Thermal Analysis Applied to Verapamil Hydrochloride Characterization in Pharmaceutical Formulations

Yoshida, María Irene; Gomes, Elionai Cassiana Lima; Soares, Cristina Duarte Vianna; Cunha, Alexandre Frinhani; Oliveira, Marcos Antônio de

doi:10.3390/molecules15042439

Cited by 43 publications

(30 citation statements)

References 23 publications

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“…Any change in the quality of a class II drug caused by stability problems directly influences the bioavailability of the drug (Yoshida et al, 2010(Yoshida et al, , 2011.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, intrinsic stability and kinetic studies are key components in the discovery of potential drug degradation products, even though these products may not occur under normal medication storage conditions (Yoshida et al, 2010(Yoshida et al, , 2011.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The t 90 is often interpreted as the shelf-life of a drug. This is calculated through an extrapolation of the Arrhenius equation, and the value determines the drug lifetime at 298 K (Cides et al, 2006;Yoshida et al, 2010Yoshida et al, , 2011.The following equations can be used to describe the observed kinetics of degradation in solution:Arrhenius equation (1): (1) where: k = rate constant, Ea = activation energy, A = pre- Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate 547 exponential factor, T = temperature in Kelvin, R = gas constant (8.314 J mol -1 K -1 ). The aim of this paper was to develop and optimize an analytical HPLC method for determination of fibrates and possible degradation products, to evaluate the intrinsic stability of these drugs under stress conditions, and to study the kinetics of degradation of these drugs that are so susceptible to chemical reactions.…”

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confidence: 99%

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Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

Oliveira

Silva

Campos

2016

Braz. J. Pharm. Sci.

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Fibrates are drugs used for the treatment of hypertriglyceridemia and for the prevention of atherosclerosis. Three drugs in the fibrate class, ciprofibrate, fenofibrate and bezafibrate, were chosen for this study because their raw materials are readily available and because scientific publications on these compounds is limited. To evaluate their intrinsic stability, the drugs were exposed to a test condition (temperature, oxidation, UV light exposure, hydrolysis at different pH values and metal ions in solution) and then were subjected to analysis by HPLC. The samples were run on a C18 column, with a flow rate of 1.0 mL min -1 in a mobile phase consisting of methanol: 0.01 % phosphoric acid v/v (80:20), with variable detection wavelengths in the UV spectra. The analysis methodology showed satisfactory performance parameters. The three drugs were very unstable, degrading in each of the conditions evaluated. The test conditions of acid and basic hydrolysis showed the most significant degradation. The results demonstrated that the drugs in this class are unstable. Based on these experimentally determined degradation kinetics, it is easy to understand and emphasize the importance of the lack of liquid dosage forms on the market for fibrates because of their instability.Uniterms: Hypertriglyceridemia/fibrates. Fibrates stability/study. Fibrates degradation products/High Perfomance Liquid Chromatography (HPLC). Fibrates/Degradation kinetics. INTRODUCTIONFibrates are drugs used for the treatment of hypertriglyceridemia and for the prevention of atherosclerosis, and are represented by the following compounds: clorfibrate, ciprofibrate, bezafibrate, fenofibrate and geozila. Fibrates decrease triglyceride levels and increase HDL-C levels, the latter effect is more pronounced in patients with hypertriglyceridemia. The effect on LDL-C levels varies. They may reduce LDL-C levels in patients with low triglycerides, but may paradoxically increase levels for patients with high triglyceride levels. Fibrates also significantly reduce the levels of highly atherogenic remnant lipoproteins, and are more efficient than statins in doing so (Schulz, 2006).Among the fibrates, three drugs were chosen for the execution of this project: ciprofibrate, fenofibrate and bezafibrate (Figure 1). The drugs were chosen based on the availability of raw materials and evidence of few scientific publications regarding the drugs on the subject of research.Some analytical methods have been developed for the analysis of ciprofibrate, fenofibrate and bezafibrate by HPLC/UV (Nascimento et al., 2011;Salama et al., 2011;Jain et al., 2012;Kumbhar et al., 2013;Wei et al., 2008). The vast majority of these analytical methodologies used reverse phase columns, mainly octadecyl silane, with a controlled acidic pH solution for the mobile phase and detection in the ultraviolet range.Few articles have been published on the stability of the chosen fibrates (Salama et al., 2011;Jain et al., 2012;Kumbhar et al., 2013), and none were found that identified degradation pro...

