Water-insoluble Polymer Research Articles

Formulation Development and Evaluation of Multiple Unit Pellet System of Tamsulosin Hydrochloride

The aim of current work was to grow extended release multiple unit pellets of Tamsulosin Hydrochloride, is an alpha-blocker, used for the healing of the symptoms of a prostate gland condition called BPH (benign prostatic hyperplasia) by extrusion- spheronization (E/S) and solution/suspension layering (S/S) method. In the Extrusion-Spheronization, A ratio of 75:25, 67:33, 64:36 Tamsulosin Hydrochloride and Microcrystalline cellulose were mixed for making drug pellets and extended release (ER) coating was performed in fluidized bed processor (FBP) by solution/suspension layering with Ethyl cellulose (aqueous. dispersion, 4 cps and 7 cps) and Hypromellose (5cps) with different ratios % weight buildups accordingly. In the Solution/suspension layering (S/S) method, Tamsulosin Hydrochloride drug pellets were prepared by layering onto MCC spheres in FBP. These drug pellets were further coated for extended release with HPMC, 5cps and EC, 7cps. In drug coating stage, drug and different binder (Hypromellose, 5 cps) concentrations 8, 10, 12, 14 mg/unit were coated onto the cores for optimization of binder concentration. The weight of MCC spheres were optimized for further formulations. For all the drug coated pellets, ER coating was given with EC, 7cps and HPMC, 5 cps at a coating level of 8% weight by weight. In the extrusion- spheronization (E/S) Optimization of Drug pellets: Among the trials TD3 (Tamsulosin HCl and MCC) showed good mechanical strength with better yield due to increased MCC concentration. Optimization of Extended Release Coating: Optimized TD3 drug pellets were coated with ER coating using water insoluble polymer (Aq.EC 25% dispersion/ EC, 4cps/ EC, 7cps) and water soluble polymer (HPMC, 5cps). Among these polymers, extended release coating was optimized (TD3E14) with the combination of EC, 7cps and HPMC, 5cps at 8% weight build up. In the Solution/Suspension layering: Optimization of binder concentration in drug coating stage: HPMC, 5cps with 12 mg/unit for TF7 was optimized based on %yield. Optimization of MCC spheres in drug coating stage in formulation of ER pellets with different weight drug pellets: The weight of MCC spheres (160, 170, 180, 190 mg/unit) used in the drug coating stage with binder HPMC, 5cps (12 mg/unit). These drug pellets were given with ER coating at 8% weight buildup by using EC, 7cps and HPMC, 5cps. Among these trials, TF7E7 was optimized. Based on the investigations of the present study, conclusions was. formulating low dose, high soluble, BCS class I drug- Tamsulosin Hydrochloride ER formulation by extrusion-spheronization showed flexibility for batch processing and cost effectiveness while solution/suspension layering was process feasible but time consuming due to high drug loading.

Suitability of Ethyl Cellulose As a Binder in Positive Electrode of Aqueous Battery

Novel materials for energy storage devices need to be affordable, durable, safe and environmentally friendly. PVDF, which is the most popular polymer used as a binder in battery cathode electrodes, requires the use of and toxic solvents for processing, such as N-methyl-pyrrolidone (NMP).1 Ethyl cellulose is a biodegradable and water-insoluble polymer. Ethyl cellulose based slurry can be prepared using ethanol as solvent, which makes the process cheaper and more sustainable. Replacing PVDF with more environmentally friendly binder like ethyl cellulose in positive electrode of aqueous battery systems would be beneficial in many ways. It would shorten the assembly procedure due to high speed of solvent evaporation, there are no strict requirements for humidity control and the recycling procedure is easier as there are no fluorinated compounds.2 Therefore, this replacement would enable to produce safer and cheaper energy storage devices.In this work electrodes with different composition have been described using galvanostatic charging-discharging and cyclic voltammetry. LiMn2O4 (LMO) has been used as active material for cathode, carbon black Super P as conductive additive and PDVF or ethyl cellulose as a binder. The electrodes were prepared using different mass ratios of conductive additive and binder to evaluate the performance of this sustainable polymer. Using ethyl cellulose as a binder, discharge capacity 100 mAhg− 1 was achieved at 0.2C rate for LMO cathode which is comparable to the results obtained with PVDF as a binder. 500 cycles at the rate of 1C showed somewhat better capacity retention for electrodes prepared using PVDF. However, the results show that ethyl cellulose is a promising option to replace PVDF as cathode binder in aqueous systems. This binder promising option in the application of aqueous redox flow battery with solid boosters, where large amount of solid charge storage material is used in thanks to increase the capacity of the system.The research was supported by the Estonian Research Council grant PUTJD956 and Magnus Ehrnrooth Foundation.

