Aqueous-based Solvents Research Articles

Development of Enteric Diclofenac Sodium Microparticles Through a Spray-Drying Process Facilitated by Different Aqueous Dispersion Systems

The objective of this study was to prepare enteric diclofenac sodium microparticles using an aqueous dispersion system via spray-drying. Two aqueous-based solvent systems, phosphate buffer at pH 7.0 and ammonium hydrogen carbonate solution, were employed as the feed dispersion media in the spray-drying process based on the solubility characteristics of Eudragit® L100. At a drug-to-polymer ratio of 1:1, the optimal solids concentration in the feed dispersion was determined to be 2% w/v, as it enabled an approximately 5-30 µm smooth-surfaced spherical microparticle with a high production yield. Diclofenac sodium was efficiently encapsulated within the microparticles, existing as solid dispersion in a partially amorphous form. Notably, the spray-drying conditions utilized in this study obviated the need for further heating for microparticles prepared using ammonium hydrogen carbonate solution, as the residual ammonium could be completely eliminated during the spray-drying process. The two-stage biorelevant drug release profile of enteric microparticles demonstrated their ability to inhibit drug dissolution under acidic conditions while facilitating drug release under basic conditions. The phosphate buffer-based microparticles exhibited greater protection efficiency under acidic conditions compared to ammonium hydrogen carbonate-based systems, despite residual alkaline salt being present in the microparticles. These results validate the potential of the developed microparticles for use as an enteric drug delivery system.

Evaluation of the Physicochemical and Micromeritic Properties of Exudate Gum of Cussonia arborea Stem Bark in Conventional Tablet Formulation

Pharmaceutical excipients are classified based on the function(s) in the processing and/or finished product. However, functionality evaluations, procedures, and related acceptance criteria for excipients tend to depend on the dosage form, and assessment is usually done on a case-by-case basis. This means that any useful and reliable evaluation of the overall functionality-related properties is only possible within the context of the specific formulation method. This study evaluated the physicochemical, functional, and related properties of purified gum obtained from the stem bark of the Cussonia arborea tree. The purified gum was acidic (pH 5.32–5.50) with percentage (%) moisture content and insoluble matter of 13.33 ± 0.33 and 0.47 ± 0.01, respectively. Moreover, it was soluble in all the aqueous-based solvents but insoluble in all the organic solvents. The total ash of the gum was higher than that of international standard gum Arabic. Micromeritic properties indicated the need for a flow aid to improve flowability. Six formulated batches of tablets containing 0.5–5%w/w of gum, respectively, were generally soft with none passing the USP T80 standard of drug dissolution indicating poor tablet binding and drug-releasing properties. The disintegration action of CAPG was poor (only batches containing 0.5 and 1% CAPG passed) and was not comparable to that of the standard corn starch. The gum was therefore considered a poor disintegrant and binder in the formulation of conventional release tablets.

Reduced Toxicity and Aqueous-Based Solvent Using Phosphoric Acid as the Dopant Source for Formation Emitter Layer of Silicon Solar Cells

Reduced Toxicity and Aqueous-Based Solvent Using Phosphoric Acid as the Dopant Source for Formation Emitter Layer of Silicon Solar Cells

Physicochemical and Microbiological Characteristics of Stem Bark Exudate Gum of Cordia millenii Tree in Conventional Release Tablets.

The development of a raw material into an acceptable pharmaceutical excipient involves evaluation of the physicochemical and formulation properties of the potential raw material. Results from these evaluations may serve as a guide to subsequent use of the substance. The objective of the study was to evaluate the physicochemical and microbiological properties of the stem bark gum of Cordia millenii tree in conventional release paracetamol tablets. From the physicochemical evaluations, the gum was slightly acidic and soluble in all the aqueous-based solvents, except 0.1 N HCl in which it was sparingly soluble. All the absorptive properties of the gum indicated tablet disintegrating potential for tablet formulation. The total ash of the gum was higher than that of the international standard gum arabic. Micromeritic properties of the gum indicated the need for a flow aid to improve its flowability. There were no harmful microorganisms detected in the gum. Aerobic organisms and moulds and yeast were detected within permissible limits. Tablets formulated using six different concentrations of gum dispersions as a binder were generally soft and failed the USP T80 standard of dissolution, indicating poor binding and drug releasing properties. Quality control properties of three different batches of tablets containing varying concentrations of the dry gum as a disintegrating agent were comparable to tablets containing equal concentrations of corn starch. The in vitro drug releases were similar at all-time points of drug evaluation. The gum can therefore be considered as a good disintegrant in the formulation of conventional release tablets.

