An optimized commercially feasible milling technique for molecular encapsulation of meloxicam in β-cyclodextrin

Background: The practical applicability of solid dispersions (SD) for improvement of oral bioavailability of poorly water-soluble drugs has still remained limited because of lack of feasibility for scale-up of manufacturing processes. The present research work deals with the preparation of SDs of meloxicam (MLX) with β-cyclodextrin (β-CD) by the ball-milling technique to overcome the scale-up issues.

Methods: Phase-solubility studies were conducted to analyze the influence of β-CD on solubility of MLX. In vitro dissolution studies on various complexes as well as tablets prepared on pilot scale in an industrial set up were performed and compared with the marketed products. Physicochemical characterization of optimized complexes was done using various methods to study drug-β-CD interaction.

Results: Solubility of pure MLX in water at 25°C was found to be only 9.4 µg/mL. The AL type of phase-solubility profile of MLX with β-CD [stability constant (K_1:1)?=?22.056?M^?1 and Gibbs free energy (ΔF^o)?=?–7.665 KJ/mole] confirmed the solubility enhancement capability of β-CD. Milling time of 6?h was considered to be optimum and showed maximum enhancement of drug dissolution. The amorphous nature of the milled complex and mode of interaction of MLX with β-CD was confirmed by differential scanning calorimetry (DSC), x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance spectrophotometry (¹HNMR). Tablets containing MLX-β-CD (1:1.5?M) milled complexes showed the best release (T_90%?=?10.94?min) compared to the marketed products (T_90% ≥ 450?min). Stability studies performed confirmed the integrity of the amorphous complex.

Conclusion: Stable inclusion complexes of MLX-β-CD with enhanced aqueous solubility and dissolution rate were prepared by a highly efficient and controlled large-scale milling technique.     

Exploiting H-induced lattice expansion in β-palladium hydride for enhanced catalytic activities toward oxygen reduction reaction

We have developed an efficient strategy to synthesize an active and durable electrocatalyst of Pd hy-dride nanocubes(NCs).Instead of the traditional chemical me...     

Synthesis of β-cyclodextrin functionalized gold nanoparticles for the selective detection of Pb2+ ions from aqueous solution

In the present study we carried out the synthesis of β-cyclodextrin (β-CD) functionalized gold nanoparticles (AuNPs) using a microwave assisted heating method in alkaline media. Stable dispersion of β-CD stabilized AuNPs was obtained at an optimized pH of 10.5. At this pH value the deprotonated secondary hydroxyl group of β-CD shows the highest chelating affinity toward Pb²⁺ ions thereby inducing AuNP aggregation. The Pb²⁺ induced aggregation in β-CD-AuNP solution is monitored by both colorimetric response and UV-Vis spectroscopy. TEM, DLS and FTIR analyses were carried out to confirm the Pb²⁺ ion induced aggregation behaviour of β-CD-AuNPs under alkaline conditions. Furthermore at the experimental pH the response of the β-CD-AuNP system towards Pb²⁺ ions is selective when compared with other interfering metal cations.     

Examination of the suitability of α-tocopherol as a stabilizer for ultra-high molecular weight polyethylene used for articulating surfaces in joint endoprostheses

The lifetime of articulating surfaces in joint endoprostheses made of ultra-high molecular weight polyethylene (UHMW-PE), especially of UHMW-PE-cups of hip-endoprostheses, is usually limited to 10–15 years due to material failure as a result of oxidation of the UHMW-PE in vivo. In this study the suitability of the natural antioxidant -tocopherol (vitamin E) as a stabilizer for UHMW-PE in these applications was investigated. Specimens with 0.1%, 0.2%, 0.4% and 0.8% w/w -tocopherol as well as unstabilized samples were sintered and sterilized with -rays at 25 kGy in accordance with standard processing methods of cups for total hip-endoprostheses. These specimens were aged in pure oxygen at 70 °C and 5 bar as well as in aqueous H₂O₂ at 50 °C. The degree of oxidation was observed by means of FTIR-spectroscopy, DSC analysis and mechanical testing. The FTIR-measurements showed that -tocopherol can prolong the lifetime of UHMW-PE in an oxidative environment by a factor of more than 2.5. In the mechanical tests no embrittlement could be observed with the stabilized samples. A comparison with the standard antioxidant system Irganox® 1010/Irgafos® 168 (Ciba-Geigy, Switzerland) was carried out and revealed that -tocopherol can even exceed the stabilization effect of this widely-used antioxidant system.     

