Binary Mixtures of Meloxicam and L-Tartaric Acid for Oral Bioavailability Modulation of Pharmaceutical Dosage Forms.

Binary mixtures of active pharmaceutical ingredients (API) are researched to improve the oral bioavailability of pharmaceutical dosage forms. The purpose of this study was to obtain mixtures of meloxicam and L-tartaric acid because tartaric acid improves intestinal absorption and meloxicam is more soluble in a weakly basic environment. The mixtures in the 0-1 molar fraction range, obtained from solvent-assisted mechanosynthesis, were investigated by differential scanning calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, Fourier Transform Raman spectroscopy (FT-Raman), X-ray powder diffraction (XRD) and solubility tests. The physicochemical characteristics of the compounds obtained from DSC data reveal, for the first time, the formation of a co-crystal at meloxicam molar fraction of 0.5. FTIR spectroscopy data show the existence of hydrogen bonds between the co-crystal components meloxicam and L-tartaric acid. FT-Raman spectroscopy was used complementary with FT-IR spectroscopy to analyze the pure APIs and their mixtures, to emphasize the appearance/disappearance and the shifts of the position/intensity of vibrational bands, following the formation of hydrogen-bonded structures or van der Waals interactions, and to especially monitor the crystal lattice vibrations below 400 cm-1. The experimental results obtained by X-ray powder diffraction confirmed the formation of the co-crystal by the loss and, respectively, the apparition of peaks from the single components in the co-crystal diffractogram. The solubility tests showed that the co-crystal product has a lower aqueous solubility due to the acidic character of the other component, tartaric acid. However, when the solubility tests were performed in buffer solution of pH 7.4, the solubility of meloxicam from the co-crystal mixture was increased by 57% compared to that of pure meloxicam. In conclusion, the studied API mixtures may be considered potential biomaterials for improved drug release molecular solids.

Water-Soluble Starch-Based Copolymers Synthesized by Electron Beam Irradiation: Physicochemical and Functional Characterization.

Modification of natural polymers for applications in the treatment of waste and surface waters is a continuous concern of researchers and technologists in close relation to the advantages they provide as related to classical polymeric flocculants. In this work, copolymers of starch-graft-polyacrylamide (St-g-PAM) were synthesized by electron beam irradiation used as the free radical initiator by applying different irradiation doses and dose rates. St-g-PAM loaded with ex situ prepared silver nanoparticles was also synthesized by using an accelerated electron beam. The graft copolymers were characterized by chemical analysis, rheology, and differential scanning calorimetry (DSC). The results showed that the level of grafting (monomer conversion coefficient and residual monomer concentration), intrinsic viscosity and thermal behavior (thermodynamic parameters) were influenced by the irradiation dose, dose rate and presence of silver nanoparticles. The flocculation performances of the synthesized copolymers were also tested on water from the meat industry in experiments at the laboratory level. In the coagulation-flocculation process, the copolymer aqueous solutions showed good efficiency to improve different water quality indicators.

Compatibility of Drotaverine Hydrochloride with Ibuprofen and Ketoprofen Nonsteroidal Anti-Inflammatory Drugs Mixtures.

Formulations with two or more active pharmaceutical ingredients (APIs) are a researched trend due to their convenient use compared with multiple medications. Moreover, drug-drug combinations may have a synergistic effect. Drotaverine hydrochloride (D-HCl) is commonly used for its antispasmodic action. The combination of a spasmolytic and an analgesic drug such as ibuprofen (Ibu) or ketoprofen (Ket) could become the answer for the treatment of localized pain. D-HCl:Ibu and D-HCl:Ket drug-drug interactions leading to the formation of eutectic compositions with increased bioavailability, obtained by mechanosynthesis, a green, solvent-free method was explored for the first time. The compatibility of Ibuprofen, Ketoprofen, and Drotaverine Hydrochloride was investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-Transform Infrared spectroscopy (FTIR). Solid-liquid equilibrium (SLE) phase diagrams for the binary systems of active pharmaceutical ingredients were developed and the Tammann diagrams were designed to determine the eutectic compositions. The excess thermodynamic functions GE for the pre-, post-, and eutectic compositions were obtained using the computed activity coefficients data. Results show that drotaverine-based pharmaceutical forms for pain treatment may be obtained at 0.9 respectively 0.8 molar fractions of ibuprofen and ketoprofen which is advantageous because the maximum allowed daily dose of Ibu is about 6 times higher than those of D-HCl and Ket. The obtained eutectics may be a viable option for the treatment of pain associated with cancer therapy.