Conversion of gaseous effluents of power plant to sodium carbonate: A value-added material for powder detergent

The CO 2 emission from thermal power plants is one of the major causes of Global warming. Various CO 2 capture technologies such as chemical absorption and adsorption, solvent scrubbing, and membrane processes have been proposed; however, these approaches are expensive and energy-intensive. Here, we have developed a new process for the conversion of gaseous effluents from thermal power plants into nanostructured materials without producing secondary waste. The process includes passing the gaseous industrial effluent (flue gas) in three different aqueous-based solvents (neutral, acidic and alkaline). After completing the reaction, the alkaline solvent was evaporated to get a solid mass. A powder X-ray diffraction study confirms the formation of sodium carbonate. Transmission electron microscopic studies show the formation of a spherical particle of size ~150 nm. Further, gas absorption study reveals high absorption of CO 2 . The as-obtained sodium carbonate was used for the detergent formulation. The result shows grade I detergent has been prepared with improved detergency power (> 65%), having less than 15% active alkalinity, ~19% active ingredient and less than 1% ash. The above work shows a new approach for the scientific as well as the industrial community to convert pollutants into useful products. Design of new process for conversion of power plant effluent into cleaning productKeywords • Flue gas generated from the coal power plant has been captured • Treatment of captured flue gas has been done for the conversion into valuable sodium carbonate • Extracted sodium carbonate has been used for making powder detergent • No by-product has been obtained at the end of conversion

Selection of hydrotropes for enhancing the solubility of artemisinin in aqueous solutions

Artemisinin is an antimalarial substance very sparingly soluble in water. In the attempt to identify environmental-friendly and non-toxic aqueous-based solvents to extract it from Artemisia annua L., the solubility of artemisinin in aqueous solutions of different hydrotropes was measured at 303.2 K, for hydrotrope concentrations up to 5 M. The ability of the studied hydrotropes for enhancing the artemisinin solubility increases in the following order: Na[N(CN)2] < Na[SCN] < [Chol][Van] < [Chol][Gal] < [N4,4,4,4]Cl < [Chol][Sal] < [P4,4,4,4]Cl < Na[Sal], with Na[Sal] allowing an increase in the solubility of 750 fold compared to pure water.The COSMO-RS model and experimental Kamlet-Taft solvatochromic parameters were applied to connect the solubility enhancement with solvent properties. At low hydrotrope concentration, the solubility increases with the decreasing of the difference between the Apolar Factors of the hydrotrope and artemisinin, while for higher hydrotrope concentration, the hydrogen-bond acceptor character of the hydrotrope seems to have an impact on the solubility enhancement. Even if some mechanistic understanding is still to unfold, quantitatively the empirical correlations of solubility enhancement with the hydrotrope concentration and the solvatochromic parameters show very high accuracy. In particular, 93% of the change on the artemisinin solubility enhancement could be explained using the hydrotrope concentration and two combined solvatochromic parameters (αβ and π*2) as explaining variables.

Silica Bonded Bis(Hydrogensulphato)Benzene as a New, Sustainable Catalytic Material for an Efficient and Aqueous Based Synthesis of 5-Oxo-4H-Pyrano[3,2-c]Quinolone Scaffolds

Catalytic use of benzene-1,3-disulfonic acid at an ordinary condition gets restricted due to its high hygroscopic and moisture sensitive nature. In the present study, a new catalytic material silica bonded bis(hydrogensulphato)benzene (SiO2-BHSB) was synthesized through a sequence of reactions, where the active catalytic part benzene-1,3-disulfonic acid was grafted on the surface of micro-sized silica by the chemical bonding. Structural features, purity, thermal stability, and acid strength of the synthesized SiO2-BHSB material were confirmed by the adequate analytical techniques such as FT-IR, solid-state CP-MAS 13C-NMR, CP-MAS 29Si-NMR, EDX, DTG, TGA, and volumetric studies. The synthesized material SiO2-BHSB was observed as an efficient and sustainable reaction promoter for a tandem reaction between 4-hydroxy-1-methyl-2(1H)-quinolone, malononitrile, and structurally diverse aldehydes to offer pyrano[3,2-c]quinolone scaffolds. An environmentally benign catalytic protocol in aqueous based solvent and at ordinary energy conditions was developed, wherein a tiny amount (3 mol%) of SiO2-BHSB was observed sufficient to catalyze the synthesis pyrano[3,2-c]quinolone scaffolds. Structures of the synthesized pyrano[3,2-c]quinolone derivatives were established from their physical and spectrometric data. Catalyst recovery and reuse study revealed that SiO2-BHSB sustains its catalytic activity even after five runs of its reuse. Use of aqueous-based solvent, environmentally compatible reaction conditions, ease of catalyst recovery and reuse are the additional salient features of the present protocol.

