Kneading Methods Research Articles

Enhancement of Dissolution profile of poorly water soluble drug using Water Soluble Carriers

Teneligliptin Hydrobromide is a long-acting, orally bioavailable, pyrolidone anti-diabetic activity with a solubility of 1.7mg/ml in water which also depends upon the pH and temperature of the solvent. So, Solid dispersion of drug with different polymers an attempt was made to improve dissolution of teneligliptin hydrobromide. The aim of this study was to prepare, characterize and compare solid dispersions of poorly water soluble anti diabetic drug by using PVP and HPMC for enhancing the dissolution rate of the drug. The solid dispersions were prepared by physical mixing method and kneading method at 1:1, 1:2 and 2:1 ratios of drug to polymer. The drug-excipient interaction study showed that the drug and polymers were compatible with each other. The formulations were evaluated for percent drug content, micromeritics and in-vitro dissolution studies. In the present study it was seen that there was an increase in in-vitro drug release for solid dispersion as compared to the pure drug taken alone. Based on the pattern of drug release, the kneading method showed more drug release as compared to physical mix method. In physical mix method, the rate of dissolution of teneligliptin hydrobromide was increased in teneligliptin and Polyvinylpyrrolidone (PVP) with the proportion of (1:2) when compared to the other formulations. In kneading method, the rate of dissolution of teneligliptin hydrobromide was increased in drug and Hydroxypropylmethylcellulose (HPMC) with the proportion of (1:2) when compared to the other formulations. Finally, solid dispersion containing HPMC, as a carrier, gave faster dissolution rates among all the formulations and was selected as the optimized formulation inthis study.

Molecular inclusion of Cymbopogon martinii essential oil with β-cyclodextrin as a strategy to stabilize and increase its bioactivity

An essential oil complex (EOP) of Cymbopogon martinii with β-cyclodextrin (β-CD) was evaluated as a strategy to stabilize the essential oil of Palmarosa and increase its bioactivity. The complexation methods used were co-precipitation and kneading, and, for comparison, physical mixing was carried out. To confirm the molecular inclusion, techniques were combined for the characterization of the inclusion complex, such as Fourier Transformer Raman Spectroscopy (FT-Raman), Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA), which suggested the formation of the EOP-β-CD complex with complexation efficiency through the co-precipitation and kneading methods of 77.68% and 47.74%, respectively. Stability of the free and complexed EOP in relation to major compounds (linalool, geraniol, geranyl acetate and caryophyllene) during 14 days of storage was analyzed through Headspace Gas Chromatography coupled with Mass Spectrometry. Geraniol showed stability over the period of evaluation and increased availability when complexed by the Co-precipitation and kneading complex. Furthermore, the antifungal and antitumor activity of the EOP-β-CD complex was evaluated, showing reduced mycelial growth against Aspergillus flavus and Fusarium verticillioides strains compared to the free EOP (percentage of inhibition to toxigenic fungi A. flavus EOP-KM: 29.41%; EOP-CP and EOP-PM: 24.37 and 14.28%, respectively, and, the free EOP with 11.76%). In addition, an interesting activity against tumor cells (HeLa and HT-29) was observed against the tested complexes, which emphasizes the importance of the biotechnological use of β-CD for the stability of natural compounds.

Development, optimization and characterization of hydrocolloid based mouth dissolving film of Telmisartan for the treatment of hypertension

Telmisartan, a BCS class II antihypertensive, has low oral bioavailability due to first-pass metabolism and a poor solubility profile, causing dissolving problems. Telmisartan is a suitable choice for the Rapid Release Drug Delivery System since it needs rapid absorption for a quick beginning of the activity. The goal of this research was to create and describe a solid dispersion employing hydrocolloid incorporated mouth dissolving film of Telmisartan. To make a Mouth Dissolving Film, first, prepare a solid dispersion using the Kneading Method, then use the Solvent Casting Metrpose of screening Carrier for the further formulation, solid dispersion is assessed for solubility, drug content, and drug release rate. The in-vitro drug release investigation revealed that solid dispersion had better solubility and rapid drug release than pure drug. Physical appearance, surface PH, thickness uniformity, disintegration duration, drug content uniformity, folding durability, and in-vitro drug release were among the physicochemical and mechanical parameters assessed on the produced films. A 32-level factorial design was used to improve the approach. The effects of film appearance, disintegrating time, and in-vitro drug release behavior on the composition of Film-forming polymer(hydrocolloids) and Super disintegration were investigated. The in-vitro drug release and disintegration time of the optimized batch were found to be 91.83 percent and 29 sec, respectively. These positive conclusions demonstrated that mouth dissolving film of Telmisartan can be formulated using HPMC E15 as a film-forming polymer and Sodium Starch Glycolate as a super disintegrant for improving bioavailability and therapeutic outcome.

