Anna Froelich

Application of gellan gum in pharmacy and medicine

Over the past few decades, microbial polysaccharides have been under intense investigation due to their advantageous physicochemical properties. A great structural diversity of these biomolecules has led to multiple applications in food industry, personal care products, pharmacy and medicine. Currently, one of the most widely studied and fully described member of this group is gellan. It is a linear polymer produced by Sphingomonas elodea. A polymer chain of gellan consists of a tetrasaccharide repeating unit of l-rhamnose, d-glucose and d-glucuronate. So far most of the studies have been focused on the application of gellan as a food ingredient. However, due to the unique structure and beneficial properties, gellan is currently described as a potent multifunctional additive for various pharmaceutical products. Specific gelling properties in different media led to the development of controlled release forms based on gellan. Various formulations have been studied including oral, ophthalmic, nasal and other. Recent reports suggest that gellan-based materials can also be used in regenerative medicine, stomatology or gene transfer technology.

Oleanolic acid ethanol monosolvate.

Crystals of the title compound (systematic name: 3β-hydroxyolean-12-en-28-oic acid ethanol monosolvate), C30H48O3·C2H5OH, were obtained from unsuccessful co-crystallization trials. The asymmetric unit contains two symmetry-independent oleanolic acid molecules, as well as two ethanol solvent molecules. Intermolecular O—H⋯O hydrogen bonds stabilize the crystal packing. In the oleanolic acid molecules, ring C has a slightly distorted envelope conformation, while rings A, B, D and E adopt chair conformations and rings D and E are cis-fused. Both independent ethanol molecules are orientationally disordered [occupancy ratios of 0.742 (8):0.258 (8) and 0.632 (12):0.368 (12).

Novel microemulsion-based gels for topical delivery of indomethacin: Formulation, physicochemical properties and in vitro drug release studies

HYPOTHESIS Microemulsion-based semisolid systems may be considered as an interesting alternative to the traditional dosage forms applied in topical drug delivery. Mechanical properties of topical products are important both in terms of application and dosage form effectiveness. In this study we designed and evaluated novel microemulsion-based gels with indomethacin and analyzed the factors affecting their mechanical characteristics and drug release. EXPERIMENTS The impact of the microemulsion composition on the extent of isotropic region was investigated with the use of pseudoternary phase diagrams. Selected microemulsions were analyzed in terms of electrical conductivity and surface tension in order to determine the microemulsion type. Microemulsions were transformed into polymer-based gels and subjected to rheological and textural studies. Finally, the indomethacin release from the analyzed gels was studied and compared to commercially available product. FINDINGS The extent of isotropic domain in pseudoternary phase diagrams seems to be dependent on the polarity of the oil phase. The surface tension and conductivity monitored as a function of water content in microemulsion systems revealed possible structural transformations from w/o through bicontinuous systems into o/w. The mechanical properties of semisolid microemulsion-based systems depended on the composition of surface active agents and the drug presence. The drug release profiles observed in the case of the investigated gels differed from those recorded for the commercially available product which was most probably caused by the different structure of both systems.

Rheological and textural properties of microemulsion-based polymer gels with indomethacin

Abstract In this paper, we present novel microemulsion (ME)-based semisolid polymer gels designed for topical administration of poorly water soluble non-steroidal anti-inflammatory drugs. Indomethacin (IND) was used as a model compound. The ME consisted of castor oil, water, Tween®80 as a surfactant and ethanol as cosurfactant. To obtain the desired consistency of the formulations Carbopol®960 was applied as a thickening agent. The aim of the study was to analyze in detail the mechanical properties of the obtained systems, with special attention paid to the features crucial for topical application. The rheological and textural experiments performed for samples with and without the incorporated drug clearly indicate that flow characteristics, viscoelastic properties and texture profiles were affected by the presence of IND. Novel semisolid formulations with IND described for the first time in this paper can be considered as an alternative for commercially available conventional topical dosage forms.

