Mixture Of Paracetamol Research Articles

The properties of chitosan and paracetamol in acidic water mixture by viscosity study for pharmaceutical and biomedical applications

ABSTRACT Paracetamol (PC), the active ingredient in Efferalgan, is an effervescent tablet medicine used in the treatment of mild-to-moderate pain. Chitosan (CH) is a biopolymer having immense structural possibilities for chemical and mechanical modifications to generate novel properties, functions and applications, especially in the pharmaceutical area. The dynamic viscosities, η, have been measured, and investigated for the mixture of CH in acidic water and paracetamol aqueous solutions over the entire range of the temperature 20–65°C, and concentrations of 1–10 g/l. The main objective of our research described here was to determine the viscometric properties of biopolymer solutions of CH in PC, as a function of the volume fraction fCH in the CH and PC mixture and temperatures. We identified three main concentration regimes, corresponding to a dilute regime, a critical regime and the semi-dilute regime. Our results showed that the CH/PC is a promising mixture for use in pharmaceutical and antibacterial applications. The chitosan shows antimicrobial activity against various microorganisms, including bacteria.

Novel analytical method based on chemometric models applied to UV–Vis spectrophotometric data for simultaneous determination of Etoricoxib and Paracetamol in presence of Paracetamol impurities

The multivariate models that are used for spectral data analysis have many beneficial applications, and one of the important applications is the analysis of drugs and their impurities. Three Chemometrically-assisted spectrophotometric models have been proposed and validated. The proposed models are Partial Least Squares (PLS), Artificial Neural Networks (ANN), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). The advanced chemometric models were applied to resolve the significantly overlapping spectra of Etoricoxib (ETO) and Paracetamol (PCM), along with impurities of PCM namely; P-aminophenol (PAP) and P-hydroxy acetophenone (PHA). The proposed models succeeded in simultaneously analyzing the mixture of ETO and PCM along with the impurities of PCM. So, the proposed techniques can be used without requiring a separation step in the analysis of pharmaceutical formulation. Moreover, no significant differences were found when the results of the suggested and published chemometric models were compared statistically with the reported HPLC method.

BAYESIAN REGRESSION OF OVERLAPPING IBUPROFENPARACETAMOL UV SPECTRA

Bayesian regression has been successfully applied to predict a full spectrum of ibuprofen and paracetamol binary mixture. The Bayesian regression models were constructed using 25 ibuprofen and paracetamol mixture with concentration combinations of 6, 8, 10, 12, and 14 ppm for each ibuprofen and paracetamol. The models were validated using synthetic test solutions to acquire the model’s accuracy and precision. The intercept, slopes, and model mean squared error indicated that paracetamol prediction on the test and sample solution was more reliable than ibuprofen. The recovery ranges and mean squared error for both the test solution and pain relief tablet confirm that the models have good accuracy in predicting ibuprofen and paracetamol binary mixture in the pharmaceutical drug. The measurement was carried out at wavelengths ranging from 220 to 270 nm.

Physical and acoustical properties of paracetamol in binary mixtures of water + propylene glycol

Experimental results of physical properties (density, viscosity and refractive index) and acoustical property (speed of sound) for a range of concentrations of pharmaceutical drug paracetamol (PCM) in the binary mixtures of distilled water (DW) + propylene glycol (PG) are reported at a constant temperature of 310.15 K. Determined values of these properties are analyzed to gain information about the interaction between PCM and binary mixtures of DW + PG as well as to understand structural changes in the prepared solutions. Thermodynamic properties such as specific volume and specific gravity are also evaluated using the experimental values of density for all solutions. Results showed their applicability in the field of pharmaceutical sciences at various stages of drug formulation designing, dosage selection, etc.

Design strategy and preparation of a conductive layered electrochemical sensor for simultaneous determination of ascorbic acid, dobutamine, acetaminophen and amlodipine

Cardiovascular disease is a class of diseases that involves the heart or blood vessels. It includes coronary artery diseases such as angina and myocardial infarction. In addition, hypertension is quantitatively the most important risk factor for premature cardiovascular disease. Dobutamine (DB) and amlodipine (AM) are medications commonly used for treating these diseases. Therefore, simultaneous determination of these drugs in presence of interfering compounds in biological fluids; paracetamol (PA), and ascorbic acid (AA) is essential for patients under medical treatment by these drugs. An innovative strategy is introduced for fabrication of a novel layered composite based on layer-by-layer modification of a glassy carbon electrode surface (GC) with multi-walled carbon nanotubes (CNT), ionic liquid crystal (ILC), graphene (RGO) and 18-Crown-6 (CW); (GC/CNT/ILC/RGO/CW). The layered sensor exhibited excellent electro-catalytic activity for determination of AA in the drugs mixture and simultaneous determination of DB, PA, and AM in human serum in linear dynamic ranges; 0.4 → 40 μM, 0.02 → 40 μM, 0.001 → 20 μM and 0.008 → 30 μM with low detection limit values; 9.24 nM, 0.497 nM, 0.0906 nM and 0.139 nM, respectively and low quantification limit values; 30.8 nM, 1.66 nM, 0.302 nM and 0.463 nM, respectively. Further practical application was performed for quantitative analysis of AA, DB, PA and AM in their pharmaceutical formulations.