Deep Adsorption Desulfurization of Fluid Catalytic Cracking Light Gasoline on NiO/ZnO-TiO2 Adsorbents with a High Breakthrough Sulfur Capacity.

Two kinds of NiO/ZnO-TiO2 adsorbents were prepared by equal volume impregnation (NiO/ZnO-TiO2-1) and kneading (NiO/ZnO-TiO2-2) methods. The adsorbents were characterized by X-ray diffraction, mercury intrusion porosimetry, scanning electron microscopy, energy dispersive X-ray spectroscopy, H2 temperature-programmed reduction, and H2 temperature-programmed desorption. It was found that NiO/ZnO-TiO2-2 had a smaller average pore diameter and a larger specific surface area as well as a more uniform distribution of the nickel element. Additionally, more Ni0 active sites together with a stronger interaction between the active component and the support were detected on the surface of NiO/ZnO-TiO2-2, which was beneficial to the inhibition of olefin saturation during desulfurization. The desulfurization performance of the adsorbents was investigated in a fixed bed reactor with fluid catalytic cracking light gasoline as a feed oil. The evaluation results confirmed NiO/ZnO-TiO2-2 with a better desulfurization performance with less olefin saturation. It could reduce the total sulfur content from 300 ppmw to less than 5 ppmw, and the breakthrough time and breakthrough sulfur capacity were 91 h and 6.71% (67.1 mg S/g adsorbent), respectively.

Manufacturing and Assessing the New Orally Disintegrating Tablets, Containing Nimodipine-hydroxypropyl-β-cyclodextrin and Nimodipine-methyl-β-cyclodextrin Inclusion Complexes.

The aim of the present study was to manufacture new orally disintegrating tablets containing nimodipine–hydroxypropyl-β-cyclodextrin and nimodipine–methyl-β-cyclodextrin inclusion complexes. For obtaining a better quality of the manufactured tablets, three methods of the preparation of inclusion complexes, in a 1:1 molar ratio, were used comparatively; namely, a solid-state kneading method and two liquid state coprecipitation and lyophilization techniques. The physical and chemical properties of the obtained inclusion complexes, as well as their physical mixtures, were investigated using Fourier transformed infrared spectroscopy, scanning electron microscopy, X-ray diffraction analyses, and differential scanning calorimetry. The results showed that the lyophilization method can be successfully used for a better complexation. Finally, the formulation and precompression studies for tablets for oral dispersion, containing Nim–HP-β-CD and Nim–Me-β-CD inclusion complexes, were successfully assessed.

Modified Solubility of Etodolac through Solid Dispersion and Complexation

Solubility and dissolution is an essential requirement for any drug to perform well in vivo. The present research was undertaken to enhance the dissolution rate of poor water soluble drug Etodolac through solid dispersion and complexation technique. Fusion method and kneading methods were employed for solubility enhancement by Solid Dispersion technique and complexation technique respectively. PEG-6000, HPMC K4M, β-Cyclodextrin and PVPK-30 are used as carriers. Physical mixtures were prepared in different ratio of drug and carriers. The prepared blends were evaluated for solubility, drug content, percent yield and drug release. Solubility enhancement was observed for all the experimental mixtures having maximum attainment for polymers PEG 6000 and PVPK-30. Pre and post enhancement Etodolac solubility values confirm the successful modification in solubility of drug through solid dispersion technique and complexation technique with slight edge toward complexation technique.

Pre-fibrillation of pulps to manufacture cellulose nanofiber-reinforced high-density polyethylene using the dry pulp direct kneading method