Developing a cloud point extraction process for lipopeptide recovery from cell-free broth of Bacillus sp. GY19

ABSTRACT Biosurfactants can be potentially used in food, cosmetics, pharmaceuticals, and environmental remediation because of their biodegradability and low toxicity. However, it is very challenging to recover biosurfactants from fermented broth as they are temperature-sensitive and present at dilute concentrations. This study aims to develop an alternative process that uses cloud point extraction (CPE) to recover lipopeptides biosurfactant from cell-free broth of Bacillus sp. GY19. The nonionic surfactant, Triton X-100, was selected as the aqueous-based solvent for CPE. Under the optimal conditions lipopeptides concentration in Triton X-100 was 23,000 mg/L, which is 14.8-folds higher than that in cell-free broth. Lipopeptides and Triton X-100 exerted a positive synergistic effect in reducing the critical micelle concentration of mixed micelles with a β value of −1.9. This could be considered a co-benefit of using CPE for biosurfactant recovery. Two techniques for back extraction of lipopeptides after the CPE process were proposed. Silica gel 60 selectively adsorbed Triton X-100 with 44% removal, while maintaining lipopeptides recovery at 86%. Cold acetone precipitation could remove 99% of Triton X-100 by precipitating lipopeptides. However, a 1%(w/v) SDS solution had to be used to re-solubilize the dehydrated lipopeptide

Separation of proanthocyanidin from red sorghum seed extract using macroporous resin

Proanthocyanidin has been extracted from red sorghum seed with Ultrasound-Assisted Extraction using an aqueous-based solvent. Proanthocyanidin concentration in the extract is relatively low mixing with other compounds. The adsorption method was chosen to separate proanthocyanidin compounds due to the relatively simple operation to recover targeted solutes from low concentration solutions. The purpose of this study was to find an efficient adsorbent for separating proanthocyanidin from red sorghum seed extract. Two types of macropore resin were investigated, namely macropore resin AB-8 and D101. Besides the slight difference in average pores diameter, D101 is non-polar while AB-08 is weak polar resin. The initial concentration of proanthocyanidin compounds in the extract was 0.872 mg/ml. Adsorption processes were performed to reach equilibrium. AB-8 and D101 macropore resins showed adsorption capacity of 34.65 mg/g and 30.36 mg/g with the percent recovery of 79.64% and 69.79%, respectively. Macropore resin AB-8 offers a higher adsorption capacity than macropore resin D101. Additionally, adsorption with AB-8 could reach equilibrium after 24 hours, while D101 took significantly longer to reach equilibrium after 48 hours. While both AB-8 and D101 macropore resins demonstrated reasonable performance as potential adsorbents for recovering proanthocyanidin from red sorghum extract, AB-8 showed better performance in terms of capacity and adsorption rate.

Silica Chemisorbed Bis(Hydrogensulphato)Benzene (SiO2-BHSB) as a New, Environmentally Benign and Recyclable Catalyst for an Efficient Synthesis of Biscoumarin Scaffolds in Water Based Solvent