Novel organogels for topical delivery of naproxen: design, physicochemical characteristics and in vitro drug permeation

Abstract Taking into account possible irritation of the skin upon contact with naproxen (NPX) crystals and lower bioavailability after administration of the suspended or ionized drug, the aim of the work was to design and characterize novel and easy-to-formulate gels with the entirely dissolved drug in the acidic form. The formulations contained ethanol, SynperonicTMPE/L 62 and Arlasolve® DMI or Transcutol®. Carbopol®940 was used as the thickener. The properties of organogels were compared with six market products. The rheological measurements included steady flow experiments and oscillatory analysis. The texture profile analysis was conducted to calculate the mechanistic parameters. The in vitro permeation studies were performed on SOTAX CE 7 smart apparatus with the application of Strat-M artificial membranes. The obtained organogels fulfilled the requirements for topical products in terms of consistency, uniformity, stability, drug dissolution and permeation. The permeation studies revealed distinct differences among the commercial hydrogels according to permeation coefficients (kP), drug flux (Jss) and average cumulative amount of NPX per area after 12 h (Q12h). The presented work clearly shows that the organogels can be proposed as an alternative for commercial products where NPX occurs in the form of crystals.

pH-Dependent Behavior of Novel Gellan Beads Loaded with Naproxen

BACKGROUND Oral administration of non-selective COX inhibitors involves the risk of serious side-effects. In the case of naproxen (NPX), the most frequent are those related to malfunctioning of the gastric mucosa. On the other hand, NPX and other NSAIDs are extensively studied in terms of colorectal cancer (CRC) prevention and inhibition, since it has been evidenced that COX-2 corresponds with the risk of the tumor occurrence and growth. Both side-effects in the stomach and possible antitumor activity of NPX justify the attempts to search for novel carriers for NPX with the site specific release in the colon. Thus, the aim of the work was to design, formulate and characterize low-acyl gellan gum (GG) macro beads as potential carriers for the delivery of NPX to the distal parts of the gastrointestinal tract. METHODS The beads were obtained by the ionotropic gelation technique. CaCl2 solution was used as a cross-linking medium. After production, the beads were dried and used for further experiments. First, pure NPX and the beads were evaluated by Raman spectroscopy and DSC studies. The surface and morphology of the beads were analyzed by SEM. Next, the drug encapsulation efficiency and content in the beads were determined. The swelling and degradation behavior of the beads were evaluated in four simulated gastrointestinal fluids at different pH (1.2; 4.5; 6.8 and 7.4). The NPX in vitro release studies were conducted on USP I apparatus (rotating basket) at pH=7.4 and compared to the commercial enteric tablet. RESULTS The polymer content of 0.5 % was considered as too low to obtain spherical beads in the dried form. Raman spectra confirmed that NPX did not undergo structural changes during production process. DSC studies showed that thermal decomposition at lower temperatures was observed for formulations with the lowest amount of GG. It turned out that the most important factor which determined the morphology of the beads was the amount of gellan gum in the initial mixture. The beads revealed 13.9- 39.9% of drug loading and 75.3-99.7% drug encapsulation efficiency. Swelling of the beads was pHdependent as the beads remained stable in the acidic environment but started to absorb water. In pH=7.4 after 3 hours, the beginning of the physical decomposition of the polymer matrix was observed. The drug release studies showed that in pH=7.4 the commercial tablets released 90% of the drug after 45 minutes while the amount of NPX released from pellets after the same time was 40-80%. CONCLUSION In general, it can be stated that gellan macro beads may be regarded as suitable for site specific delivery of NPX to the colon. However, these simple to obtain beads can be potentially used as carriers for many different drugs whenever it is necessary to omit the stomach.

(E)-17β,19-Epoxy­methano-17,23,24-tridemethyl-4-nor-5β,18α-olean-3-one oxime

In the pentacyclic triterpenoide skeleton of the title molecule, C27H43NO2 [systematic name: (3E,3aS,5aR,5bR,7aR,11R,11aR,11bR,13aR,13bR)-5a,5b,10,10,13b-pentamethylicosahydro-1H-11,7a-(epoxymethano)cyclopenta[a]chrysen-3-one oxime], the five-membered ring A has an envelope conformation, while the six-membered rings B–E adopt chair conformations. Rings A and B are cis-fused. The hydroximino group has an E configuration. Strong intermolecular O—H⋯O hydrogen bonds link the molecules into helical chains.