Isolation of bacteria able to degrade poly-hydroxybutyrate-co-hydroxyhexanoate, and the inhibitory effects of the degradation products on shrimp pathogen Vibrio penaeicida

Poly-hydroxybutyrate-co-hydroxyhexanoate (PHBH) is a biodegradable, water-insoluble polymer produced by specific bacteria. The monomers of PHBH are the hydroxyalkanoic acids 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HH). Previously, we reported that 3HB and 3HH showed marked antibacterial activities against the shrimp pathogenic bacterium Vibrio penaeicida, and that addition of 5% (w/w) PHBH to the standard aquaculture diet significantly increased survival rate in kuruma shrimp (Marsupenaeus japonicus) after challenge by V. penaeicida, which we attributed to the degradation of PHBH to its monomers in the shrimp gut. In the present study, we isolated four strains of bacteria with high PHBH-degrading activity and evaluated their inhibitory effects on V. penaeicida with PHBH: one strain from shrimp gut contents (E1; Pseudoalteromonas shioyasakiensis/P. mariniglutinosa), two strains from coastal surface seawater (F1; P. shioyasakiensis/P. mariniglutinosa, and F5; Alcanivorax dieselolei/A. xenomutans), and one strain that was a contaminant in commercial PHBH powder (Y1; Bacillus pseudofirmus). Strains E1, F1, and Y1 showed strong PHBH-degrading activity within 24 h of inoculation to PHBH-containing agar plates. Although none of the isolates alone had any effect on the growth of V. penaeicida, when cultured with E1 or F1 and PHBH, the growth of V. penaeicida was markedly suppressed. Incubation with E1 and PHBH resulted in a gradual reduction in the concentration of V. penaeicida from 2 days after the start of incubation until the concentration was 1.2% of that in the control (V. penaeicida alone). Incubation with F1 and PHBH resulted in a rapid reduction in the concentration of V. penaeicida from 2 days after the start of incubation until the concentration was only 0.32% of that of the control. Compared with strains E1 and F1, Y1 showed similar PHBH-degrading activity but did not show any suppressive effect on the growth of V. penaeicida until 5 days after the start of incubation. In addition, this suppressive effect was relatively weak compared with that of the other two strains, suggesting that Y1 can quickly degrade PHBH but that it takes several days to produce monomers. Together, these results suggest that addition to the aquaculture diet of PHBH and PHBH-degrading bacteria that rapidly degrade PHBH to its monomers may speed up degradation of PHBH to its monomers in the shrimp gut, and that it would increase resistance to infection mortality by V. penaeicida in kuruma shrimp.

Effect of bound water content on cell adhesion strength to water-insoluble polymers

Adhesion of cells on biomaterials plays an essential role in modulating cellular functions. Although hydration of biomaterials occurs under biological conditions, it is challenging to systematically evaluate the correlation of hydrated water content in biomaterials with the cell adhesion strength. In this report, we investigated the effect of bound water content on the adhesion strength of cells on poly(2-methoxyethyl acrylate) (PMEA) analogue substrates. Water-insoluble PMEA analogues were synthesized to fabricate substrates with a systemically controlled bound water content. To assess the surface properties of their substrates, contact angle measurement, atomic force microscopy (AFM), and fluorescence measurement were conducted. To reflect the effect of bound water of PMEA analogues, the relationship between the bound water content and cell adhesion behavior was evaluated under serum-free condition. From the single cell force spectrometry (SCFS) and microscopic analysis, it revealed that the increment of bound water content on the substrates decreased cell adhesion strength and cell spreading on the substrates. The bound water content exhibited a good correlation with adhesion strength, spreading area, circularity, and aspect ratio of cells. Our findings indicate that the bound water content could contribute to the development of a novel biomaterial and evaluation of cell behaviors on biomaterials. Statement of significanceFor coordinating cell functions, such as growth, mobility, and differentiation, modulating the adhesion strength between cells and their environments is important. Although the hydration to biomaterials has been reported to be closely related to a antifouling property, the effect of hydration water on the cell adhesion behavior is not well understood. We present the first demonstration of essential relationship between cell adhesion strength and hydrated water on a biomaterials surface using the water-insoluble polymers with different hydrated water content. The results reveal that the hydrated water content of polymer substrates strong correlation with adhesion strength of cells. Collectively, the hydrated water content of the biomaterials will be a predominant factor affecting the cell adhesion strength and behavior.