The immobilization of homogeneous catalytic material over the inert heterogeneous support is a recent strategy to overcome the drawbacks and unite the merits associated with the homogeneous as well as heterogeneous catalysts. However the physisorption-induced immobilization does not serve the purpose because of its sensitive reversible nature, a tiny change in reaction parameters may revert the physisorption and so the immobilization. In this work, a new catalytic material silica chemisorbed bis(hydrogensulphato)benzene (SiO2-BHSB) was achieved through the chemisorption of bis(hydrogensulphato)benzene as an active catalytic part on the surface of porous silica. Structural features, purity, thermal stability, and acid strength of the synthesized SiO2-BHSB material were established by adequate analytical techniques, such as FT-IR, solid-state CP-MAS 13C NMR, solid-state CP-MAS 29Si NMR, EDX, DTG, TGA, and acid–base volumetric studies. An environmentally benign catalytic protocol for the synthesis of biscoumarin scaffolds through a tandem reaction between 4-Hydroxycoumarin and structurally diverse aldehydes was developed in which the synthesized material SiO2-BHSB was observed to work as an efficient and reusable catalyst. The structures of the synthesized biscoumarin derivatives were established from their physical and spectrometric data. The synthesized catalytic material was observed to show sustained catalytic activity even after five cycles of its recovery and reuse. In comparison with the earlier reported methods, a tiny amount (2.5 mol%) of catalyst is sufficient to bring out the transformation smoothly in an aqueous-based solvent, ease of recovery, and reusability of the catalyst are additional salient features of the present protocol.

Evaluating the Presence and Contents of Phytochemicals in Honey Samples: Phenolic Compounds as Indicators to Identify Their Botanical Origin.

Honey is a natural product well known for its beneficial properties. It contains phytochemicals, a wide class of nutraceuticals found in plants, including compounds with highly demonstrated antimicrobial and antioxidant capacities as phenolic compounds and flavonoids. The main goal of this work is the development of a miniaturized and environmentally friendly methodology to obtain the phenolic profile of Galician honeys (Northwest Spain) from different varieties such as honeydew, chestnut, eucalyptus, heather, blackberry and multi-floral. The total phenolic content (TPC) and antioxidant activity (AA) were also evaluated. As regards sample preparation, miniaturized vortex (VE) and ultrasound assisted extraction (UAE) employing aqueous-based solvents were performed. Individual quantification of 41 target phenolic compounds was carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results revealed the presence of 25 phenolic compounds in the 91 analyzed samples, reaching concentrations up to 252 µg g−1. Statistical tools such as analysis of variance (ANOVA) and principal component analysis (PCA) were employed to obtain models that allowed classifying the different honeys according to their botanical origin. Obtained results, based on TPC, AA and ∑phenolic compounds showed that significant differences appeared depending on the honey variety, being several of the identified phenol compounds being responsible of the main differentiation.

Toward a facile fabrication route for all-cellulose composite laminates via partial dissolution in aqueous tetrabutylphosphonium hydroxide solution

The potential for a facile aqueous-based solvent processing route for the synthesis of all-cellulose composites (ACCs) is explored using aqueous solutions containing tertabutylphosphonium hydroxide (TBPH). Specifically, ACC laminates are prepared via the partial dissolution of a woven textile of cellulose II using aqueous TBPH solutions. The dissolved cellulose was then regenerated to reform a cellulose II matrix phase in situ that acts to bond the original undissolved fibres. The hygroscopic behaviour and dissolution analysis of the solvent system showed wide range in the choice of processing conditions suited to the production of ACC laminates via TBPH. The effect of solvent concentration on the microstructure, crystallinity and tensile properties of ACCs is reported. The use of TBPH enables reductions in the processing cycle time and improved control over the properties of ACCs, indicative of a promising solvent system for the upscaled production of ACCs and their laminates.

Biomimetic Production of Silk-Like Recombinant Squid Sucker Ring Teeth Proteins

The sucker ring teeth (SRT) of Humboldt squid exhibit mechanical properties that rival those of robust engineered synthetic polymers. Remarkably, these properties are achieved without a mineral phase or covalent cross-links. Instead, SRT are exclusively made of silk-like proteins called "suckerins", which assemble into nanoconfined β-sheet reinforced supramolecular networks. In this study, three streamlined strategies for full-length recombinant suckerin protein production and purification were developed. Recombinant suckerin exhibited high solubility and colloidal stability in aqueous-based solvents. In addition, the colloidal suspensions exhibited a concentration-dependent conformational switch, from random coil to β-sheet enriched structures. Our results demonstrate that recombinant suckerin can be produced in a facile manner in E. coli and processed from mild aqueous solutions into materials enriched in β-sheets. We suggest that recombinant suckerin-based materials offer potential for a range of biomedical and engineering applications.

