Preparation of hydrogel capsules with thermoresponsive interpenetrating polymer network using concentric two-fluid nozzles

Hydrogel capsules in which shell was composed of thermoresponsive interpenetrating polymer network (IPN) of crosslinked poly(N-isopropylacrylamide) (PNIAPM) and calcium alginate, were prepared using concentric two-fluid nozzles. To introduce different amount of PNIPAM into the capsule shell, the concentrations of the NIPAM monomer and the polymerization initiator were changed in a wide range and the characteristics of the resulting capsules were evaluated. Spherical and uniformly sized capsules were obtained under all conditions. Elemental analyses showed that the PNIPAM/alginate weight ratio increased with the increase of initial concentrations of NIPAM monomer and polymerization initiator and was proportional to the initial rate of polymerization. In addition, the thermoresponsive properties of IPN hydrogel capsule were measured at temperatures from 10 °C to 50 °C and the thermoresponsive volume change ratio was expressed as a function of the PNIPAM/alginate weight ratio raised to a power. From these results, the relationship between the experimental conditions and the amount of PNIPAM in the capsule shell was clarified, and it indicated the magnitude of volume change of IPN hydrogel capsules can be controlled by introducing the desired amount of PNIPAM in the capsules.     

Development of a Compact-Sized Falling Needle Rheometer for Measurement of Flow Properties of Fresh Human Blood

A compact-sized falling needle rheometer with rapid operation and automatic flow analysis has been developed for viscometry of fresh human blood without anticoagulant. The volume of a fresh blood sample only needs to be 3 mL, and the measuring time is within 2 min after taking a blood sample from the human body. Measured flow properties of human blood are evaluated as a flow curve, that is, the relationship between the shear stress (τ) and shear rate (γ). Observed flow curves of fresh human blood show three typical fluid regions, that is, the Casson fluid region for a low shear rate range of 0 < γ > 140 s^?1, the transition region for a shear rate near 140 s^?1 < γ < 160 s^?1, and the Newtonian fluid region for a high shear rate range of 160 s^?1 < γ > 400 s^?1. Flow properties of human blood such as the yield stress (τ _y) in the Casson fluid region and the apparent viscosity (μ) in the Newtonian fluid region are measured, and they are compared between male and female blood. It is found that the range of human blood viscosity for males is (5.5 to 6.4) mPa · s, and for females is (4.5 to 5.3) mPa · s. The viscosities of male blood without anticoagulant show higher values than those of female blood. Human blood viscosities with anticoagulant show a lower value than that without anticoagulant. A linear relationship between the hematocrit value, that is, the volume percentage of red corpuscles in the human blood, and the apparent viscosity are observed for both male and female blood. This article is concerned with the flow analysis of fresh human blood viscosity without anticoagulant using a newly developed compact-sized falling needle rheometer.     

A novel capsule-based smell test fabricated via coaxial dripping

In this paper, we demonstrate that aromatic oil capsules, produced by dripping droplets, can offer a simple, yet effective, testing tool to aid in the diagnosis of various diseases, in which the loss of smell is a key symptom. These include chronic neurological conditions such as Parkinson''s and Alzheimer''s diseases, and acute respiratory infections such as that caused by COVID-19. The capsules were fabricated by concentrically dripping oil/alginate droplets, from a coaxial nozzle, into an oppositely charged ionic liquid. This fabrication technique enables full control over the capsule size, the shell thickness and the volume of the encapsulated oil. After formation, liquid capsules were left to dry and form a solid crust surrounding the oil. The prototype test consists of placing a standardized number of capsules between adhesive strips that users crush and pull apart to release the smell. In addition to the fabrication method, a simple mathematical model was developed to predict the volume of encapsulated oil within the capsule in terms of the flow rate ratio and the nozzle size. Tensile tests show that capsule strength is inversely proportional to its size owing to an increase in the shell thickness. By increasing the alginate concentration, the load required to rupture the capsule increases, to the point where capsules are too stiff to be broken by a fingertip grip. Results from a preliminary screening test, within a group of patients with Parkinson''s disease, found that smells were detectable using a ‘forced choice’ paradigm.     