Mechanism of degradation of propargyl alcohol by acid-catalysed hydrolysis and corrosion inhibition efficiency of propargyl alcohol intermediates for carbon steel in hydrochloric acid

Acetylenic alcohols are one of the most important groups of film-forming corrosion inhibitors for carbon steel in hydrochloric acid (HCl). The inhibition mechanism of acetylenic alcohols has been widely discussed for more than 50 years, however, it is not well-understood, particularly with regard to the chemical degradation reactions of acetylenic alcohols in HCl solution. In the present paper, proton nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) techniques were used to investigate the mechanism and the rate of degradation of propargyl alcohol in 3.6–10.8 M HCl at 20–95 °C. Several water-soluble products, such as 1-hydroxypropan-2-one, 2-chloroprop-2-en-1-ol, 2,2-dichloropropan-1-ol and 2-chloropropane-1,2-diol were formed via the electrophilic acid-catalysed addition of HCl and water to the alkyne. Some intermediates further polymerize to form water-insoluble polymers, such as poly (propargyl alcohol), poly (allyl alcohol) and poly (acrolein). The hydrolysis half-life constants of propargyl alcohol decreased with increasing HCl concentration and temperature. The inhibition efficiency (η) of propargyl alcohol and its precursors for carbon steel in 3.6 M and 7.83 M HCl was studied. The critical role of acrolein intermediates on the corrosion performance of propargyl alcohol in hydrochloric acid was identified. Products of propargyl alcohol hydrolysis, 1-hydroxypropan-2-one and 2-chloroprop-2-en-1-ol are poor corrosion inhibitors. However, acrolein and its reactive intermediates are good corrosion inhibitors with inhibitor efficiency, η in the range from 97.69 ± 0.4 % for fresh acrolein to η = 97.94 ± 0.8 % for aged acrolein.

Enzyme Catalyzed Copolymerization of Lignosulfonates for Hydrophobic Coatings.

Enzymatic polymerization of lignin can generate a variety of value-added products concomitantly replacing fossil-based resources. In line with this approach, a laccase from the thermophilic fungus Myceliophthora thermophila (MtL) was used to couple a hydrophobicity enhancing fluorophenol (FP) molecule, namely 4-[4-(trifluoromethyl)phenoxy]phenol (4,4-F3MPP), as a model substrate onto lignosulfonate (LS). During the coupling reaction changes in fluorescence, phenol content, viscosity and molecular weight (size exclusion chromatography; SEC) were monitored. The effects of enzymatic coupling of FP onto LS on hydrophobicity were investigated by the means of water contact angle (WCA) measurement and determination of swelling capacity. Full polymerization of LS resulting in the production of water-insoluble polymers was achieved at a pH of 7 and 33°C. Incorporation of 2% (w/v) of FP led to an increase in WCA by 59.2% while the swelling capacity showed a decrease by 216.8%. Further, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis indicated successful covalent coupling of the FP molecule onto LS by an emerging peak at 1,320 cm–1 in the FTIR spectrum and the evidence of Fluor in the XPS spectrum. This study shows the ability of laccase to mediate the tailoring of LS properties to produce functional polymers.

