ABSTRACT
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.
Subject(s)
Antiparkinson Agents/administration & dosage , Levodopa/administration & dosage , Administration, Inhalation , Antiparkinson Agents/chemistry , Antiparkinson Agents/radiation effects , Chromatography, High Pressure Liquid , Drug Stability , Excipients , Kinetics , Levodopa/chemistry , Levodopa/radiation effects , Light , Limit of Detection , Nanoparticles , Pharmaceutical Solutions , Photochemistry , Reference Standards , Reproducibility of Results , Spectrophotometry, UltravioletABSTRACT
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.
Subject(s)
Antidepressive Agents, Second-Generation/analysis , Antidepressive Agents, Second-Generation/toxicity , Mianserin/analysis , Mianserin/toxicity , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Drug Stability , Hot Temperature , Humans , Hydrogen-Ion Concentration , Hydrolysis , In Vitro Techniques , Indicators and Reagents , Kinetics , Methanol , Monocytes/drug effects , Photolysis , Reproducibility of Results , Solvents , Tablets , Temperature , Ultraviolet RaysABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/chemistry , Chromatography, High Pressure Liquid/methods , Ketolides/chemistry , KineticsABSTRACT
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.
