The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon
SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix ...composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon
SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon
SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil
1 w/w %, magnesium stearate 0.5 w/w % and Avicel
up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon
SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.
Amiodarone low solubility and high permeability is the limiting step for its bioavailability, therefore new formulations are needed to improve the solubility of amiodarone either to increase its oral ...bioavailability or to reduce its toxic effects. Complexation of amiodarone with cyclodextrin results in improved dissolution rate, solubility, and allows for a more controlled drug release. We characterized the acute toxicity of a new amiodarone 2-hydroxypropyl-β-cyclodextrin complex (AMD/HP-β-CD) as powdered form and as a matrix based on Kollidon® and chitosan, administered intraperitoneally in laboratory animals. There were developed two formulations of matrix: one containing only pure AMD as a control sample (Fc) and one containing the inclusion complex with the optimal solubility (F). AMD was equitoxic with HP-β-CD after intraperitoneal administration (289.4 mg/kg for AMD and 298.3 mg/kg for AMD/HP-β-CD), with corresponding histopathological changes. The matrix based formulations presented higher LD50 values for acute toxicity, of 347.5 mg/kg for Fc and 455.6 mg/kg for F10, conducting to the idea of a safer administration because KOL and CHT matrix modified the solubility and controlled the AMD release. The LD50 is 1.5 higher for AMD/HP-β-CD included in a KOL and CHT based matrix compared to the pure AMD, administered intraperitoneally.
In various drug delivery systems, solid lipid nanoparticles are dominantly lipid-based nanocarriers. Amiodarone hydrochloride is an antiarrhythmic agent used to treat severe rhythm disturbances. It ...has variable and hard-to-predict absorption in the gastrointestinal tract because of its low solubility and high permeability. The aims of this study were to improve its solubility by encapsulating amiodarone into solid lipid nanoparticles using two excipients—Compritol® 888 ATO (pellets) (C888) as a lipid matrix and Transcutol® (T) as a surfactant. Six types of amiodarone-loaded solid lipid nanoparticles (AMD-SLNs) were obtained using a hot homogenization technique followed by ultrasonication with varying sonication parameters. AMD-SLNs were characterized by their size distribution, polydispersity index, zeta potential, entrapment efficiency, and drug loading. Based on the initial evaluation of the entrapment efficiency, only three solid lipid nanoparticle formulations (P1, P3, and P5) were further tested. They were evaluated through scanning electron microscopy, Fourier-transform infrared spectrometry, near-infrared spectrometry, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The P5 formulation showed optimum pharmaco-technical properties, and it had the greatest potential to be used in oral pharmaceutical products for the controlled delivery of amiodarone.
The aim of this work was to obtain an inclusion complex between HP-β-CD and amiodarone in order to increase the solubility of this active agent. Drug–cyclodextrin interactions in solution were ...investigated using phase solubility studies. The Fourier transform infrared spectroscopy (FT-IR) spectra revealed the presence of the interactions between the components of the inclusion complex. Changes in crystallinity of the drug inside the inclusion complex were confirmed by X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). Thermogravimetric (TG) results demonstrated the modification of the drug thermal behavior due to the interactions with the host cyclodextrin. The dissolution rate of amiodarone from the inclusion complex was considerably increased as compared to dissolution of the pure drug. It has been established that the complexation of amiodarone with HP-β-CD offers the possibility to increase its aqueous solubility without the modification of its original structure.
The aim of this study was to improve the solubility of amiodarone hydrochloride (AMD) and the drug release using its inclusion complexes with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion ...complexes were prepared by coprecipitation and freeze-drying. The solubility enhancement of AMD/HP-β-CD inclusion complexes by 4–22 times was evaluated by the phase solubility method. The inclusion complexes were studied both in solution and in solid state by spectroscopic methods, dynamic light scattering (DLS) and zeta potential analysis, SEM, and DSC. The formulations of AMD/HP-β-CD inclusion complexes both as powdered form and as matrix tablets showed superior pharmacokinetic performance in improving loading and release properties in respect of those of the insoluble AMD drug. In vitro kinetic study reveals a complex mechanism of release occurring in three steps: the first one being attributed to a burst effect and the other two to different bonding existing in inclusion complexes. An in vivo test on matrix tablets containing Kollidon® and chitosan also reveals a multiple (at least two) peaks release diagram because of both structures of the inclusion complexes and also of different sites of absorption in biological media (digestive tract).