Cyclodextrin polymers and salts: An Eco-Friendly combination to modulate the removal of sulfamethoxazole from water and its release

This study is aimed to validate water-insoluble cyclodextrin-epichlorohydrin polymer (β-EPI) use to remove, by adsorption, sulfamethoxazole (SMX) from water and then release it via an environmentally friendly treatment so that the adsorbent can be recycled according to one of the objectives of the European Project Life “Clean up” (LIFE 16 ENV/ES/000169).SMX adsorption experiments on β-EPI polymer in-batch were performed, varying different experimental parameters of the process, such as contact time, pH values, and so on.The adsorption process, exothermic and driven by enthalpy, occurs both through the formation of inclusion and association complexes, involves mainly hydrophobic and hydrogen bonds, has a rate-controlling step depending on both pollutant concentration and adsorbent dose and can be described by the Freundlich and Dubinin-Radushkevich models which confirm the polymer surface heterogeneity and the physical nature of the adsorption. The presence of salts gives rise to a general decrease in the SMX sorption, mainly in the case of bromide, which was used to promote the SMX desorption and regenerate the adsorbent. The overall results indicate that β-EPI polymer is not only capable of removing SMX by adsorption with short contact times and a qmax = 10 mg/g but it is also easily regenerated using a 0.5 M solution of sodium bromide without any loss in the adsorption performance and with obvious economic and environmental advantages. The polymer as synthesized, with SMX adsorbed and regenerated was characterized by FT-IR, SEM and DSC.

Formulation and evaluation of bitter taste-masked orally disintegrating tablets of high memantine hydrochloride loaded granules coated with polymer via layering technique

Orally disintegrating tablets (ODTs) improve patient adherence as they can easily disintegrate in the presence of small amount of saliva. However, the bitter taste of the active pharmaceutical ingredient in ODTs reduces patient compliance. The present study aimed to formulate bitter taste-masked ODTs containing high-dose of memantine hydrochloride (MTN) to achieve a balance between bitterness suppression and dissolution rate or disintegration time and mechanical strength. The high MTN-loaded granules were prepared using a fluidized bed granulator. Taste-masking granules coated with the selected polymer were prepared using the layering technique. Three ODTs, composed of granules coated with different polymers, were prepared. The ODT prepared using granules coated with enteric polymers showed the fastest collapse time (>20 s). Dissolution rates of ODTs composed of enteric polymers were reduced by 5 min compared with ODTs composed of non-coated or coated with water-insoluble polymer granules. X-ray computed tomography analysis revealed that low density distribution of ODTs with enteric polymer granules may result in faster disintegration time. Although ODT prepared using enteric polymers had the fastest collapse time, its change in membrane potential caused by adsorption (CPA), corresponding to aftertaste, was the lowest among formulations. This CPA value was lower than the bitterness threshold.

Recyclable palladium based nano-catalytic laborer encaged within bio-granules for dye degradation

Exploitation of water insoluble natural polymers in fabrication of recyclable nano-catalyst is extensively concerned to act as a competitive catalyst for the conventional catalyst. Chitin as water insoluble biopolymer was currently selected to act as biopolymer for anchoring of palladium nanoparticles (Pd NPs@chitin). The affinity of chitin for encaging of Pd NPs was systematically monitored under both of acidic and basic conditions. Under basic conditions, small sized Pd NPs (38.5 nm) were successfully produced with size distribution and surface area of 20 – 59 nm and 20.17 m2/g, respectively. While, in acidic medium, size distribution and surface area were 260 – 885 nm and 8.89 m2/g, respectively. The analysis data approved the mechanism for anchoring of Pd NPs within chitin matrix. The catalytic potentiality of the prepared Pd NPs@chitin as recyclable nano-catalyst was followed up in accelerating the reductive degradation of acidic blue 193. The kinetic studies affirmed that complete reductive degradation of dye was very fast with estimated t1/2 of 1.6 minute and rate constant k1 of 424.9 × 10−3 min−1. After 5 reusing cycles, the catalytic reactivity of the Pd NPs@chitin was slightly decreased and the dye was fully degraded within ca. 15 minute. Excellence in recyclability for the synthesized Pd NPs@chitin approved its compatibility to serve several times for catalysis in degradation of hazards organic pollutants.

Investigation of water-insoluble hydrophobic polyethylenimines as RNAi vehicles in chronic myeloid leukemia therapy.