Formulation of ternary complexes of glyburide with hydroxypropyl-β-cyclodextrin and other solubilizing agents and their effect on release behavior of glyburide in aqueous and buffered media at different agitation speeds

Glyburide, a sulfonylurea derivative, widely used as hypoglycaemic agent. In the present study, an attempt has been made to investigate the most effective third component which can be used with hydroxylpropyl-β-cyclodextrin (HPβCd) to form a ternary complex with glyburide in order to enhance its dissolution rate, as well as reduce the amount of HPβCd used for formulating the binary complex with glyburide. Moreover, the objective of this study was also to develop a discriminatory dissolution media in order to discriminate the effect of the different solubilizing agents used for formulating the ternary complex system. Sodium lauryl sulphate, Poloxamer-188, Polyvinylpyrrolidone K-30, lactose and l-arginine were used to formulate ternary system along with HPβCd and glyburide. The ternary system formulated with glyburide:HPβCd:l-arginine in a proportion of 1:1:0.5 has shown the fastest dissolution rate when compared to other solubilizing agents. Unbuffered aqueous media with stirring speed 50?rpm has produced the most discriminatory dissolution profiles. The DSC thermograms and the powder X-ray analysis revealed the decrease in crystallinity of the drug. This was an indication of amorphous solid dispersion or molecular encapsulation of the drug into the cyclodextrin cavity.     

Formulation of ternary complexes of glyburide with hydroxypropyl-β-cyclodextrin and other solubilizing agents and their effect on release behavior of glyburide in aqueous and buffered media at different agitation speeds

Glyburide, a sulfonylurea derivative, widely used as hypoglycaemic agent. In the present study, an attempt has been made to investigate the most effective third component which can be used with hydroxylpropyl-β-cyclodextrin (HPβCd) to form a ternary complex with glyburide in order to enhance its dissolution rate, as well as reduce the amount of HPβCd used for formulating the binary complex with glyburide. Moreover, the objective of this study was also to develop a discriminatory dissolution media in order to discriminate the effect of the different solubilizing agents used for formulating the ternary complex system. Sodium lauryl sulphate, Poloxamer-188, Polyvinylpyrrolidone K-30, lactose and l-arginine were used to formulate ternary system along with HPβCd and glyburide. The ternary system formulated with glyburide:HPβCd:l-arginine in a proportion of 1:1:0.5 has shown the fastest dissolution rate when compared to other solubilizing agents. Unbuffered aqueous media with stirring speed 50?rpm has produced the most discriminatory dissolution profiles. The DSC thermograms and the powder X-ray analysis revealed the decrease in crystallinity of the drug. This was an indication of amorphous solid dispersion or molecular encapsulation of the drug into the cyclodextrin cavity.     

Tests of biocompatibility of α-tocopherol with respect to the use as a stabilizer in ultrahigh molecular weight polyethylene for articulating surfaces in joint endoprostheses

To inhibit the oxidation in vivo of hip-cups made of ultrahigh molecular weight polyethylene (UHMW-PE), the natural antioxidant -tocopherol was added to the polymer. The added -tocopherol may however undergo chemical transformations during manufacturing and sterilization by -irradiation of hip-cups which may differ from human metabolism. Therefore, the question of the biocompatibility of the respective transformation products was investigated on test samples, which were prepared under the same conditions as applied for the production and sterilization of hip-cups. Thin plates (25×18×2 mm³) were fabricated out of test samples to investigate the cytotoxic activity according to EN 30993-5. In cytotoxicity testing, proliferation, mitochondrial activity and membrane integrity were not influenced by the material. In contrast, cell adhesion and cell spreading were diminished as shown with hemalum staining. In order to investigate the genotoxicity, the -tocopherol and its transformation products were extracted from test specimens by n-heptane at 185 °C under nitrogen atmosphere. Then the n-heptane was evaporated in vacuo and the remaining -tocopherol and its transformation products were dissolved in DMSO. The genotoxicity of this extract was then tested by the Ames-test according to DIN UA 12 (1995), which showed no indication for genotoxic activity.     

Cu(II), Co(II) and Ni(II) complexes of –Br and –OCH<Subscript>2</Subscript>CH<Subscript>3</Subscript> substituted Schiff bases as corrosion inhibitors for aluminium in acidic media

A group of Cu(II), Ni(II) and Co(II) complexes of –Br and –OCH₂CH₃ substituted Schiff bases as a new class of corrosion inhibitors for aluminium has been studied in 0.1 M HCl by the addition of 10 ppm compound using potentiodynamic polarization, electrochemical impedance spectroscopy, linear polarization methods and gas evolution tests at 25 °C. The inhibition efficiencies obtained from all methods employed are in good agreement. Results show Ni(II) complex of –OCH₂CH₃ substituted Schiff bases was the best inhibitor with a mean efficiency of 69% at 10 ppm additive concentration. The potentiodynamic polarization curves showed both the cathodic and the anodic processes of aluminium corrosion were suppressed, and the Nyquist plots of impedance gave mainly a capacitive loop. Scanning electron microscopy (SEM) was done from the surface of the exposed sample indicating uniform film on the surface.