Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use

Cefixime (CEF) is a cephalosporin included in the WHO Model List of Essential Medicines for Children. Liquid formulations are considered the best choice for pediatric use, due to their great ease of administration and dose-adaptability. Owing to its very low aqueous solubility and poor stability, CEF is only available as a powder for oral suspensions, which can lead to reduced compliance by children, due to its unpleasant texture and taste, and possible non-homogeneous dosage. The aim of this work was to develop an oral pediatric CEF solution endowed with good palatability, exploiting the solubilizing and taste-masking properties of cyclodextrins (CDs), joined to the use of amino acids as an auxiliary third component. Solubility studies indicated sulfobutylether-β-cyclodextrin (SBEβCD) and Histidine (His) as the most effective CD and amino acid, respectively, even though no synergistic effect on drug solubility improvement by their combined use was found. Molecular Dynamic and 1H-NMR studies provided insight into the interactions of binary CEF:His and ternary CEF:His:SBEβCD systems used to prepare CEF solutions, which resulted stable and maintained unchanged antimicrobial activity during the two-weeks-use in therapy. The ternary solution was superior in terms of more tolerable pH (5.6 vs. 4.7) and better palatability, being resulted completely odorless by a panel test.

Modeling of the reaction interdiffusion in the polycrystalline systems with limited component solubility

that may be accompanied by the processes of mutual diffusion and phase formation. Controlled technological process of forming coatings with the given properties entails the necessity of forecasting the evolution of the phase composition. This in turn requires the development of algorithms and quantitative models of the processes. Reactive mutual diffusion in polycrystalline metal (oxide film systems with limited component solubility) has not been simulated before. The simulation allows selecting the annealing conditions (time and temperature) necessary for the inclusion and uniform distribution of metal in the oxide lattice. A quantitative model of the interaction in a multi-layer system metal — polycrystalline oxide of the other metal under conditions of limited solubility is developed. The model is based on the concepts of mutual diffusion of the components and the bulk reactions of the formation of complex oxides. The developed model was applied to the analysis of the process of modifying thin films of titanium oxide with transition metals. The model allowed us to perform a numerical analysis of the experimental concentrations of the component distributions in polycrystalline Co - Ti02 and Fe - Ti02 thin-film systems. The individual diffusion coefficients of the studied metals and titanium under conditions of vacuum annealing were determined. The model provides a good description of the basic systematic features of the process: the appearance of titanium in the metal film and deep penetration of Fe and Co into the film of titanium oxide. It also explains the fact that complex oxides are formed not by layer-by-layer growth at the metal-oxide interface, but throughout the entire thickness of Ti02 film. The results of analysis of the processes of interracial interaction in layered systems accompanied by the reaction mutual diffusion can be used to predict the evolution of the phase composition, as well as to control the technological processes of obtaining materials with the desired properties.

Constructing Isotherms of Oxygen Solubility in the Liquid Metal of the Cu-Na-K-O System

The thermodynamic modeling of phase equilibria in the liquid metal of the Cu–Na–O, Cu–K–O and Cu–Na–K–O systems in the temperature range of 1100–1300 °С was done. The calculations were performed using the methodology of constructing a surface of component solubility in the metal melt, which does not only allow us to calculate the isotherms of oxygen solubility in the molten metal, but also to link the changes in the composition of such molten metal with quality changes in the composition of the interaction products. The isotherms of the oxygen solubility in the liquid metal of the Cu–Na–O, Cu–K–O and Cu–Na–K–O systems were constructed.