The dry pulp direct kneading method is an industrially viable, low-energy process for manufacturing cellulose nanofiber (CNF)-reinforced polymer composites, where the chemically modified pulps are nanofibrillated and uniformly dispersed in the polymer matrix during melt compounding. In the present study, cellulose fibers of various sizes ranging from surface-fibrillated pulps (20 μm in width) to fine CNFs (20 nm in width) were prepared from softwood bleached kraft pulps using a refiner and a high-pressure homogenizer. These cellulose fibers were modified with alkenyl succinic anhydride and dried. The dried fibers were used as a feed material for melt compounding in the dry pulp direct kneading method to fabricate CNF-reinforced high-density polyethylene (HDPE). When surface-fibrillated pulps were employed as a feed material, the pulps were nanofibrillated and dispersed uniformly in the HDPE matrix during melt compounding. The resulting composites had much better properties—i.e., much higher tensile modulus and strength values, and much lower coefficient of thermal expansion values—than the composites produced using pulps without pre-fibrillation. However, when CNFs were used as a feed material, they were shortened and agglomerated during melt compounding, and the properties of the composites consequently deteriorated. The study concludes that surface-fibrillated pulp, which can be produced cost-effectively using a refiner on an industrial scale, is more suitable as a feed material than CNFs for melt compounding in the dry pulp direct kneading method. This finding enables the elimination of a preliminary step in the preparation of CNFs from pulps, which is a time-consuming and energy-intensive process.Graphical abstract

Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization.

The objective of this study was to improve the dissolution and solubility of dexibuprofen (DEX) using hydroxypropyl beta cyclodextrin (HPβCD) inclusion complexes and also to evaluate the effect of presence of hydrophilic polymers on solubilization efficiency of HPβCD. Three different methods (physical trituration, kneading and solvent evaporation) were used to prepare binary inclusion complexes at various drug-to-cyclodextrin weight ratios. An increase in solubility and drug release was observed with the kneading (KN) method at a DEX/HPβCD (1:4) weight ratio. The addition of hydrophilic polymers poloxamer-188 (PXM-188) and poloxamer-407 (PXM-407) at 2.5, 5.0, 10.0 and 20% w/w enhanced the complexation efficiency and solubility of DEX/HPβCD significantly. Fourier-transform infrared (FTIR) analysis revealed that DEX was successfully incorporated into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) revealed less crystallinity of the drug and its entrapment in the cyclodextrin molecular cage. The addition of PXM-188 or PXM-407 reduced the strength of the DEX endothermic peak. With the addition of hydrophilic polymers, sharp and intense peaks of DEX disappeared. Finally, it was concluded that PXM-188 at a weight ratio of 10.0% w/w was the best candidate for improving solubility, stability and release rate of DEX.

Effects of different gelatinization degrees of potato flour on gluten network integrity and dough stickiness

Potato flour with different gelatinization degrees was prepared and the properties of potato flour - wheat flour dough were compared to investigate the reason why dough with more than 30 g/100 g potato flakes becomes sticky. The results showed that the water absorption capacity of potato flakes was the highest, which was 2.2-fold higher than that of gluten and 3.4-fold higher than that of wheat starch. Dough microstructure analysis indicated that competitive water absorption of potato starch and gluten protein led to the discontinuous gluten structure and more exposed gliadin which is responsible for dough stickiness. The gliadin content (obtained at a single elution) in potato flakes-wheat flour dough was 200–400 g/100 g higher than that of others. Two-step kneading method was applied to increase the gluten integrity and reduce gliadin leaching, which reduced the dough stickiness from 31.86 g to 23.07 g. This study demonstrated that the content of gliadin was more responsible for stickiness of the dough than gelatinized starch, and two-step kneading method can be employed to improve the properties of food prepared with potato flakes.

FORMULATION OF SOLID DISPERSIONS FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF SIMVASTATIN

Objective: The objective of the present work was to formulate the solid dispersions of simvastatin for enhancement of its aqueous solubility and dissolution rate.
 Methods: In the present study, solid dispersions of simvastatin were prepared by Kneading and Solvent evaporation methods. The polymeric carriers like Polyethylene glycol (PEG) 6000 and Polyvinyl Pyrrolidone (PVP) K30 were used in different ratios (ratio of drug: carrier was 1:1, 1:2) to formulate solid dispersions. The prepared solid dispersions were characterized by differential scanning calorimetry (DSC), Fourier transforms infrared spectroscopy (FTIR), and evaluated for drug content, percentage yield, saturation solubility, in vitro dissolution studies. The best formula of the solid dispersion was selected according to the solubility and dissolution data.
 Results: The F7 formulation was found to be an optimized formulation containing PVP K30 in the ratio 1:1 prepared by solvent evaporation technique. The Drug content was found to be higher i.e. 94.89 in the F7 batch. The FT-IR spectra revealed that there was no interaction between drugs and carriers. DSC thermogram indicated entrapment of simvastatin in PVP K30 and the conversion of crystalline simvastatin into an amorphous form. The F7 formulation showed maximum drug release i.e. 98.60% in 60 min which is 2 times greater than pure drug making it an optimized formulation.
 Conclusion: The solubility of simvastatin was successfully enhanced through the solid dispersion technique. Solid dispersions prepared with solvent evaporation method were more soluble than solid dispersions prepared with kneading method with carrier PVP K30.