Reproductive accuracy of safety valve two-phase mass flow capacity models in case of air/water, resp., viscous liquid flow duty

On the basis of integral statistical key figures, the reproductive quality of the Extended Maximum Disequilibrium Method as proposed by Wieczorek [?] is in the range of the liquid phase viscosity of up to 2800 mPa?s in comparison with that exhibited by the models according to ISO/CD 4126-10 [?], Lenzing [?], Leung [?], Gosslau and Weyl [?], resp., Fauske [?] higher and in parallel so far unique to achieve under all conditions an oversizing of the relief area. This result is partially offset by a comparatively higher average uncertainty, resp., larger relief area oversizing in the range of viscosities of up to 100 mPa?s. The apportionment of the integral statistical figures as a function of the stagnation air mass quality shows that most of the methods – independently of the liquid viscosity level – feature the largest deviations, resp., oversizing in the range of mass flow qualities between 0.1 and 1%. This is unfortunately just the discharge mass flow quality used in sizing in case of partially liquid loaded reactor top venting.     

Preparation of alginate-gelatin capsules and its properties

Capsules based on alginate and gelatin prepared by extrusion method could increase the cell numbers of Lactobacillus casei ATCC 393 to be 10⁸ CFU·g⁻¹ in the wet state of the capsules. The capsules were spherical, smooth-surfaced and non-aggregated with a diameter of (4.0 ± 0.3) mm. The behavior of the samples were quite similar at low relative humidity (33%, 52%) and the ratio of weight change reached 93%. Four kinds of capsules in simulated gastric fluid (SGF) exhibited shrinkage while the beads eroded accompanied with slight swelling in simulated intestinal fluid (SIF). The pH values affected the stability of the capsules and with the increase in pH, the capsules changed from shrank then swelled and finally, broke into pieces. The capsules behaved differently under different ion intensities and the introduction of gelatin weakened the stability of capsules compared with the alginate ones. Cells of L. casei ATCC 393 could be continuously released from the capsules in the simulated gastrointestinal tract (GIT) and the release amounts and speeds in SIF were much higher and faster than those in SGF.     

Rheology and Filling Characteristics of Particulate Dispersions in Polymer Melt Formulations for Liquid Fill Hard Gelatin Capsules

Abstract

The rheology and capsule filling properties of molten excipients, Dynafill, Dynasan-114, Lutrol-F68, and polyethylene glycols (PEG) 6000, 8000, 10,000, and 20,000 have been investigated. Lactose (α-monohydrate) was selected as a model particulate solid with low solubility in PEG in order to investigate the effects of disperse phase particle size, concentration, and PEG molecular weight on rheology and capsule filling properties of these systems. All excipients behaved as Newtonian fluids between 65 and 90°C, which was chosen as a possible temperature range for liquid filling of hard gelatin capsules. The excipients, apart from Dynasan-114 and PEG 20,000, showed satisfactory capsule filling properties at 70°C using a semiautomatic filling machine. Dynasan-114 (viscosity = 0.012 Pass at 70°C) leaked from the seals between the hopper and pump of the filling machine, whereas PEG 20,000 (viscosity = 24 Pas at 70?C) showed bridging of the molten polymer between successive capsule bodies during the filling process. The effect of disperse phase (lactose) particle size and concentration, and continuous phase (PEG) molecular weight on the apparent viscosity and filling properties of the non-Newtonian dispersions were investigated at 70°C. Satisfactory filling of the dispersions was achieved at 70°C up to a limiting concentration of disperse phase which was dependent upon disperse phase particle size and continuous phase molecular weight, and corresponded to a pronounced increase in apparent viscosity of the dispersion.     

Mechanistic Study on Hydration and Drug Release Behavior of Sodium Alginate Compacts

ABSTRACT

The influence of sodium alginate viscosity on the dynamics of matrix hydration, solvent front movement, swelling, erosion, and drug release from alginate matrix tablets were examined. The solvent front showed preferential penetration from the radial direction even though matrix swelling showed axial predominance. This study proposed alternative views for the anisotropic behavior of hydrating alginate compacts, namely, formation of gel barrier with different permeability characteristics, tension at the gel-core interface and preferential radial erosion, in addition to an in-depth examination on the contribution of stress relaxation of hydrated polymer as well as core expansion. Alginate matrices demonstrated pH-dependent hydration, swelling and erosion behavior, resulting in pH-dependent drug release mechanisms. Dissolution profiles for alginate matrices of different viscosities were similar in acid but differed upon increase of pH. This was due to the influence of alginate viscosity grade on liquid uptake, erosion and pronounced swelling at near neutral pH.     