The discovery of RNA interference (RNAi) more than two decades ago opened avenues for avant-garde cancer treatments that possess the ability to evade issues hampering current chemotherapeutic strategies, owing to its specific gene sequence-driven mechanism of action. A potent short interfering RNA (siRNA) delivery vehicle designed to overcome physiological barriers is imperative for successful RNAi therapy. For this purpose, this study explored the characteristics and therapeutic efficacy of low-molecular weight (MW) polyethylenimine (PEI) with high cholesterol substitution, yielding water-insoluble polymers, in chronic myeloid leukemia (CML) K562 cells. A strong impact of cholesterol grafting on the physicochemical attributes of the resultant polymers and their corresponding complexes with siRNA was observed, with the siRNA binding capacity of polymers increasing and complex dissociation sensitivity decreasing with increase in cholesterol content of the polymers. The modified polymer complexes were significantly smaller in size and possessed higher cationic charge compared to the parent polymer. The interaction with anionic heparan sulfate preoteoglycans present on the cell surface was significant in cellular uptake of the complexes. The therapeutic efficacy of siRNA/polymer complexes was reflected in their ability to effectively silence the reporter green fluorescent protein gene and endogenous CML oncogene BCR-ABL as well as significantly inhibit colony formation by K562 cells post BCR-ABL silencing. The results of this study demonstrated beneficial effects of high levels of hydrophobic substitution on low MW PEI on their functional performance bestowing them the potential to be potent RNAi agents for CML therapy.

Preparation of Solifenacin Succinate Functional Particles Embedded in a Gelling-Swelling Layer (PEGS) and Their Formulation in Orally Disintegrating Tablets.

The purpose of this research was firstly to prepare solifenacin succinate functional particles embedded in a gelling-swelling layer (PEGS) so as to achieve both taste-masking of the unpleasant taste of the drug and rapid drug elution, and secondly to incorporate these PEGS into orally disintegrating tablets (ODTs). In in vitro dissolution tests, initial drug release from the prepared PEGS could be suppressed to less than 1% after 2 min and increased to more than 85% after 30 min by adjusting the composition of the PEGS, in particular the thickness of the outer water-penetration control layer which contains a water-insoluble polymer. For the preparation of ODTs containing PEGS, a semi-direct compression method was adopted in order to prevent damage to the PEGS by processes such as granulation or compaction. The use of a fibre-shaped microcrystalline cellulose with poor fluidity improved the content uniformity of the ODTs, as the crystal fibres became entangled with the PEGS and other additives. The use of spherical mannitol with a hollow structure produced by spray drying imparted relatively high hardness and rapid disintegration properties to the final ODTs containing PEGS, which were tableted using a low compression force. There was no significant difference in the drug-release profiles of the optimally formulated ODTs containing PEGS tableted at different compression forces. The ODTs containing PEGS maintained a drug-release lag time sufficient for taste-masking of solifenacin succinate.

Surface Pressure-Induced Interdiffused Structure Evidenced by Neutron Reflectometry in Cellulose Acetate/Polybutadiene Langmuir Films.

Binary blends of water-insoluble polymers are a versatile strategy to obtain nanostructured films at the air-water interface. However, there are few reported structural studies of such systems in the literature. Depending on the compatibility of the polymers and the role of the air-water interface, one can expect various morphologies. In that context, we probed Langmuir monolayers of cellulose acetate (CA), of deuterated and postoxidized polybutadiene (PBd) and three mixtures of CA/PBd at various concentrations by coupling surface pressure-area isotherms, Brewster angle microscopy (BAM), and neutron reflectometry at the air-water interface to determine their thermodynamic and structural properties. The homogeneity of the films in the vertical direction, averaged laterally over the spatial coherence length of the neutron beam (∼5 μm), was assessed by neutron reflectometry measurements using D2O/H2O subphases contrast-matched to the mixed films. At 5 mN/m, the whole mixed films can be described by a single slightly hydrated thin layer. However, at 15 mN/m, the fit of the reflectivity curves requires a two-layer model consisting of a CA/PBd blend layer in contact with the water, interdiffused with a PBd layer at the interface with air. At intermediate surface pressure (10 mN/m), the determined structure was between those obtained at 5 and 15 mN/m depending on film composition. This PBd enrichment at the air-film interface at high surface pressure, which leads to the PBd depletion in the blend monolayer at the water surface, is attributed to the hydrophobic character of this polymer compared with the predominantly hydrophilic CA.

A Weight-of-the-Evidence Approach for Evaluating, in Lieu of Animal Studies, the Potential of a Novel Polysaccharide Polymer to Produce Lung Overload.