Interactions Between Paracetamol and Hypromellose in the Solid State.

Hydroxypropyl methylcellulose (hypromellose) is a widely known excipient commonly used in the preparation of drug formulations. It can interact with some active pharmaceutical ingredients (APIs), thereby contributing to a reduction in crystallinity, serve as a solvent for API or form stable dispersion with no tendency to aggregation. The aim of the present study was to investigate the effect of hypromellose on the solubility, miscibility and amorphization of paracetamol in mixture with this polymer. Homogenized mixtures of paracetamol with hypromellose were studied using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier transform infrared (FT-IR) and Raman methods to obtain a deeper insight into the interactions between ingredients in solid state including phase diagram construction for crystalline API and amorphous polymer. A DSC study revealed potential interaction between ingredients resulting in reduced paracetamol crystallinity. This was proved using heating-cooling-heating test to confirm paracetamol amorphization. FT-IR and Raman investigations excluded chemical reaction and hydrogen bonding between ingredients. The phase diagram developed facilitates predictions on the solubility of API in polymer, on the mutual miscibility of ingredients and on the temperature of mixture glass transition.

Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance

Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90–97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and Cmax. A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and Cmax of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.

The employment of UV-spectroscopy combined with multivariate calibration for analysis of paracetamol, Propyphenazone and caffeine

The reference method for simultaneous analysis of drugs is chromatography, however, this technique is expensive, complex, and needs excessive sample preparation; therefore, some simple methods like UV spectroscopy is proposed. Assisted with multivariate calibration, it is possible to analyze drugs using UV spectroscopy without prior separation. This study is intended to use UV spectroscopy coupled with multivariate calibration of partial least square (PLS) for simultaneous analysis of paracetamol (PCT), propyphenazone (PROPI), and caffeine (CAFF) in tablet dosage form. The calibration model is prepared by developing a series 20 mixture of PCT, PROPI and CAFF with certain composition randomly and its absorbance is measured at wavelength of 220-313 nm with an interval of 3 nm. The performance of calibration model was assessed by coefficient of determination (R 2 ), root mean square error of calibration (RMSEC) and root mean square error of cross validation (RMSECV). The R 2 values for the correlation between actual values of PCT, PROPI and CAFF and predicted values using UV-spectroscopy combined with PLS are 0.9994; 0.9878; and 0.9919, respectively. The calibration errors expressed with RMSEC are 0.027%, 0.082% and 0.043% for PCT, PROPI and CAFF, respectively. While, during cross validation using “leave one out” technique, RMSECV values obtained are 0.062%, 0.095% and 0.982%, respectively for PCT, PROPI and CAFF. The level of drugs obtained are 226.76 ± 14.49 mg/tablet (equivalent to 90.70% from labeled claim) for PCT, 135.74 ± 11.23 mg/tablet (equivalent to 90.49% from labeled claim) for PROPI and 51.69 ± 2.35 mg/tablet (equivalent to 103.38% from labeled claim) for CAFF.

The flow properties and presence of crystals in drug-polymer mixtures: Rheological investigation combined with light microscopy

The presence of solid matter in polymer melts affects the rheological properties of a drug-polymer mixture, and thus the processability of these mixtures in melt-based processes. The particle morphological changes related to dissolution and crystal growth in the mixtures of paracetamol and ibuprofen with polyethylene oxide and methacrylate copolymer (Eudragit® E PO) were observed by polarized microscopy simultaneously while measuring their rheological properties within temperature ranges relevant for melt processes, such as hot melt extrusion and fused deposition modeling 3D printing. The dissolution of solid crystalline matter into the molten polymer and its effects on the rheological parameters showed that the plasticization effect of the drug was highly dependent on the temperature range, and at a temperature high enough, plasticization induced by the small-molecule drugs could enhance the flowability even at very high drug loads. Therefore, even supersaturated mixtures can be plasticized efficiently, enabling their melt processing, such as hot melt extrusion or 3D printing. The combination of rheometry and polarized light microscopy proved to be very useful for studying the link between morphological changes in the drug-polymer and the flow behavior of the drug-polymer mixtures at different temperature ranges and deformation modes.