Poloxamer 407 as a Thermogelling and Adhesive Polymer for Rectal Administration of Short-Chain Fatty Acids

Objectives: The purpose of the study was to gel a rectal solution of short-chain fatty acids to decrease the loss of active materials in the colonic lumen and thereby optimize their absorption. Methods: Five thermogels were prepared with poloxamer 407 at concentrations ranging from 17% to 20%. Their viscosities were measured at room temperature and 37°C, and their gelling temperatures were determined. The adhesive properties of each gel were assessed in vitro at 37°C. Short-chain fatty acid release was studied using Guyot cells. Results: From the threshold concentration of 17.5%, the solutions, Newtonian at room temperature (50–80 mPa · s), gelled at 37°C. The higher the concentration, the higher the viscosity (1750 to 49,000 mPa · s), the lower the gelling temperature (27.6°C to 23.4°C), and the stronger the work of adhesion (2.2 to 4.5 mJ). Short-chain fatty acid release from the 18% polymer gel was decreased by 60% compared to the rectal solution. Conclusion: The 18% poloxamer 407 concentration provided a solution that was liquid at room temperature, that gelled at 37°C, possessed adhesive properties, and controlled short-chain fatty acid release.     

Exploratory Characterization of a Perfluoropolyether Oil as a Possible Viscosity Standard at Deepwater Production Conditions of 533 K and 241 MPa

DuPont’s perfluoropolyether oil Krytox $^{\textregistered }$ GPL 102 is a promising candidate for the high-temperature, high-pressure Deepwater viscosity standard (DVS). The preferred DVS is a thermally stable liquid that exhibits a viscosity of roughly 20  $\hbox {mPa} \cdot \hbox {s}$ at 533 K and 241 MPa; a viscosity value representative of light oils found in ultra-deep formations beneath the deep waters of the Gulf of Mexico. A windowed rolling-ball viscometer designed by our team is used to determine the Krytox $^{\textregistered }$ GPL 102 viscosity at pressures to 245 MPa and temperatures of 311 K, 372 K, and 533 K. At 533 K and 243 MPa, the Krytox $^{\textregistered }$ GPL 102 viscosity is $(27.2 \pm 1.3)\,\hbox {mPa} \cdot \hbox {s}$ . The rolling-ball viscometer viscosity results for Krytox $^{\textregistered }$ GPL 102 are correlated with an empirical 10-parameter surface fitting function that yields an MAPD of 3.9 %. A Couette rheometer is also used to measure the Krytox $^{\textregistered }$ GPL 102 viscosity, yielding a value of $(26.2 \pm 1)\,\hbox {mPa} \cdot \hbox {s}$ at 533 K and 241 MPa. The results of this exploratory study suggest that Krytox $^{\textregistered }\, \hbox {GPL}$ 102 is a promising candidate for the DVS, primarily because this fluoroether oil is thermally stable and exhibits a viscosity closer to the targeted value of 20 mPa $\cdot $ s at 533 K and 241 MPa than any other fluid reported to date. Nonetheless, further studies must be conducted by other researcher groups using various types of viscometers and rheometers on samples of Krytox GPL $^{\textregistered }$ 102 from the same lot to further establish the properties of Krytox GPL $^{\textregistered }$ 102.     

A study of cooling rate of the supercooled water inside of cylindrical capsules

An experimental apparatus was developed to investigate the supercooling phenomenon of pure water inside cylindrical capsules used for cold storage process. The Phase Change Material (PCM) used was distilled water. The external coolant material was a water–alcohol mixture (50% vol.), controlled by a constant temperature bath (CTB) in four fixed values (?4 °C, ?6 °C, ?8 °C, and ?10 °C). Temperatures varying with time were measured inside and outside the capsule. Cylindrical capsules with internal diameter of 30 mm, 45 mm, and 80 mm, with 1.5 mm wall thickness were made in aluminum, bronze or acrylic materials. The Cooling Rate (CR) was investigated for different positions on the internal wall of the capsule, for different external coolant temperatures (T_c), different capsules diameters and different materials. The results showed that the cooling rate is a strong function of the angular position on the internal wall, the coolant temperature, the capsule material, and the capsule's diameter.     

Novel alginate coated hydrophobically modified chitosan polyelectrolyte complex for the delivery of BSA

Polysaccharides based polyelectrolyte complex nanoparticles (PCNs) intended for use in the delivery of macromolecules were prepared by the self-assembly of deoxycholic acid hydrophobically modified chitosan (CS-DCA) core and then coated with sodium alginate (ALG) shell. The CS-DCA capable of forming nano-sized self-aggregates in medium was prepared by the grafting of DCA to CS. In order to increase the stability of nanoparticles and prevent burst release of drug in bloodstream, polyanionic ALG was coated on the surface of positively charged CS-DCA nanoparticles to form PCNs. Dynamic light scattering results revealed that the mean diameter of the PCNs was about 330 nm, larger than that of uncoated nanoparticles (~150 nm). The zeta potential was big enough to keep the stability of PCNs (?28 mV); no size change was found even upon 1 month storage. Bovine serum albumin could be easily incorporated into the PCNs with encapsulation efficiency (>44 %) and keep a sustained manner without burst release when exposed to PBS (pH 7.4) at 37 °C. These results suggested that PCNs may be a promising drug carrier for a prolonged and sustained delivery in the bloodstream.     