STUDY THE RHEOLOGICAL AND OPTICAL PROPERTIES OF NICKELFERRITE /PMMA NOANO-COMPSITE GROWTH IN CRUDE OIL VIA LASER ABLATION

In this research the sample prepared in tow steps, the first step included prepared the sample to be ablated by using mixing kneading method formed as a Circular tablet contain Nickle Ferrite and Poly(methyl methacrylate)–(PMMA)polymer.Then the sample abated by using Nd:YAG laser with 1064 nm wavelength, 600 mJ energy, 6Hz frequency and 100 pulses for the tow sampleswhich immersed in dilute Crude Oil (obtained from the Rumaila Oil Field in Southern Iraq). The optical properties of samples showed thatthe same behavior but with blue shifting in S1 compared to other samples. The rheological properties showed that the viscosity increased as the polymer increased in two samples (S1 &S2) but the stability in the value of viscosity of the sample S1 that has low polymer ratio with temperature increased. The density of S1 almost double than S2 with same ablations' pulses.

Effect of mechanochemical inclusion of triamterene into sulfobutylether-β-cyclodextrin and its improved dissolution behavior

The formation of inclusion complexes between triamterene (TT) and cyclodextrins (CDs) to increase the water apparent solubility of TT was investigated. UV data showed that the binding constant of the TT/sulfobutylether-β-cyclodextrin (SBE-β-CD) inclusion complex was 510 L/mol. The phenyl ring of TT was inserted into the secondary hydroxy face of SBE-β-CD, as demonstrated by 1H-1H rotating frame nuclear Overhauser effect spectroscopy NMR. Physicochemical properties of solid TT/SBE-β-CD complexes prepared by physical mixing, kneading, freeze-drying, and mechanochemical methods were studied by X-ray diffraction and 13C cross-polarization and magic angle spinning NMR. With the mechanochemical method, the diffraction peak corresponding to TT disappeared, indicating the formation of an inclusion complex. The results of the dissolution test revealed that the solid complex obtained by the mechanochemical method improved the dissolution of TT. The water apparent solubility of TT can be improved by simple mechanical mixing without organic solvents, and improved bioavailability after oral administration is expected.

Chinese herb microneedle patch for wound healing

Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement. Attempts in this area tend to develop new forms to make their applications more convenient and wider. Here, we propose a novel Chinese herb microneedle (CHMN) patch by integrating the herbal extracts, Premna microphylla and Centella asiatica, with microstructure of microneedle for wound healing. Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold. Because the leaves of the Premna microphylla are rich in pectin and various amino acids, the CHMN could be imparted with medicinal efficacy of heat clearing, detoxicating, detumescence and hemostatic. Besides, with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica, the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant, anti-inflammatory and anti-bacterial activity. Taking advantages of these pure herbal compositions, we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria, inhibiting inflammatory, collagen deposition, angiogenesis and tissue reconstruction during the wound closure. These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.

FORMULATION AND EVALUATION OF SOLID DISPERSION TABLETS OF FUROSEMIDE USING POLYVINYLPYRROLIDONE K-30

Objective: The objective of the present study was to improve the aqueous solubility and dissolution characteristics of the loop diuretic furosemide (FUR); a class IV drug in the Biopharmaceutical Classification System (BCS) using solid dispersion technique.
 Methods: Solvent evaporation and kneading methods were used to produce solid dispersions of FUR in different ratios with the hydrophilic carrier polyvinylpyrrolidone K-30 (PVP-K30). The prepared solid dispersions were evaluated in terms of solubility study, percentage yield, drug content and Fourier transform infrared spectroscopic study (FT-IR). Tablets containing the optimized formula of solid dispersions ( were formulated and their dissolution characteristics were compared with commercial furosemide tablets.
 Results: The prepared solid dispersions showed an increase in aqueous solubility, especially those formulated in a 1:2 drug: carrier ratio using solvent evaporation method ( it showed a four-fold increase in solubility compared to the parent drug. The absence of drug-carrier chemical interactions that could affect the dissolution was proved by FT-IR. Solid dispersion tablets exhibited a better dissolution profile in simulated gastric fluid pH 1.2 at 37°C ± 0.5 than the commercial FUR tablets in terms of mean dissolution time (8.44 min) and dissolution efficiency in 30 min (42.54%). Both FUR solid dispersions and commercial tablets followed Weibull and Krosmeyer models as the two best models of drug release kinetics proving that they were immediate release.
 Conclusion: According to the results obtained in this study, solid dispersion techniques could be successfully used for the enhancement of aqueous solubility and dissolution rate of FUR.