A simple synthesis of nitrogen doped porous graphitic carbon: Electrochemical determination of paracetamol in presence of ascorbic acid and p-aminophenol

Graphite paste electrode modified with nitrogen doped porous carbon (NDPC) is used for the detections of paracetamol (PCM), ascorbic acid (AA) and p-aminophenol (PAP) at relatively low concentration. NDPC is synthesized by direct carbonization of Zn(OAc)2 incorporated melamine-formaldehyde resin microsphere. The NDPC shows small pore diameters centered at 3.14 nm and 8.12 nm and has a pseudo graphitic structure with reasonable porous matrix. The lower limit of detections (S/N = 3) for PCM, AA, and PAP are found to be 30 nM, 720 nM and 10 nM respectively. Under optimized experimental condition, the linear ranges of determination for PCM and AA are 1–400 μM, 10–2700 μM respectively in mixture. Similarly for PCM and PAP mixture, the linear ranges of determination are found to be 1–90 μM. It is also used for the analysis of urine and pharmaceutical products with better sensitivity.

Compaction of functionalized calcium carbonate, a porous and crystalline microparticulate material with a lamellar surface

In the present study, we aimed to characterize the compressibility and compactibility of the novel pharmaceutical excipient, functionalized calcium carbonate (FCC). We studied three FCC modifications and compared the values for compressibility and compactibility with mannitol, microcrystalline cellulose (MCC), and ground calcium carbonate (CC 330) as well as mixtures of paracetamol and MCC or FCC at drug loads of 0%, 25%, 50%, 75%, and 100% (w/w). We used Heckel analysis, modified Heckel analysis, and Leuenberger analysis to characterize the compaction and compression behavior of the mixtures. Compaction analysis of FCC showed this material to markedly differ from ground calcium carbonate, exhibiting properties, i.e. plastic deformability, similar to those of MCC. This effect was attributed to the highly lamellar structure of FCC particles whose thickness is of the order of a single crystal unit cell. According to Leuenberger parameters, we concluded that FCC-based tablet formulations had mechanical properties equal or superior to those formulated with MCC. FCC tablets with high tensile strength were obtained already at low compressive pressures. Owing to these favorable properties (i.e. marked tensile strength and porosity), FCC promises to be suitable for the preparation of solid dosage forms.

Studying the compatibility of a metoclopramide-HCl–paracetamol mixture via IHCMC and establishing a validated RP-HPLC method for its determination in tablets

Currently metoclopramide hydrochloride (MCP-HCl) and paracetamol (PCM) are co-formulated together in a tablet form, which is widely used in relief of painful migraine. The purpose of this work was to investigate the physicochemical compatibility of this co-mixture in the solid form and in different media as well. A highly selective and sensitive RP-HPLC method was established to quantify MCP-HCl and PCM in the presence of their degradation products. Chromatographic separation was achieved on a C-8 column using phosphate buffer, acetonitrile and methanol (40 : 15 : 10, v/v/v, pH 3) as a mobile phase at a flow rate of 0.5 mL min−1 with UV detection at 220 nm. Isothermal Heat-Conduction Micro-Calorimetry (IHCMC) was used to investigate heat-flow caused by physico-chemical incompatibility. The method was linear within concentration ranges such as 20–80 μg mL−1 and 10–70 μg mL−1 for MCP-HCl and PCM, respectively. The LOD and LOQ of the method for determination of MCP-HCl and PCM were 0.501, 0.101, 1.67 and 3.39, respectively. Other analytical validation parameters such as accuracy, precision, selectivity and applicability of the method were evaluated using an external standard addition technique. The tablets containing MCP-HCl and PCM in the concentration ratio of 1 : 100 were analyzed by the method successfully via two concentration levels. Thermal analysis of solid mixtures of the drugs showed compatibility over short and long terms in contrast with their aqueous mixtures. So it is not recommended that this drug mixture be formulated in a liquid form.