Application of reversed phase chromatorotorTM for the isolation of natural products by spin chromatographic system

A new technology for the preparation of ChromatorotorTM (WO 2013/036803 A8) with a choice of chromatographic phases for Centrifugal Preparative Thin-layer Chromatography (CPTLC) or Rotational Planar Chromatography (RPC) opened a new window for fast, reliable, and economic separations of various classes of natural products. In order to prepare ChromatorotorsTM, together with the separation of compounds in the same instrument, an improved version of CPTLC, named Spin Cheromatography System (UM 8390), was developed. Polar and/or semi-polar compounds with close Rf values, as well as extracts and column fractions were separated and/or purified in a preparative and/or semi-preparative scale using the C18 silica gel rotors in RP mode, eluted with mixtures of aqueous-based solvents. Three model examples of this application, using RP ChromatorotorsTM, for the isolation of the diastereoisomeric alkaloids banistenosides I and II from Banisteriopsis caapi, saponins III and IV from Fagonia cretica, and the sesquiterpenes artemisinin (V) and artemisinic acid (VI) from Artemisia annua.

Preparation and Application of Reversed Phase ChromatorotorTM for the Isolation of Natural Products by Centrifugal Preparative Chromatography

A method of preparation of rotors with a reversed phase (RP) solid silica gel sorbent layer has been developed for centrifugal preparative chromatography (CPC), also known as rotational planar chromatography (RPC). The rotors consist of binder free RP solid SiO2 layers of different thicknesses packed between two supported circular glass discs and can be used in any appropriate device for centrifugal chromatography, like Chromatotron and CycloGraph. Polar and /or semi-polar compounds with close R(f) values, as well as extracts and column fractions were separated and/or purified in a preparative and/or semi-preparative scale using the RP rotors, eluted with mixtures of aqueous-based solvents. We herein report three examples of its application, using RP Chromatorotors, for the isolation of the diastereoisomeric alkaloids banistenosides I and II from Banisteriopsis caapi, saponins III and IV from Fagonia cretica, and the sesquiterpenes artemisinin (V) and artemisinic acid (VI) from Artemisia annua.

Effects of the molecular format of collagen on characteristics of electrospun fibres

Electrospinning is a process that is used to create nanofibres, which have the potential to be used in many medical and industrial applications. The molecular structure of the raw material is an important factor in determining the structure and quality of the electrospun fibres. In this study, we extracted collagen from a cold water fish species, hoki (Macruronus novaezelandiae), and prepared it in several different molecular formats (native triple helical collagen, denatured whole chains, denatured atelocollagen chains and gelatin) for electrospinning. Low molecular weight gelatin and atelocollagen did not form fibres. Treatment with 1,1,1,3,3,3 hexafluoro-2-propanol or 40% acetic acid denatured collagen molecules into intact α-chains prior to the electrospinning process. When using intact denatured collagen chains, 10% acetic acid was an effective aqueous-based solvent for producing uniform fibres. This information will be useful for the development of a non-toxic, aqueous solvent system suitable for industrial scale-up of the electrospinning process. Our results show that this low imino marine collagen is a suitable biopolymer for producing electrospun fibres.

Novel solvent systems for in situ extraterrestrial sample analysis

The life marker chip (LMC) is being designed to test for the chemical signature of life in the soil and rocks of Mars. It will use an antibody array as part of its detection and characterisation system and aims to detect both polar and non-polar molecules at the sub-ppm to tens of ppb level. It is necessary to use a solvent to transfer organic compounds from the Martian samples to the LMC itself, but organic solvents such as dichloromethane or hexane, commonly used to dissolve non-polar molecules, are incompatible with the LMC antibodies. Hence, an aqueous-based solvent capable of dissolving the biomarkers that might exist in the soil or rocks of Mars is required. Solvent extractions of a Martian soil analogue, JSC Mars-1, spiked with a range of standards show that a 20:80 (vol:vol) mixture of methanol and water is incapable of extracting compounds insoluble in water. However, addition of 1.5 mg ml −1 of the surfactant polysorbate 80 produces extraction efficiencies of the aliphatic standards, hexadecane and phytane, equal to 25–30% of those produced by the common organic solvent mixture 93:7 (vol:vol) dichloromethane:methanol. Extraction of squalene and stigmasterol using the polysorbate solution is less efficient but still successful, at 5–10% of the efficiency of 93:7 dichloromethane:methanol. Such aliphatic compounds with occasional functional groups represent the compound classes to which most fossil organic biomarkers belong. The polysorbate solution did not extract the aromatic compounds pyrene and anthracene with great efficiency. A solvent of 20:80 methanol:water with 1.5 mg ml −1 polysorbate 80 is therefore capable of selectively extracting aliphatic biomarkers from Martian samples and transferring them to the antibody sites on the life marker chip.