Morphological Study of Cavity and Worthington Jet Formations for Newtonian and Non-Newtonian Liquids

In this article a morphological study of the cavity formation and the liquid column formation of the Worthington jet with lapse of time for the Newtonian liquids of water and glycerine wt 70% solution and for non-Newtonian liquids of acrylic copolymer solution of ACA-wt1%, ACA-wt2%, and ACA-wt3% by a droplet falling to the free surface of the target liquid in the cylindrical container from a height of H = 100, 200, 300, 400, and 500 mm is described. The calculated results by the energy equation for the maximum cavity radius Rmax/d and for the morphological size D · h/d² of the Worthington jet are in agreement with the experimental results. In order to take photographs of the cavity formation and the Worthington jet formation with lapse of time, a CCD camera was used. The falling droplet and the target liquid are the same material. Here d is the mean diameter of the droplet and D and h are the mean diameter and maximum height of the liquid column of the Worthington jet.     

DETERMINATION OF TIME-DEPENDENT CONSTITUTIVE MODEL PARAMETERS FOR MICROCRYSTALLINE CELLULOSE

ABSTRACT

Material parameters of a time-dependent elasto-viscoplaslic constitutive model, proposed by Adachi and Oka, have been determined for microcrystalline cellulose. Adachi and Oka model has eight material parameters, with five of them (i.e., consolidation index, swelling index, critical index, shear modulus, and Poisson's ratio) same as those in the more commonly used in time-independent modified Cam-clay model, and remaining three parameters account for time-dependency. To measure the time-dependent parameters, constant strain-rate conventional triaxial compression (CTC) test was designed and conducted using Penn Slate's flexible-boundary cubical triaxial tester (CTT) with microcrystalline cellulose as the test material. To deposit the powder, the sprinkle filling method was used in a layer by layer fashion with a small spoon. The three time-dependent Adachi and Oka parameters were determined from these tests. Adachi and Oka model was verified by comparing the predicted values from the model with measured values from the CTT at 0.05 level of significance. Results showed that: 1) there were no significant differences (p > 0.05) between measured and predicted HTC responses at all loading rates; 2) failure values were predicted accurately (p > 0.05); and 3) there were significant differences (p < 0.05) between measured and predicted CTC responses at all loading rates.     

Chitosan and alginate polyelectrolyte complex membranes and their properties for wound dressing application

This study investigated the characteristics and drug release properties of membranes of chitosan and alginate prepared via a casting/solvent evaporation technique. Membranes of chitosan and alginate with silver sulfadiazine as model drug incorporated in different concentrations and different membrane compositions were obtained. The polyblend solution viscosity reached to the highest at the composition polyblends of (1:1). This chitosan/alginate membranes showed pH- and ionic strength-dependent water uptake properties and had the WVTR rang from 442 to 618 g/m²/day. The maximum value of the dry membrane of breaking strength was 52.16 MPa and the maximum value of the wet membrane breaking elongation was 46.28%. The results of controlled release studies showed that the silver sulfadiazine release rate was the fastest when the alginate content was 50%. On the basis of the requisite physical properties, the chitosan–alginate PEC membrane can be considered for potential wound dressing or controlled release application.     

基于Faster R-CNN改进的数粒机系统

目的解决目前数粒机只能计数不能同时分拣残损药粒的问题。方法设计以Faster R-CNN深度神经网络为核心的药粒数粒机系统。在原有的数粒机基础之上,更换CCD线阵相机为面阵相机,以满足图像采集的需求,进一步使用图像分割和多线程技术加快图像处理速度。最终通过训练好的Faster R-CNN网络检测出目标并分拣。结果经过测试集的验证,正常药粒识别率达到了95.47%,残损药粒识别率达到了97.94%,单幅图像处理达到了65 ms的实时速度。结论该方法在传统的计数基础上很好地融合了先进的深度学习技术,实现了目标的自动分拣。     

Liquefied Capsules Coated with Multilayered Polyelectrolyte Films for Cell Immobilization

Natural‐derived polymers are used to coat liquid‐core capsules layer by layer to encapsulate cells. Human osteoblast‐like cells (SaOs‐2) are encapsulated in such spherical devices using a three‐step methodology: i) ionotropic gelation to produce alginate beads encapsulating the cells; ii) layer‐by‐layer coating using water‐soluble chitosan and alginate; and iii) core liquefaction. Cells remain viable for 3 d after the encapsulation procedure, suggesting that the developed capsules possess a semipermeable, nanostructured coating. All of the capsules exhibit a spherical shape, smooth surface and liquid‐core characteristics. All of the processes are conducted under mild conditions and physiological pH. We consider that the methodology employed in the development of the capsules obtained from natural‐based biomaterials has potential to find applicability in the development of scaffolds or cell carriers in tissue engineering and regenerative medicine.     