Thermal Behavior of the Nimesulide-Salicylic Acid Eutectic Mixtures Prepared by Mechanosynthesis and Recrystallization.

Nimesulide, salicylic acid and their binary mixtures were studied by differential scanning calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The study of such systems is a promising and viable approach for solving the problem of poor solubility of materials in general and drug systems in particular. All areas of human activity are inextricably linked to materials, and thus, the study presented in the paper and not reported in the literature is very important and provides useful data for those working in various fields. The eutectic mixtures were obtained by mechanosynthesis and by recrystallization from ethanol over the entire 0-1 range of molar fractions. For both situations at the molar fraction of nimesulide 0.5, the mixture has a eutectic that suggests an increase in solubility at this composition. The interactions that take place between the components were determined with the help of the excess thermodynamic functions (GE, SE, µE), which highlight the deviation from the ideality of the considered binary systems.

Thermodynamic study of binary system Propafenone Hydrocloride with Metoprolol Tartrate: solid-liquid equilibrium and compatibility with α-lactose monohydrate and corn starch.

Solid-liquid equilibrium (SLE) for binary mixture of Propafenone Hydrocloride (PP) with Metoprolol Tartrate (MT) was investigated using differential scanning calorimetry (DSC) and corresponding activity coefficients were calculated. Simple eutectic behavior for this system was observed. The excess thermodynamic functions: G(E) and S(E) for the pre-, post-, and eutectic composition have been obtained using the computed activity coefficients data of the eutectic phase with their excess chemical potentials µi(E) (i=1, 2). The experimental solid-liquid phase temperatures were compared with predictions obtained from available eutectic equilibrium models. The results indicate non-ideality in this mixture. Also, the compatibility of each component and their eutectic mixture with usual excipients was investigated, and the DSC experiments indicate possible weak interactions with α-lactose monohydrate and compatibility with corn starch. The results obtained were confirmed by FT-IR measurements.

HPLC separation of acetaminophen and its impurities using a mixed-mode reversed-phase/cation exchange stationary phase.

Determination of acetaminophen and its main impurities: 4-nitrophenol, 4'-chloroacetanilide, as well as 4-aminophenol and its degradation products, p-benzoquinone and hydroquinone has been developed and validated by a new high-performance liquid chromatography method. Chromatographic separation has been obtained on a Hypersil Duet C18/SCX column, using gradient elution, with a mixture of phosphate buffer (pH = 4.88) and methanol as a mobile phase. Analysis time did not exceed 14.5 min and good resolutions, peak shapes and asymmetries have resulted. The linearity of the method has been tested in the range of 5.0-60 µg/mL for acetaminophen and 0.5-6 µg/mL for the other compounds. The limits of detection and quantification have been also established to be lower than 0.1 µg/mL and 0.5 µg/mL, respectively. The method has been successfully applied for the analysis of commercial acetaminophen preparations.

Inclusion complexes of cyclodextrins with biradicals linked by a polyether chain--an EPR study.

Complexation of beta-cyclodextrin with flexible nitroxide biradicals linked by a polyethylene glycol chain was monitored by EPR spectroscopy. The EPR spectra of the uncomplexed biradicals show an exchange interaction due to the flexibility of the polyethylene glycol chain. Complexation with cyclodextrin leads to the disappearance of the exchange interaction in the EPR spectra. The complexation can be reversed by the addition of competing guests (e.g., adamantane derivatives). At high concentration, the inclusion complexes precipitate, and differential scanning calorimetry (DSC) of the precipitates proved the formation of complexes. Elemental analysis data revealed that the complexes contain several cyclodextrin units per biradical but that the composition was not stoichiometric.