Effect of Metoclopramide on the Excretion Rate of Paracetamol Using HPLC-DAD

A simple, precise, accurate and robust high-performance liquid chromatography assay was developed and validated for the simultaneous analysis of metoclopramide and paracetamol in human urine. The drugs were isolated from urine samples by solid-phase extraction using C8 cartridges, then analyzed on a C18 reversed-phase column using a mixture of aqueous phase (water containing 0.2% TEA adjusted to pH 3 using ortho-phosphoric acid) and methanol in a ratio of 80:20 (v/v). The method was found to be linear for both drugs in a concentration range of 0.5 to 160 µg/mL using a concentration of 10 µg/mL of internal standard (theophylline) in urine samples (r > 0.999). The accuracy of the method was higher than 91.73% (percentage of the grand mean of recoveries) and the precision was lower than 3.4% (overall percentage of relative standard deviation) for both metoclopramide and paracetamol. The method was applied to the determination of the drugs in urine samples obtained from male volunteers, following the administration of two formulations, one containing paracetamol alone (Paracetamol(®)) and the other containing a mixture of paracetamol and metoclopramide (Migracicid(®)). Determination of the drugs was conducted and the effect of increasing the rate of absorption, consequently increasing the mean urinary excretion of paracetamol due to the presence of metoclopramide in the pharmaceutical formulation, was recorded.

Simultaneous Determination of Paracetamol ,Chlorpheniramine Maleate and Ascorbic Acid in Tablet Dosage Form by HPLC

The mixture of paracetamol, chlorpheniramine maleate and ascorbic acid is widely used in medicine as anti flu remedy .Pharmaceutically ,this mixture isprepared as a tablet by different manufacturers and it has good reputation in the market .However, this drug mixture is still non-official in pharmacopoiea, butthe USP has described a non specific method of HPLC for the mixture of paracetamol with antihistamine and other antitussive drugs .&#x0D; Application of the USP- HPLC method was found unreliable for the analysis of tablet containing this drug mixture of three components, since different chromatographic conditions should be applied for each component. Some workers also prescribed a method of analysis by specific procedure for each component individually after previous extraction, which rather long and tedious.In this work; an HPLC method was developed by using the reversed phase mode of chromatography (ODS column) and a mobile phase consists of ammonium phosphate 0.1M and methanol 20% .the peaks of three components of the studied mixture were well separated and the retention times of ascorbic acid ,chlorpheniramine maleate and paracetamol were 2.10,2.76 and 6.60 Minutes respectively and the whole analysis was accomplished in 10 minutes.The accuracy and precision of this method were approved for the quantitative analysis of each component of the mixture.

SIMULTANEOUS DETERMINATION OF PARACETAMOL, PSEUDOEPHEDRINE HYDROCHLORIDE, AND DEXTROMETHORPHAN HYDROBROMIDE IN TABLETS USING MULTIVARIATE CALIBRATION METHODS COUPLED WITH HPLC-DAD

A new method using high performance liguid chromatography (HPLC) with diode array detection (DAD) was developed and validated for the simultaneous determination of paracetamol (PAR), pseudoephedrine hydrochloride (PSE), and dextromethorphan hydrobromide (DEX) in tablets. The spectrochromatograms of these compounds give the severely overlapping spectrochromatogram. This makes the use of univariate calibration impossible. Therefore, PLS and PCR were used to analyze the three-way data recorded by HPLC-DAD. These multivariate calibration methods were tested by analyzing the synthetic mixtures of PAR, PSE, and DEX. The recoveries were in the range of 96.1–100.2% and 97.1–100.4%, relative error of prediction (REP%) in the range of 0.5–6.7 and 0.8–7.0% were obtained for PLS and PCR, respectively. These methods were also applied to real samples containing the three drugs, and recoveries in the range of 99.0–106.0% and 99.6–106.3% were obtained for PLS and PCR, respectively. The results obtained by PLS and PCR statistically compared with the results obtained by the classical HPLC method. It was found that there were no significant differences between the means and the standard deviations of the results obtained by the multivariate calibration methods and classical method. HPLC-multivariate calibration methods have several advantages over the classical HPLC method. These advantages are the use of a simple mobile phase and shorter analysis time. Also, these methods do not require the internal standard and the gradient elution.

Multiple compression and plasto-elastic behaviour of paracetamol and microcrystalline cellulose mixtures.

Radial tensile strength, friability, ER/PC (elastic recovery/plastic compression) ratio and energy ratio analyses were evaluated for various mixtures of paracetamol and microcrystalline cellulose (Avicel). A good correlation occurred between the energy ratio and the other variables. Linear relationships were found between log tensile strength and percentage energy ratio and also between radial tensile strength and stress relaxation energy. Capping occurred when the percentage energy ratio was greater than 15% and the ER/PC ratio greater than 1.5. To produce tablets with acceptable tensile strength and friability, the percentage energy ratio for Avicel/paracetamol should be greater than 10%. The optimal mixture of the two powders, as far as the tensile strength, friability and absence of capping were concerned, was found to be 50% w/w Avicel, 50% w/w paracetamol.