ICF靶丸表面形貌及球度误差检测

为了对ICF靶丸的表面形貌及球度误差进行高精度测量,开发了一台五轴坐标测量机,并采用锥光全息技术的激光测头实现对靶丸表面的高精度、非接触检测。首先,根据靶丸表面的结构特点,改进了基于最小二乘的球度误差评价算法;然后,介绍了作为实验平台的五轴坐标测量机的整体配置,推导了该坐标测量机的测量数学模型,该坐标测量机可实现在多个姿态下对靶丸的非接触取点测量;最后,在相同条件下,进行了5次实验测量,其结果表明:靶丸球度误差测量的均值为0.0021 mm,标准差为2.07 x10^-4 mm。该检测方法可以满足对靶丸表面形貌及球度误差高精度、高稳定性的测量要求。     

不同分散剂中碳纳米管的定向操控技术

利用介电电泳可以实现悬浮液中碳纳米管的定向操控．碳纳米管可以用表面活性剂和有机溶剂进行分散．对比了表面活性剂（十二烷基苯磺酸钠,黏滞系数为1.312mPa·s）和有机溶剂（二甲基甲酰胺,黏滞系数为0．802mPa·s）,发现表面活性剂悬浮液中碳纳米管的溶解和分散效果好于有机溶剂中的溶解和分散效果,能实现单根分散．根据介电电泳原理,悬浮液中的碳纳米管在外加电场诱导下产生极化从而被驱动;分析了表面活性剂悬浮液和有机溶剂中碳纳米管的定向效果,发现有机溶剂中碳纳米管的定向效果好于表面活性剂悬浮液中的效果,表面活性剂悬浮液的黏滞系数大是阻碍外加电场有效定向操控碳纳米管的原因．     

Powdered self-emulsified lipid formulations of meloxicam as solid dosage forms for oral administration

The objectives of this study were to prepare a powdered self-emulsified (SEDDS) formulation of meloxicam and to compare its oral bioavailability against commercial Mobic^® tablets. The SEDDS formulation was prepared by in situ salt formation of meloxicam in a blend of lipid excipients and aqueous tris (hydroxymethyl) aminomethane solution. The liquid SEDDS was subsequently adsorbed on silica powder and was tested for size, flow, and crystal growth. The flowability index of the powdered SEDDS was borderline acceptable. Absence of crystal growth with storage was confirmed by DSC and PXRD studies. Dissolution of meloxicam from the powdered SEDDS was >90% vs. <12% for powdered meloxicam and <80% for the commercial tablets. Stability of the powdered formulations after storage in gelatin and HPMC capsules was also evaluated to study the effect of water migration from the fill into capsule shells. Capsules softened to a different extent as a function of fill material with HPMC capsules showing greater resistance to water migration. Finally, oral bioavailability of the formulations was evaluated in beagle dogs. Powdered meloxicam SEDDS formulation showed a 1.3-fold increase in AUC vs. commercial Mobic^® tablets. Overall, this study described a novel SEDDS formulation of meloxicam and outlined a systematic approach to adsorbing and testing the flow and stability behavior of powdered SEDDS formulations.     

Novel electrohydrodynamic preparation of porous chitosan particles for drug delivery

Uniform spherical chitosan particles of size <10 μm in diameter are important in drug delivery applications due to their excellent biocompability and biodegradability. A high concentration of chitosan in the particles can help to control the release of drugs and methods for processing high viscosity chitosan solutions are therefore required. In principle, any type of polymer, whether hydrophobic or hydrophilic, can be electrosprayed to obtain monodisperse particles of diameter <10 μm. In practice, however, electrospraying of biopolymers having viscosities of >100 mPa s results in particles >10 μm diameter. In this study, by reducing surface tension of a high viscosity chitosan suspension, it was found that smaller diameter particles could be prepared. Chitosan solutions were electrosprayed in the stable cone-jet mode to systematically study the relationship between particle diameter, viscosity and surface tension. Increasing viscosity resulted in larger diameter particles with a broad size distribution, but decreasing surface tension had the opposite effect. Results show that a chitosan solution having a viscosity of ~80 mPa s can be used to prepare chitosan particles of diameter ~2.5 μm which on drying reduced to particles of 500 nm.