Avaliação das propriedades de intumescimento e permeabilidade de filmes isolados de polimetacrilato contendo polissacarídeo da raiz de Lótus (Nelumbo nucifera)

Polissacarídeo extraído da raiz de Lótus (Nelumbo nucifera) adicionado a polimetacrilato foi utilizado para a obtenção de filmes isolados, constituindo material candidato ao revestimento de formas farmacêuticas sólidas orais, sendo estas voltadas à liberação modificada de fármacos, potencialmente suscetíveis à degradação pela microflora presente exclusivamente na região distal do trato gastrintestinal. A adição do polissacarídeo ao polímero de base, dispersão aquosa Eudragit®RS 30D, ocorreu em diferentes proporções: 100:0, 90:10, 80:20, 70:30. Os filmes isolados foram caracterizados pela determinação do índice de intumescimento e pela transmissão de vapor de água. Os resultados registraram, para as diferentes associações testadas, características de transparência (opacidade) e de flexibilidade alteradas e dependentes do aumento da concentração do polissacarídeo: 100:0>90:10>80:20>7030, o mesmo ocorrendo no tocante à permeabilidade ao vapor d'água. Todavia estas diferenças não foram significativas entre si, demonstrando manutenção das propriedades físico-químicas do polímero sintético contendo polissacarídeo, o que permite sugerir o material obtido como candidato potencial ao desenvolvimento de sistema para liberação colônica.

Inertial Effects on Polymer Chain Scission in Planar Elongational Cross-Slot Flow

The molar mass and molar mass distribution of polymers subjected to chain scission in planar elongational flow are profoundly affected by the inertial character of the flow, as quantified by the Reynolds number. The degradation of dilute poly(ethylene oxide) (PEO) chains in aqueous-based solvents of varying viscosity was quantified in the planar elongational flow of a cross-slot flow device by gel permeation chromatography with multiangle laser light scattering detection. At low Reynolds number (Re ∼1000), the observed scaling was e ∝ Mw,f-1.04±0.07. Differences of this kind, first quantified by comparing results from stagnation point elongation flows and contraction flows, have previously been attributed to different molecular me...

Oligonucleotide Imprinting in Aqueous Environment

AbstractThe development of synthetic receptors that recognize nucleotide bases and their derivatives is an important area of research [1-3]. Applications are envisioned in separation science, biosensors, drug therapy and genetic engineering. Previously in this laboratory, we have developed a molecularly imprinted synthetic receptor for 9-ethyladenine (9-EA). The network polymer has an affinity for adenine and its derivatives with an average association constant (Ka) of 75,000 M–1 in CHCl3 [4]. When a 9-EA imprinted polymer was used as the chromatographic support, adenine eluted at 27 minutes using 92.5/5/0/2.5 CH3CN/H2O/CH3CO2H as the mobile phase, while cytosine, guanine and thymine derivatives all eluted close to the void volume (2.0 min). In addition, imprinted polymers have been made with complementary binding sites for cytosine and guanine [5], as well as other nucleotide base analogues [6].The extension of these results to construct robust receptors for oligonucleotides requires fundamental changes in imprinting strategies. Most importantly, since oligonucleotides are water soluble, strategies that employ EGDMA/MAA formulations in organic solvents will need to be replaced with those that do not compromise the interactions between template (the oligo) and functional monomer.Initially, the imprinting of a 2'-deoxyadenosine dimer (1) was attempted. Due to the hydrophilicity of a DNA oligomer, it was difficult to find a suitable organic solvent that would solubilize the oligomers without disrupting the template's interaction with the polymer matrix [7]. To combat the solubility problems and to insure the homogeniety of the polymerization solution, we examined various polymer formulations with organic and/or aqueous-based solvents that would dissolve the template without disrupting these key interactions.