Effects of solid-state reaction between paracetamol and cloperastine hydrochloride on the pharmaceutical properties of their preparations

Tablets containing both paracetamol (PM) and cloperastine hydrochloride (CLH) in a combination formulation prepared by standard vertical granulation technology were found to have altered pharmaceutical properties. The hardness and disintegration time of tablets containing both PM and CLH gradually increased during storage, and the cross-screw did not operate smoothly during preparation of the mixed powder. The objective of the present study was to investigate the mechanism of formation of eutectic mixtures consisting of PM and CLH. Binary mixtures of PM and CLH in various proportions were prepared as physical mixtures and analyzed by DSC to study their thermal behavior. Phase diagrams obtained from the endothermic peaks due to melting of physical mixtures of PM and CLH demonstrated the formation of eutectic mixtures with eutectic temperatures of 86.9–110.2°C depending on the ratio of constituents. The formation of the eutectic mixture was studied for a 50:50mol.% ratio of PM and CLH. PXRD analysis revealed that the eutectic mixture of PM and CLH is structurally different from native PM and CLH. The most probable interaction sites between PM and CLH were demonstrated by DSC analysis of a binary mixture of PM and CLH prepared by melt quenching.

Crystal growth rates of paracetamol in mixtures of water + acetone + toluene

AbstractCrystal growth rates of paracetamol (4‐hydroxyacetanilide) have been determined by seeded isothermal desupersaturation experiments at 16 °C in 23 different solvent mixtures of water + acetone + toluene. Parameters of different growth rate equations have been estimated by direct nonlinear optimization. At equal thermodynamic driving force, the growth rate depends on the composition of the solvent mixture. In the surface diffusion spiral growth model, this dependency can be described in terms of the interfacial energy between the solid and the solution. A reasonable prediction of the influence of the solvent composition on this interfacial energy is obtained if a proper estimation of the enthalpy of dissolution is done. For the case of paracetamol crystals growing in water + acetone + toluene mixtures this estimation needs to include an estimation of the entropy of fusion at the temperature of growth as well as of the nonideal entropy of mixing. © 2005 American Institute of Chemical Engineers AIChE J, 2005

Developmental effects of propyphenazone in analgesic and antipyretic combination with caffeine or paracetamol.

The aim of the study was to determine the influence of an over-the-counter (OTC) mixture of propyphenazone with caffeine or paracetamol on prenatal development. Propyphenazone:caffeine and propyphenazone:paracetamol mixtures were prepared with constant 3:1 and 3:5 ratios, respectively. Three dose levels of each of the mixtures were administered separately in Tween-80 water suspension once a day to pregnant Wistar rats on gestation days 8-14. The low dose was similar to the OTC preparations, 2.1 mg/kg of propyphenazone, 0.7 mg/kg of caffeine or 3.5 mg/kg of paracetamol. The middle dose was 21.0, 7.0 or 35.0 mg/kg, and the highest 210.0, 70.0 or 350.0 mg/kg for propyphenazone, caffeine or paracetamol, respectively. On day 21 of gestation the fetuses were delivered by hysterectomy. Dead or live fetuses, resorptions and the number of implantation sites were counted. Live fetuses were examined for external, visceral and skeletal malformation. Postimplantation mortality was calculated. Dose-dependent effects in the middle and high dose groups on fetal body weight/length and placental weight were found. No increase in external or internal congenital anomalies was found in any of the mixture-exposed groups. Prenatal coadministration of propyphenazone with caffeine or paracetamol caused intrauterine growth retardation but did not increase external or internal congenital anomalies. The risk of midline defects (umbilical hernia and gastroschisis) is discussed.

Experimental and modelistic approach to explain granulate inhomogeneity through preferential growth

Wet granulation of a powder mixture often leads to accumulation of the smallest particles in the large granules. The preferential uptake of these particles results in an inhomogeneous granulate. The aim of this study was to investigate the mechanism of preferential growth. For that purpose the growth of one single granule was followed by adding a droplet of binder liquid to a rotating powder mixture of paracetamol and lactose. The particle sizes of both components were varied. At various time points mass and paracetamol content of the granule was determined. The results showed in all cases that the fine particles have a relatively higher presence in the granule than the coarse particles. These observations were independent of the fact whether the fine particles consists of lactose or paracetamol. During layering growth of the granule, caused by radial penetration of the liquid, fine particles appear to have a higher affinity for growth than coarse particles. It was argued that small particles penetrate the pores of the granule more easily than large particles, leading to the preferential absorption of the fine constituents. A model based on this growth mechanism, was able to predict the experimental results. It was concluded that this non-random growth process underlies the formation of inhomogeneous granules.