V. A. Popkov

Furacilin Release from Solid Dispersions

The effects of solid dispersions (SDs) on furacilin solubility were studied. Furacilin and its SDs with polyethyleneglycol-1500 (PEG) and polyvinylpyrrolidone-10000 (PVP) were investigated. SD formation doubled furacilin solubility and increased its dissolution rate as the SD with PVP by 12 times compared with furacilin powder. It was supposed that several factors were responsible for the improved release of furacilin from the SD. These included reduced crystallinity, amorphization, and intermolecular interactions, presumably H-bonds.

Increases in the solubility of Mezapam by forming solid dispersions

The effects of solid dispersions (SD) on the solubility of Mezapam were investigated. Mezapam and its SD with polyethylene glycol 1500, polyvinylpyrrolidone 10,000, and β-cyclodextrin were studied. These SD increased the solubility and rate of dissolution of Mezapam. The solubility of Mezapam from SD increased by factors of 2 – 8. The rate of dissolution of Mezapam form SD increased by factors of 2 – 4. Use of a set of physicochemical study methods suggested that the improvements in the release of Mezapam from SD occurred as a result of decreases in crystallinity and increases in the formation of intermolecular complexes.

Solubility of erythromycin from solid dispersions

The effect of solid dispersion (SD) formation on the solubility of the antibiotic erythromycin has been studied using the parent substance of erythromycin and its SDs with polyethyleneglycol (PEG-1500), polyvinylpyrrolidone (PVP-10000), and β-cyclodextrin. It is established that SD formation increases the solubility of the antibiotic by a factor of 1.3 – 1.8; the dissolution rate, 1.5 – 2.0. Results using a complex of physical and chemical methods suggest that the increase in erythromycin release from SDs takes place due to a decrease in the degree of crystallinity and the formation of intermolecular complexes.

Combination of two chromatographic methods in the study of the chemical composition of officinal herbs

Two complementary chromatographic methods, ion exclusion chromatography and gas-liquid chromatography, are suggested for the analysis of the chemical composition and the standardization of raw herbs. The potentialities and limitations of these methods are illustrated by the example of common valerian (Valeriana officinalis) and yarrow (Achillea millefolium). The chromatographic conditions required for the determination of ascorbic acid by the ion exclusion chromatography are determined.

The composition of the plants’ extracts included in the herbal mixtures used to treat the parodontal disease

The methods of gas-liquid chromatography and mass-selective detection were used to determine the composition of the volatile fraction of plant extracts included in herb mixtures used for treating parodontal disease. The following marker substances were found: naphthalene derivatives for pot marigold, furan derivatives for trifid bur-marigold and burnet, and the specific terpenoids for licorice, milfoil, and wild marjoram. All the plants used in the herb mixture, except for pot marigold and cinquefoil, were analyzed (ion-exclusion chromatography) for the content of lower carboxylic acids. It was established that the specific acids for the wild marjoram and licorice are ascorbic and the succinic acids, respectively.

Increasing the solubility of phenazepam by forming solid dispersions

The effect of solid dispersion (SD) formation on the solubility of phenazepam has been studied. Phenazepam and its SDs with poly(ethyleneglycol)-1500 (PEG), poly(vinylpyrrolidone)-10000 (PVP), and β-cyclodextrin were studied. The SD with PVP increases both the solubility and the dissolution rate of phenazepam. Results obtained by a complex of physical and chemical methods suggest that the improved release of phenazepam from the SD with PVP is due to solubilization, amorphization, and formation of a colloidal dispersion of the parent drug substance.

Increasing the solubility of an angioprotector by the method of solid dispersions

The effect of solid dispersions (SDs) on the solubility of parmidin has been studied by comparing the solubility of parmidin, its SDs, and physical mixtures with polyethyleneglycol-1500, polyvinylpyrrolidone-10000, and β-cyclodextrin. It is established that the formulation of SDs increases the solubility and the dissolution rate of parmidin. Data obtained using a complex of physical and chemical methods suggest that improvement of the drug release from SDs is due to the solubilization and the formation of a colloidal-dispersion state of the given substance.

Determining Caprylate Ions in a 10% Albumin Solution for Infusions by Ion-Exclusion Chromatography