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“…Any change in the quality of a class II drug caused by stability problems directly influences the bioavailability of the drug (Yoshida et al, 2010(Yoshida et al, , 2011.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

Oliveira

Silva

Campos

2016

Braz. J. Pharm. Sci.

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“…Verapamil (VER), 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methyl-amino]-2-propan-2-yl-pentanenitrile, is a calcium channel-blocking drug and is an effective agent for the treatment of hypertension, supraventricular arrhythmias and angina pectoris (Shibukawa and Wainer, 1992;Lankford and Bai, 1995;Sawicki, 2001;Yoshida et al, 2010).…”

Section: Brazilian Journal Of Chemical Engineeringmentioning

confidence: 99%

Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

Cremasco

Santana²

2015

Braz. J. Chem. Eng.

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-Verapamil is a chiral drug that is marketed in its racemic form, but because of the pharmacological effects due to molecule's chirality, one of the enantiomers is more potent, and the other exhibits different activities of therapeutic interest. The preparative separation of the verapamil enantiomers was performed using a continuous Varicol unit operated on a scale of 1 g/day. Amylose tris(3,5-dimethylphenylcarbamate) functioned as the stationary phase, and n-hexane/isopropanol/ethanol mixtures were used as the mobile phase. Diethylamine was used as the additive. The enantiomeric purities were 93.0% for S-(-)-verapamil and 92.0% for R-(+)-verapamil in the raffinate and extract streams, respectively. The unit provided productivities of 0.18 kg of raffinate per day per kg of adsorbent and 0.20 kg of extract per day per kg of adsorbent when using a feed concentration of 12.5 g L -1 .

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pH‐sensitive polyelectrolyte films derived from submicron chitosan/Eudragit^® L 100‐55 complexes: Physicochemical characterization and in vitro drug release

Čalija

Savić

Krajišnik

et al. 2015

J of Applied Polymer Sci

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The objectives of this study were to prepare films from submicron chitosan/Eudragit V R L100-55 polyelectrolyte complexes (CH/EL PEC) and to assess the influence of CH molecular weight and CH/EL mass ratio on their structure and drug-release properties. The films were obtained by a simple, environmentally friendly, casting/solvent evaporation method and the verapamil hydrochloride (VH) was used as model drug. Submicron size, narrow size distribution, and acceptable stability of CH/EL PECs were confirmed by DLS and laser Doppler microelectrophoresis. SEM analysis revealed nonporous inner structure and flat surface of the films. Interactions between comprising polymers and formation of CH/EL PEC were established by DSC and FT-IR spectroscopy. In vitro swelling and drug release studies revealed the pH sensitivity of the films, with burst drug release in acidic conditions (pH 1.2) and sustained release in phosphate buffers pH 5.8, 6.8, and 7.4. The slowest VH release was achieved from the films prepared from equal amounts of EL and CH of higher molecular weight, confirming the significance of the CH/EL ratio and CH molecular weight on their ability to sustain drug release. The obtained results suggested that presented, simple, and eco-friendly preparation procedure can be used to obtain pH-sensitive CH/EL PEC films with a promising potential as drug carriers.

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Thermal Analysis Applied to Verapamil Hydrochloride Characterization in Pharmaceutical Formulations

Cited by 43 publications

References 23 publications

Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

pH‐sensitive polyelectrolyte films derived from submicron chitosan/Eudragit^® L 100‐55 complexes: Physicochemical characterization and in vitro drug release

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Thermal Analysis Applied to Verapamil Hydrochloride Characterization in Pharmaceutical Formulations

Cited by 43 publications

References 23 publications

Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

pH‐sensitive polyelectrolyte films derived from submicron chitosan/Eudragit® L 100‐55 complexes: Physicochemical characterization and in vitro drug release

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pH‐sensitive polyelectrolyte films derived from submicron chitosan/Eudragit^® L 100‐55 complexes: Physicochemical characterization and in vitro drug release