The United States Environmental Protection Agency (EPA) is concerned about the respiratory effects caused by respirable particles of water-insoluble high molecular weight polymers. The EPA has proposed a tiered approach to evaluate polymer lung overload, a kinetic event. Kinetic polymer lung overload in itself is not necessarily adverse, however, inhalation of respirable particulate matter can have adverse effects (i.e., inflammation, fibrosis, etc.). If Tier I testing demonstrates that particles may reach the distal lung (i.e., a non-negligible amount of respirable particles/droplets ≤10 μm in diameter and lack of biosolubility), then animal inhalation testing in Tiers II-IV would be requested. In silico, in chemico, and in vitro alternatives should be considered versus in vivo testing for animal welfare purposes. An in chemico measure of biosolubility was used to demonstrate that a novel α-1,3-glucan polysaccharide, made by enzymatic polymerization of glucose from sucrose, is biosoluble and fits a simple exponential decay model with a half-life on the order of 66 days. The multiple-path particle dosimetry (MPPD) in silico model was used to predict lung burden for the novel α-1,3-glucan polysaccharide. MPPD was validated with measurements in rats exposed to a toner particulate and showed good agreement with lung burden measurements. A simulated 24 month rat exposure yielded 10-20 times less lung burden for the polysaccharide compared to the toner at equivalent exposure concentrations. The MPPD model was refined to include biosolubility data for the polysaccharide polymer. Data for amorphous silica were used to validate the clearance model, and the model incorporating dissolution predicted the amorphous silica lung burden within 20% of measured values. Human equivalent concentrations (HECs) were calculated for each toner rat exposure concentration. HECs were also determined for the polysaccharide at exposure concentrations yielding the same predicted internal doses as the toner. The in vitro, in chemico and in silico studies described here for the novel polysaccharide provide a useful weight of evidence approach in the absence of animal studies for the evaluation of polymer substances where polymer lung overload may be a concern.

Taste Masking of Granulated Acetaminophen by Water Insoluble Ethylcellulose Coating.

Bitter tasting of drugs leads to non-compliance especially in the case of pediatric patients due to their inability to swal-low medication. In this study, we aimed to mask the bitter taste of acetaminophen (APAP) particles through coating. A pH independent water insoluble ethylcellulose polymer was used to coat the APAP. The coating of water insoluble ethylcellulose on APAP can have a significant impact on the dissolution profile. Various grades of APAP were used for coating; fine grade, Compap L90% having wide particle size distribution (PSD), and a special granular (SG) APAP 1680 having narrow PSD. Coating was performed using top spray (Vector) for Compap L90% and SG APAP 1680 grade of APAP. Bitter taste of SG APAP was masked after spraying dispersion equivalent to a weight gain of 10% compared to 35% used for Compap L90%. Using bottom spray (Wurster coater, GPCP 2.0), coating was performed on SG APAP 1680 grade of APAP by spraying aqueous dispersion of ethylcellulose (Surelease) equivalent to a weight gain of 10%. The scalability of the top spray process was also evaluated in GPCG 30 and bitter taste was masked by using Surelease dispersion equivalent to a weight gain of 6%. Coated APAP was examined for particle size (PS), particle size distribution (PSD), flowability, and drug release profile. Dissolution was performed using USP apparatus 2 and 4 in phosphate buffer and evaluated for mechanism of drug release. Particle size obtained for coated SG APAP 1680 via top and bottom spray process was 404 µm d(90) and 487 µm d(90) respectively. The results of the study demonstrated the potential of Surelease dispersion in taste masking. The use of SG APAP 1680 having narrow PSD allowed taste masking to achieve at low weight gain without greatly affecting the dissolution profile.

Effects of the Monomeric Components of Poly-hydroxybutyrate-co-hydroxyhexanoate on the Growth of Vibrio penaeicida In Vitro and on the Survival of Infected Kuruma Shrimp (Marsupenaeus japonicus).