Rheological investigation of high-acyl gellan gum hydrogel and its mixtures with simulated body fluids:

Purpose Most of the studies concerning gellan have been focused on its application as a food ingredient, however, gellan is often considered as a candidate for the development of novel pharmaceutical formulations. Taking into account that gellan is ion-sensitive, it can be assumed that its initial mechanical properties can change upon contact with body secretions. Therefore, the aim of the work was to investigate the rheological properties of pure high-acyl gellan gum hydrogel (0.4%) and its mixtures with selected simulated body fluids. Methods The rheological investigations were performed on rotational rheometer and included oscillatory temperature, amplitude, and frequency sweeping. The results enabled estimation of the linear viscoelastic regime, calculation of the cross-over points, and percentage of structure recovery. Results In the case of pure hydrogel no evidence of thermosensitivity was observed in the range of 20–40°C. In pH = 1.2 (NaCl/HCl) the hydrogel structure was almost entirely destroyed. Mixing with phosphate buffer (pH = 4.5) resulted in higher gel strength than after dilution with deionized water. The opposite effect was observed in the case of pH = 7.4. The studies performed for the mixture of GG hydrogel and mucin indicated interaction between the components. The hydrogel elasticity increased in the presence of simulated tear, but decreased in simulated saliva and vaginal fluid. Conclusions In this study, it was shown that the stability of a three-dimensional gellan structure may be affected by pH and the presence of mucin which most probably competed with gellan gum in divalent cations binding. The observations presented in this study may be important in terms of potential application of gellan gum as a potential carrier in drug delivery systems.

Gellan gum macrobeads loaded with naproxen: The impact of various naturally derived polymers on pH-dependent behavior

Aims After oral administration, naproxen generates several side-effects related to stomach malfunction. Undoubtedly, the enteric dosage forms with naproxen can be considered as safer. Moreover, since it has been evidenced that development and growth of colorectal cancer is related to the presence of cyclooxygenase, naproxen is investigated in terms of the tumor prevention. The aim of the present work was to formulate and evaluate the properties of novel naproxen-loaded macrobeads, made on the basis of low-acyl gellan gum and its blends with carrageenans, guar gum, cellulose sulfate, and dextran sulfates. Method Seven formulations were prepared by ionotropic gelation. The morphology of the dried beads was evaluated by scanning electron microscopy. The next step focused on Raman spectroscopy and thermal analysis of naproxen, polymers, and the beads. Next, the swelling behavior was examined in three acceptor fluids at pH = 1.2; 4.5, and 7.4. The beads were evaluated regarding naproxen content and encapsulation efficiency. The last stage of the work concerned the drug release studies. Results Addition of any other polysaccharide than gellan resulted in flattening of the beads upon drying. Differential scanning calorimetry confirmed the crystalline form of naproxen. Raman spectra showed that no apparent interactions occurred. In the acidic environment, all the beads revealed the tendency to absorb water. The beads swelled to the greatest extent at pH = 4.5. Naproxen was released from the beads at a varied rate. At pH = 7.4, the most prolonged release was observed for the beads containing carrageenans. Conclusions We have proved that blending of gellan with various polysaccharides can change the pH-dependent properties of the beads loaded with naproxen. We believe that the information enclosed in the paper will be of particular importance regarding the development and characteristics of novel oral dosage forms based on natural polymers.

Design and characteristics of gellan gum beads for modified release of meloxicam

Abstract The aim of the presented work was to design, formulate and evaluate the properties of low-acyl gellan macro beads with the potential application as carriers for oral delivery of meloxicam (MLX) in the prophylaxis of colorectal cancer. The beads were obtained by means of ionotropic gelation technique. Calcium chloride (1.0%, 9.0 × 10−2 M) was used as the cross-linking agent. Nine different polymer, drug and surfactant (Tween®80) mixtures were used for production of the beads. The quantitative compositions of the mixtures were generated with the application of the Design of Experiments (DoE) modulus from the STATISTICA Software. The prepared formulations revealed 7.2–27.0% of drug loading and 29.2–50.7% drug encapsulation efficiency. It turned out that 0.5% amount of gellan gum in the mixtures was not sufficient to obtain spherical beads. The morphology and surface of the dried beads were analyzed by SEM. Raman spectra confirmed that MLX did not undergo structural changes during production of the beads. The swelling behavior and degradation of the beads were evaluated in three simulated gastrointestinal fluids at different pH (1.2; 4.5; 6.8). The MLX in vitro release studies were conducted on USP apparatus IV, working in the open loop mode. The obtained results showed that MLX release from the dried beads was pH-dependent. The formulations obtained from mixtures containing 1.0 and 1.5% of gellan may be considered as oral dosage forms for MLX, intended to omit the stomach and release the drug in the distal parts of the gastrointestinal tract.