Nanocellulose/polyethylene nanocomposite sheets prepared from an oven-dried nanocellulose by elastic kneading

Nanocellulose-reinforced polyethylene composite sheets were prepared with an in situ surface-hydrophobized, TEMPO-oxidized cellulose nanofibrils (TEMPO-CNFs) and polyethylene by thermal kneading with high shear forces (i.e., under ‘elastic’ kneading conditions). First, diethylene glycol (DEG) and cationic surfactant were added to a 1% TEMPO-CNF/water dispersion, and the mixture was agitated to prepare a foam. This foam was oven-dried at 40 °C for ~2 days to prepare a bulky and soft product. This oven-dried TEMPO-CNF/surfactant/DEG was added to maleic anhydride-modified polyethylene at 120–135 °C, and the mixture was elastically kneaded to prepare a TEMPO-CNF/surfactant/polyethylene master batch. The DEG and water molecules present in the oven-dried product were completely removed during kneading. The master batch was further kneaded with polyethylene to prepare TEMPO-CNF/cationic surfactant/polyethylene composite sheets. No detectable aggregates of TEMPO-CNFs were observed in the scanning electron microscopy images of the composite sheets. The yield stress and modulus of the sheets linearly increased with increasing TEMPO-CNF content up to ~8 vol%. Therefore, we successfully reinforced polyethylene with TEMPO-CNFs using our oven-drying and elastic kneading method.

Effects of Zn Addition into ZSM-5 Zeolite on Dehydrocyclization-Cracking of Soybean Oil Using Hierarchical Zeolite-Al2O3 Composite-Supported Pt/NiMo Sulfided Catalysts.

Zn-exchanged ZSM-5-Al2O3 (ZA) composite-supported Pt/NiMo (NM) sulfided catalysts were prepared using the conventional kneading method and were tested for dehydrocyclization-cracking of soybean oil. The effects of Zn addition on the activity and selectivity of products were investigated under moderate-pressure conditions of 0.5 and 1.0 MPa H2 in the temperature range of 420–580 °C. At the temperature 500 °C and higher, most of the sample soybean oil was converted at both the pressures of 0.5 and 1.0 MPa. At 1.0 MPa and 500 °C, the effects of Zn addition appeared and increased the yields of aromatics, while the catalyst without Zn produced larger amounts of products with more than C18. Further, at 0.5 MPa and 580 °C, the gas formation was inhibited in comparison to the cases of 1.0 MPa and the effects of the Zn addition also appeared and increased the yields of aromatics, while the catalyst without Zn produced larger amounts of products with more than C18. The Pt/NM/Zn(122)ZA test catalyst produced more than 63% of liquid fuels in the range C5–C18, and the yield of aromatics was 13%, the maximum value in the present study. The following reaction routes were proposed. The structure of triglyceride is converted by hydrocracking to three molecules of aliphatic acids and propane on the surface PtNiMo sulfide on Al2O3 support. The converted aliphatic acids are decomposed through decarboxylation to hydrocarbon fragments, which are further decomposed by cracking on the acid sites of the catalyst, the surface of NiMo sulfide, Al2O3, or ZSM-5. Finally, the formed C3 and C4 olefins are transformed to aromatics through the Diels–Alder reaction on the Zn species of ZnZSM-5. On the other hand, although gases were relatively small in amount, aromatic compounds were formed significantly, suggesting that cyclization might directly occur without conversion to gaseous hydrocarbons to some extent.

Preparation of high‐performance carbon nanotube/polyamide composite materials by elastic high‐shear kneading and improvement of properties by induction heating treatment

AbstractPolyamide 66 (PA66) nanocomposites were prepared by compounding carbon nanotubes (CNTs) using an elastic high‐shear kneading method, and the mechanism to understand their excellent properties was verified. In addition, we developed a microwave heat treatment that increases toughness quickly and at low cost. By combining 6.6 vol% or more of CNTs, PA66 with improved mechanical properties, such as higher elastic modulus and yield strength, was achieved, making it possible to obtain a composite having excellent high‐temperature characteristics that does not melt even at a temperature above the melting point. These effects appeared to be due to defibration of CNT aggregates and isolation and dispersion in PA66. A lamellar crystal of PA66 grows around the CNT, forming an interphase. The higher performance appeared to be attributable to a continuous three‐dimensional structure in which CNTs are bound via the interphase, and the improvement of the elastic modulus of the composite material was tentatively ascribed to a Halpin‐Tsai model in which the size of the unit cell of the three‐dimensional structure is introduced. The resulting CNT/PA66 composite materials are superior not only in performance but also in price.

