetin, luteolin, 3-O-methylquercetin and caffeic acid. SDP40 presented good stability for nine months under normal storage conditions of 25 degrees C temperature and 60% relative humidity (RH). In accelerated term testing, 50 degrees C temperature and 90% RH and also in stress testing, 80 degrees C, caffeic acid and a non-identified constituent P3 were the most instable constituents. Luteolin and 3-O-methylquercetin were the most stable constituents. Quercetin presented an unusual behavior, improving its concentration after 1 month at 50 degrees C or 2 days at 80 degrees C exposition, followed by a decrease in its concentration. The hypothesis that this observation is related to the simultaneous decreasing of a non-identified peak P3 or to the hydrolysis of a non-identified precursor as a quercetin heteroside is being investigated. The SDP40 presented good stability against UV-C light when conditioned in amber or transparent containers, but it suffered degradation when stored in open-dishes. In summary, the total polyphenol content remains within acceptable limits of 10% under normal storage conditions for nine months. However, the LC polyphenol analysis demonstrated that the behavior of individual constituents has still to be enlightened.
Assuntos
Achyrocline/química , Flavonoides/química , Fenóis/química , Cromatografia Líquida , Cor , Dessecação , Estabilidade de Medicamentos , Flavonoides/efeitos da radiação , Temperatura Alta , Luz , Fenóis/efeitos da radiação , Fotoquímica , Polifenóis , Pós , Padrões de Referência , Olfato , Temperatura , Fatores de Tempo , Raios UltravioletaRESUMO
Foi realizada a análise térmica de esparfloxacino, fluorquinolona de terceira geração que possui potente atividade contra bactérias Gram-positivas, como Streptococcus pneumoniae e Staphylococcus aureus inclusive cepas meticilina resistentes (MRSA), bactérias Gram-negativas, anaeróbios, Legionella spp., Mycoplasma spp., Chlamydia spp. e Mycobacterium spp. Nas curvas DTA observa-se pico endotérmico de fusão na temperatura de 276,5ºC. A curva DTA, em ar sintético, apresenta dois picos exotérmicos (341,6 e 579,2ºC), atribuídos à decomposição do composto. A curva TG permite observar a perda de massa total em duas etapas, entre as temperaturas de 285,5 e 645,3ºC. A curva DTA, em atmosfera de nitrogênio, apresenta pico exotérmico de decomposição na temperatura de 340,0ºC e na curva TG, a perda de massa inicia-se na temperatura de 254,4º