Simple SummaryOutbreaks of bacterial disease in shrimp aquaculture are major causes of economic and production losses. It is, therefore, important to prevent such outbreaks, preferably without the use of antibiotics to avoid encouraging the development of antibiotic-resistant bacterial strains. Several hydroxyalkanoic acids are known to inhibit the growth of pathogenic Vibrio species. Poly-hydroxybutyrate-co-hydroxyhexanoate is a biodegradable, water-insoluble polymer comprising two hydroxyalkanoic acids: 3-hydroxybutyrate and 3-hydroxyhexanoate. Here, we evaluated the inhibitory activities of 3-hydroxybutyrate and 3-hydroxyhexanoate on the growth of the shrimp-pathogenic bacterium Vibrio penaeicida in vitro, and the effect of adding poly-hydroxybutyrate-co-hydroxyhexanoate to the diet on the survival of infected kuruma shrimp (Marsupenaeus japonicus). We found that the activities of 3-hydroxybutyrate and 3-hydroxyhexanoate were pH dependent and that they inhibited bacterial growth at pH close to that found in the shrimp gut (pH 5.9–6.7). Moreover, in shrimp infected with V. penaeicida, survival rates were significantly increased in individuals reared on feed containing poly-hydroxybutyrate-co-hydroxyhexanoate compared with those reared on standard diet, without any negative effects on shrimp growth. These findings suggest that supplementation of standard diet with poly-hydroxybutyrate-co-hydroxyhexanoate could protect aquaculture shrimp from infection by V. penaeicida, which is expected to increase production and reduce overall operational costs.Here, we investigated the inhibitory effects of the biodegradable, water-insoluble polymer poly-hydroxybutyrate-co-hydroxyhexanoate (PHBH) and its two constituent monomers, the hydroxyalkanoic acids 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HH), on the growth of the shrimp-pathogenic bacterium Vibrio penaeicida. In vitro experiments revealed that 3HH showed greater growth inhibitory activity than 3HB against V. penaeicida. In addition, the activities of hydroxyalkanoic acids were pH dependent, being greater at pH 6.0 than at pH 7.0. Investigation of the pH of the shrimp gut revealed a pH range of 5.9–6.7 (mean 6.29 ± SD 0.20), indicating that the physiological environment was suitable for 3HB and 3HH to exert their inhibitory activities against V. penaeicida. In vivo bacterial challenge experiments revealed that survival rates in kuruma shrimp (Marsupenaeus japonicus) infected by V. penaeicida were significantly increased in shrimp reared on feed containing PHBH (0.1%–5% w/w PHBH) compared with that in shrimp reared on standard diet alone. Supplementation with PHBH had no significant effects on three shrimp growth parameters: increase in body weight, daily feeding rate, and feed conversion ratio. These results suggest that supplementation of standard diet with PHBH will increase shrimp resistance to infection by V. penaeicida, thereby increasing shrimp aquaculture productivity.

Solvent-free temperature-facilitated direct extrusion 3D printing for pharmaceuticals

In an era moving towards digital health, 3D printing has successfully proven its applicability in providing personalised medicine through a technology-based approach. Among the different 3D printing techniques, direct extrusion 3D printing has been demonstrated as a promising approach for on demand manufacturing of solid dosage forms. However, it usually requires the use of elevated temperatures and/or the incorporation of an evaporable solvent (usually water). This can implicate the addition of a drying step, which may compromise the integrity of moisture- or temperature-sensitive drugs, and open the door for additional quality control challenges.Here, we demonstrate a new approach that simplifies direct extrusion 3D printing process with the elimination of the post-printing drying step, by merely adding a fatty glyceride, glyceryl monostearate (GMS), to a model drug (theophylline) and permeable water insoluble methacrylate polymers (Eudragit RL and RS). Indeed, rheological studies indicated that the addition of a combination of a plasticiser, (triethyl citrate), and GMS to theophylline: methacrylate polymer blends significantly reduced the extensional viscosity (to <2.5 kPa·Sec) at 90 °C. Interestingly, GMS demonstrated a dual temperature-dependant behaviour by acting both as a plasticiser and a lubricant at printing temperature (90–110 °C), while aiding solidification at room temperature. X-ray powder diffraction indicated incomplete miscibility of GMS within the polymeric matrix at room temperature with the presence of a subtle diffraction peak, at 2(Θ) = 20°. The 3D printed tablets showed acceptable compendial weight and content uniformity as well as sufficient mechanical resistance. In vitro theophylline release from 3D printed tablets was dependant on Eudragit RL:RS ratio.All in all, this work contributes to the efforts of developing a simplified, facile and low-cost 3D printing for small batch manufacturing of bespoke tablets that circumvents the use of high temperature and post-manufacturing drying step.

Preparation of Novel Functional Drug Particles Embedded in a Gelling-Swelling Layer (PEGS) for Taste Masking and Subsequent Rapid Drug Release.