Effect of matrix on aromatics production by cracking and dehydrocyclization of n-pentane using Ga ion-exchanged ZSM-5-alumina composite catalysts

The composite catalysts were prepared from mesoporous alumina as a matrix and Ga-exchanged ZSM-5 as a major catalytic component by the conventional kneading method. The effects of the matrix on the activity and selectivity of aromatics in cracking and dehydrocyclization of n-pentane were investigated. 65-85 wt% of GaZSM-5 was mixed with 0-20 wt% of Al2O3 and 15 wt% of alumina-sol binder. Cracking of n-pentane and successive dehydrocyclization of formed olefins to produce aromatic compounds were performed using a fixed-bed reactor under the conditions, H2 atmosphere and temperature range 450-550 °C. The conversion of n-pentane and the selectivity for aromatics increased with increasing temperature. A catalyst Ga(15)ZSM/10A, where the Ga-exchange ratio was 15%, exhibited the highest conversion among the catalysts with same Ga(15), suggesting that there would be the optimal values of Ga and alumina contents to obtain the high conversion. Further, Ga(15)ZSM/10A exhibited the highest selectivity for aromatics, suggesting that the presence of matrix alumina would appropriately inhibit the cracking to C1 and that the amount of GaZSM-5 would be enough large to increase aromatics to the maximum. Reaction routes and product distributions could be explained by the initial cracking of n-pentane, the small amount of C4 fraction cracking and the successive aromatization through dehydrocyclization of formed olefins.

MgO−SiO2 Catalysts for the Ethanol to Butadiene Reaction: The Effect of Lewis Acid Promoters

AbstractMgO−SiO2 samples, having the composition of natural talc (NT), were obtained by co‐precipitation (CP) and wet kneading (WK) methods. The materials were used as catalysts of the ethanol‐to‐1,3‐butadiene reaction. ZnO, Ga2O3 and In2O3 were tested as promoters. The catalyst WK gave the highest 1,3‐Butadiene (BD) yield among the non‐promoted catalysts because of the high specific surface area and strong basicity. Results suggested that over the neat WK catalyst the acetaldehyde coupling to crotonaldehyde was the rate‐determining process step. Formation of crotyl alcohol intermediate was substantiated to proceed by the hydrogen transfer reaction between crotonaldehyde and ethanol. The crotyl alcohol intermediate becomes dehydrated to BD or, in a disproportionation side reaction, it forms crotonaldehyde and butanol. The promoter was found to increase the surface concentration of the reactant and reaction intermediates, thereby increases the rates of conversion and BD formation. The order of promoting efficiency was Zn>In>Ga.

Studies on spectral characterization and solubility of hydroxypropyl β-cyclodextrin/iloperidone binary and ternary complexes using different auxiliary agents

The antipsychotic drug Iloperidone (ILO) suffers from drawbacks of low solubility and poor bioavailability. In order to overcome such problems, we proposed to prepare binary and ternary complexes using kneading method and further compared for their ability to improve the solubility of ILO. Based on preliminary studies and phase solubility diagram, 1:1 ratio of drug and Hydroxypropyl β-cyclodextrin (HPβCD) was selected. Tartaric acid (TA) and Kolliphor P-188 (KP) were selected as auxiliary agents (AAs) for ternary systems. Significant improvements in the stability constant and complexation efficiency were seen in the phase solubility studies for TA in comparison to KP. Complexation was studied using PXRD, DSC, FT-IR and NMR. Apparent changes in the crystallinity of ILO were observed from PXRD and DSC studies, suggesting formation of complexes. The interactions in the inclusion complexes were confirmed by FT-IR and 1HNMR. Saturation solubility and in vitro dissolution studies showed increase in the drug solubility and release from the complexes compared to the pure drug alone. These studies suggest some interaction between AAs, ILO and HPβCD in ternary complexes. Thus, the present study led to the conclusion that AAs positively enhance solubility of the drug ILO and consequently may improve bioavailability.