APPLICATION OF SOLID DISPERSION TECHNIQUE IN SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF NATEGLINIDE

Objective: Nateglinide (NTG) is a potent short-acting biopharmaceutical classification system class II antidiabetic medication. The primary objective of the present investigation was to prepare and evaluate solid dispersions of NTG to enhance the component solubility and immediate release (IR) profile. The secondary objective was to formulate sustained release (SR) matrix layer of NTG for prolonging its effect in the body and to decrease oscillations in plasma concentration level.Methods: NTG (270 mg) SR layer was formulated using release retardant polymers such as Carbopol, ethyl cellulose (EC), hydroxy EC, hydroxypropyl methylcellulose (HPMC), Kollidon, and locust bean gum at concentrations of 15% and 30%. IR layer of NTG (60 mg) was formulated using drug: Polymer inclusion complexes (1:1 and 1:2) of β-cyclodextrin (CD), HP β-CD, polyvinylpyrrolidone (PVP) K-15, and PVP K-30 by physical mixing and kneading methods (KMs).Results: Among the all the carriers tested HP β-CD at 1:2 ratio prepared by KM (I3) gave highest enhancement of dissolution rate and dissolution efficiency with acceptable f1 (10.5) and f2 (51.0) values in comparison to marketed IR tablets (Starlix-60®). The SR formulation S12 was able to show a minimum amount of drug release (15%) within 1 hr comparatively, with a complete and sustained effect on drug release.Conclusion: Thus, HPMC K-100M at a concentration of 30% in the SR layer in combination with HP β-CD (1:2) solid dispersions in the IR layer may be used in the design of oral controlled drug delivery system for NTG.

Pengaruh komposisi beberapa glass fiber non dental terhadap kelarutan komponen fiber reinforced composites

The effect of composition glass fiber non dental on water solubility of fiber reinforced composites. E glass fiber dental is one of the most used dental fibers in several applications in the dental field. However, the available of E glass fiber dental in Indonesia is very limited. A variety of types of non-dental glass fiber material is easily found as the materials engineering. The purpose of the study was to evaluate the effect of composition non dental glass fiber on the component solubility of FRC. The materials used in the research was E glass fiber dental (Fiber splint, Polydentia SA, Switzerland), composition A non-dental glass fiber (LT, China), composition B (CMAX, China), composition C (HJ, China), flowable composite (Charmfill Flow, Denkist, Korea) and silane coupling agent (Monobond S, Ivoclair Vivadent, Liechtenstein). The subject was divided into 4 groups. Component solubility test was based on the ISO 4049. The result was then analyzed with one way ANOVA (α=0,05). The result of the research showed that on the average percentage of the solubility (%), the lowest was on the group of E glass fiber dental (0.476±0.03) and the highest was on the non dental glass fiber C (0.600±0.01). The result of the one way ANOVA test showed a significant difference between the compositiom fiber on the component solubility. The conclusion the research was that low content of Na2O K2O, CaO and MgO decreased the component solubility of FRC.ABSTRAKE glass fiber dental adalah fiber yang sering digunakan di kedokteran gigi. Ketersediaan E glass fiber di Indonesia masih sangat terbatas. Berbagai jenis bahan glass fiber non dental banyak ditemukan dipasaran sebagai material engeenering dengan harga yang relatif murah sehingga diharapkan dapat digunakan sebagai alternatif pengganti E glass fiber dental. Komposisi glass fiber non dental hampir sama dengan E glass fiber dental. Komposisi berpengaruh terhadap sifat mekanis dan sifat-sifat kimia fiber. Komposisi glass fiber seperti Na2O dan K2O akan meningkatkan ketahanan terhadapap air. Tujuan dari penelitian ini adalah mengetahui pengaruh komposisi glass fiber non dental terhadap kelarutan komponen. Bahan yang digunakan dalam penelitian ini adalah E glass fiber dental (Fiber-splint, Polydentia SA, Switzerland), glass fiber non dental komposisi A (LT, China), komposisi B (CMAX, China), komposisi C (HJ, China), flowable komposit (CharmFill Flow, Denkist, Korea) dan silane coupling agent (Monobond S, Ivoclar Vivadent, Liechtenstein). Subjek dibagi dalam 4 kelompok untuk dilakukan uji kelarutan berdasarkan ISO 4049. Hasil yang diperoleh dianalisis menggunakan ANAVA satu jalur (a = 0,05). Hasil penelitian menunjukkan rerata kelarutan komponen (%) yang terendah pada kelompok E-glass fiber dental (0,476±0,03) dan hasil tertinggi pada glass fiber non dental C (0,600±0,01). Hasil uji Anava satu jalur menunjukkan perbedaan yang bermakna antara komposisi fiber pada kelarutan komponen (p<0,05). Kesimpulan penelitian adalah komposisi Na2O dan K2O serta CaO dan MgO yang rendah dapat menurunkan sifat kelarutan komponen dari fiber reinforced composites.