The purpose of this research was to develop novel functional drug particles embedded in a gelling-swelling layer (PEGS) which are capable of achieving both taste-masking of unpalatable drugs and rapid drug elution. The functional particles had a three-layer structure consisting of a core drug layer, a gelling-swelling layer and an outer water-penetration control layer containing a water-insoluble polymer. The concept of formulation design was as follows: when water reaches the gelling-swelling layer, pulverized fine gelling-swelling particles gellate and swell from water absorption to form a rigid layer, thereby preventing drug release. After a defined lag time, the increased volume of the gelling-swelling layer breaks down the outer water-penetration control layer, leading to rapid drug release. In order to adapt this system for use in orally disintegrating tablets, PEGS were prepared at a size of about 250 µm using a fine particle-coating method. Ambroxol hydrochloride was used as a model drug for bitterness and the effects of different gelling-swelling agents and water-insoluble polymers on drug release characteristics from PEGS were examined. In in vitro dissolution tests, it was shown that the drug dissolution rate from PEGS could be suppressed to about 5% after 2 min and increased to more than 85% after 30 min by adjusting the composition and thickness of the outer layer. The PEGS expanded about 1.5-fold and the outer layer was ruptured after 5 min in water.

Water insoluble polymers as efficient binder in fluid bed granulation of metoprolol for preparation hydrophilic matrix extendedrelease tablets

Water insoluble polymers as efficient binder in fluid bed granulation of metoprolol for preparation hydrophilic matrix extendedrelease tablets

Suitability of Ethyl Cellulose As a Binder in Positive Electrode of Aqueous Li-Ion Battery

Novel materials for energy storage devices need to be affordable, durable, safe and environmentally friendly. PVDF, which is the most popular polymer used as a binder in battery cathode electrodes, requires the use of and toxic solvents for processing, such as N-methyl-pyrrolidone (NMP).1 Ethyl cellulose is a biodegradable and water-insoluble polymer. Ethyl cellulose based slurry can be prepared using ethanol as solvent, which makes the process cheaper and more sustainable. Replacing PVDF with more environmentally friendly binder like ethyl cellulose in positive electrode of aqueous Li-ion battery would be beneficial in many ways. It would shorten the assembly procedure due to high speed of solvent evaporation, there are no strict requirements for humidity control and the recycling procedure is easier as there are no fluorinated compounds.2 Therefore, this replacement would enable to produce safer and cheaper energy storage devices.In this work electrodes with different composition have been described using galvanostatic charging-discharging and cyclic voltammetry. LiMn2O4 (LMO) has been used as active material for cathode, carbon black Super P as conductive additive and PDVF or ethyl cellulose as a binder. The electrodes were prepared using different mass ratios of conductive additive and binder to evaluate the performance of this sustainable polymer. Using ethyl cellulose as a binder, discharge capacity 100 mAhg− 1 was achieved at 0.2C rate for LMO cathode which is comparable to the results obtained with PVDF as a binder. 500 cycles at the rate of 1C showed somewhat better capacity retention for electrodes prepared using PVDF. However, the results show that ethyl cellulose is a promising option to replace PVDF as cathode binder in aqueous systems. Further optimization is needed to prepare these novel and sustainable cathodes for aqueous Li-ion battery.The research was supported by the Estonian Research Council grant PUTJD956 and Magnus Ehrnrooth Foundation.

A Review of Starch Biosynthesis in Relation to the Building Block-Backbone Model.

Starch is a water-insoluble polymer of glucose synthesized as discrete granules inside the stroma of plastids in plant cells. Starch reserves provide a source of carbohydrate for immediate growth and development, and act as long term carbon stores in endosperms and seed tissues for growth of the next generation, making starch of huge agricultural importance. The starch granule has a highly complex hierarchical structure arising from the combined actions of a large array of enzymes as well as physicochemical self-assembly mechanisms. Understanding the precise nature of granule architecture, and how both biological and abiotic factors determine this structure is of both fundamental and practical importance. This review outlines current knowledge of granule architecture and the starch biosynthesis pathway in relation to the building block-backbone model of starch structure. We highlight the gaps in our knowledge in relation to our understanding of the structure and synthesis of starch, and argue that the building block-backbone model takes accurate account of both structural and biochemical data.