Previously [1, 2], it was demonstrated that ion-exclusion chromatography (IEC) — a variant of high-performance liquid chromatography (HPLC) — provides for effective, accurate, and rapid determination of biologically active organic carboxylic acids in objects such as infusion solutions and blood preservatives. The group of studied compounds included citric, acetic, and fumaric acids, which are contained in the medicinal preparations (objects) predominantly in the form of salts. The proposed method is capable of detecting maleic acid — a toxic impurity, the presence of which in the infusion solutions is inadmissible. Using IEC, it is possible to detect maleic acid in infusion solutions even in small amounts. This is important, in particular, for evaluation of the safety of infusion solutions such as mafusol. This paper addresses the determination of caprylic acid (C8), which is added in the form of sodium caprylate (stabilizing agent) to the hemopreparation called a “10% albumin solution for infusions.” As is known, caprylic acid is strongly retained on ion exchangers and its motion through a chromatographic column is determined to a considerable extent by hydrophobic interactions. It was pointed out [3, 4] that the contribution of this effect to the chromatographic behavior of long-chain acids (beginning with caprylic acid) exceeds the contributions due to the Donnan exclusion and the sieve effect. These three factors determine the retention of carboxylic acids in IEC [5]. To our knowledge, data on the determination of caprylic acid were never reported in the domestic or international literature. This is probably related to the fact that this compound is rarely used in industry, while basic research is usually restricted to considering caprylic acid within the framework of the problem of retention of long-chain carboxylic acids [6]. The aim of this study was to develop a chromatographic procedure for determining sodium caprylate in preparations of 10% albumin solution for infusions. This is important in view of the rather high toxicity of caprylate, which makes undesirable an increase in the content of this substance above a certain permissible level.

Citrate and Acetate Ions Determined in Blood Preservatives and Infusion Solutions by Ion-Exclusion Chromatography

Since the discovery in 1975 [1], the process of ion chromatography has proved to be a rapid, sensitive, and selective method for determining both inorganic and organic acids. Initially, the development of ion chromatography was related to the use of various anion-exchange resins. However, the appearance of fine-grained polymeric materials stable with respect to high pressures and pH variations made it possible to employ a variant known as ion-exclusion chromatography (IEC). Presently, the IEC determination of organic acids is based on the use of sulfided styrene-butadiene – benzene copolymers. The anions of strong acids exhibit repulsion from negatively charged sulfonic groups grafted on the matrix surface and are eluted with the “dead” volume, while the molecules of weakly ionized acids are retained in the column. Besides the ion exclusion proper, other factors influencing the retention may include the so-called sieve effects and hydrophobic interactions. Despite some attempts [2], the contributions of various factors are rather difficult to estimate. The choice of acids as eluents is explained by the wish to provide for the maximum conversion of weak acids into a molecular form. The advantages of acid eluents were originally demonstrated by Turkelson and Richards [3]. Early works, performed using water as the eluent, gave chromatograms with relatively broad and asymmetric peaks. This is explained by the fact that any acid may exist both in the molecular form and in the form of a combination of various ions. In modern chromatography, elution with water is employed only for demonstrating the advantages of other eluents [4, 5]. We selected benzoic acid as the eluent for chromatography with a conductometric detector, in particular, because of its low conductivity [6]. Sulfuric acid, employed in the system with a UV detector, was also employed in some IEC analyses [5, 7 – 9]. The advantages of this eluent are the stability of properties, availability, and the absence of absorption bands of sulfate anions in the visible spectral range. The main detectors for IEC are those of the conductometric and UV types, both employed in our experiments. A conductometric detector measures the change in the electric conductivity of the eluent passing through the cell, while a UV detector measures the optical absorption signal [10]. Pharmaceutical preparations have been studied by IEC for a long time. The quality of blood preservatives in many countries is monitored by HPLC and this method is included in many pharmacopoeias [11]. In Russia, these analyses are still performed by titration methods [12 – 14]. Taking into account the development of infusion therapy and an increase in production of the corresponding preparations, the present state of the quality control can no longer be considered as satisfactory [15]. Analysis of pharmaceutical preparations of this group requires urgent development of appropriate methods. The aim of this study was to assess the possibility of using IEC for the analysis of blood preservatives and infusion solutions. In particular, we will consider the procedures of determining citrate and acetate ions in multicomponent compositions and demonstrate the principal possibility of jointly determining citrate ions and glucose in blood preservatives.

FUMARATE IONS IN MAFUSOL INFUSION SOLUTION DETERMINED BY ION-EXCLUSION CHROMATOGRAPHY

Ion-exclusion chromatography (IEC) is a variant of high-performance liquid chromatography (HPLC), which provides for selective and rapid determination of organic acids with high sensitivity [1]. Previously [2], we have demonstrated good prospects in using IEC for the detection of citrate and acetate ions in blood preservatives and infusion solutions. Another problem of considerable practical interest is the determination of fumaric acid and its toxic isomer – maleic acid – in infusion solution of complex compositions. Fumaric acid is a relatively rare object in chromatographic investigations reported in international and domestic literature [3]. Turkelson and Richards [4] justified the choice of acid eluents as the mobile phase and presented some analytical characteristics for determining fumarate ions in biological fluids and fruit juices. Chen and Adams [5] pointed out the rather low detection threshold of fumarate ions as compared to that of acetate and citrate ions. The aim of this study was to develop a chromatographic procedure for determining fumarate ions in mafusol preparation (infusion solution). The titrimetric method [6] presently used for this purpose is laborand time-consuming and still insufficiently sensitive.