A NEW SPECTROPHOTOMETRIC METHOD FOR THE ASSAY OF LISINOPRIL Vieriu, Mădălina; Tântaru, Gladiola; Apostu, M ...
Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi,
10/2015, Letnik:
119, Številka:
4
Journal Article
Recenzirano
A new spectrophotometric method for the assay of lisinopril using 2,4-dinitrophenol as reagent is described.
The method involved the addition of 2,4-dinitrophenol to lisinopril in methanol followed ...by absorbance measurement at 400 nm. Experimental conditions that provide wide linear range, maximum sensitivity, selectivity, accuracy and precisions were optimized.
Beer's law was obeyed in the concentration range 2.0-14.0 μg/mL. Linear regression equation of calibration graph was A = 0.005 + 0.045 x concentration, with a regression coefficient (r) of 0.9995 (n = 8). The limits of detection (LOD) and quantification (LOQ) calculated according to the ICH guidelines were 0.42 and 1.42 μg/mL, respectively. Accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different lisinopril concentrations; the intra-day and inter-day RSD was < 1.43% and accuracy was better than 1.72%.
The proposed method is simple, easy to perform, sensitive, linear, precise, accurate and robust.
The formulation of sustained release tablets of AMD-HCl using KOLLIDON SR as matrix-forming agent. Chitosan, a natural polysaccharide with superior hydrating and absorbing properties was used in the ...formulation stage to optimize the release characteristics of those matrix tablets.
Nine formulations of sustained release matrix tablets of AMD x HCl (200 mg/tablet) were prepared through direct compression. The concentrations of matrix forming agents were included as independent variables of a type 2(3) mixed factorial plan in order to develop formulations of AMD-HCl with optimal release characteristics. The dependent variables of that plan were the amount of AMD released from the tablets studied by using in vitro dissolution testing. The test was carried out in the paddle apparatus II for 12 hours in two pH media that were relevant to oral delivery: 2 hours at pH 1.2 and 10 hours at pH 6.8. The released AMD-HCl was quantitatively determined through a validated HPLC method.
The increase in KOL concentration leads to a decrease in AMD release rate at both pH values. The use of CHT resulted in a decrease of AMD release only at pH 6.8 in formulations with the lowest concentration of KOL.
The retarding effect on the release of AMD-HCl in the tablets developed in this study was directly proportional to the KOL concentration in the formulation.
Bisoprolol fumarate is prescribed for the treatment of hypertension and angina pectoris.
The purpose of this study was to develop a simple, sensitive, accurate, and reproducible method for estimation ...of bisoprolol fumarate in tablets.
The proposed method was based on a yellow colored complex formed with tropaeolin 00, extractable in dichloromethane with maximum absorbance at 412 nm. The method was validated statistically.
The linearity domain was observed in the concentration of 5-30 microg/ml. The recovery studies confirmed the accuracy of the proposed method.
The proposed method can be applied for the routine analysis of bisoprolol from formulations.
Visible spectrophotometric method for amiodarone Bosînceanu, Andreea; Popa, Graţiela; Tântaru, Gladiola ...
Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi,
2012 Jan-Mar, Letnik:
116, Številka:
1
Journal Article
Recenzirano
Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmia, both ventricular and supraventricular (atrial) arrhythmia. A spectrophotometric method for the assay of amiodarone was ...established. Based on the reduction of potassium ferricyanide in hydrochloric acid medium to potassium ferrocyanide forming a blue colored complex ferric ferrocyanide with Fe (III) ions. The compound was most stable in a mixture of ethylic alcohol and water (2:1, v/v) and it had an absorption maximum at 725 nm. The data were according to the Lambert-Beer Law in the concentration range of 0.5-5.0 microg/sample: correlation and coefficient R = 0.99977, R2 = 0.999541, slope of the line 0.12775, intercept 0.042077. The detection limit (DL) was 0.1032 microg/sample and the quantification limit (QL) 0.344 microg/ sample.
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