AUCTORES
Review Article
*Corresponding Author: Krishna Shailaja, Department of pharmaceutics, RBVRR Women’s college of pharmacy, Affilated to Osmania University, Hyderabad India.
Citation: Krishna Shailaja, M. Usha, P. Sankeerthana, R. Jaya Sri, S. Niharika and S. Madhuri (2023), Review on Solubility Enhancement Techniques for Poorly Soluble Drugs, J. Pharmaceutics and Pharmacology Research, 6(3); DOI:10.31579/ 2693-7247/126
Copyright: © 2023, Krishna Shailaja. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 03 April 2023 | Accepted: 15 April 2023 | Published: 26 April 2023
Keywords: thymoquinone; vascular; health; vascular endothelial cells; cardiovascular diseases; vascular smooth muscle
Solubility of the drug is important factor that control the formulation of the drug as well as therapeutic efficacy of the drug. Many techniques are used for enhancing the poorly soluble drugs.So, by enhancing solubility we can improve dissolution rate and further oral bioavailability. In this article solubility enhancement techniques were discussed in detail.
An important physiochemical property of drug substance is solubility,especially aqueous system solubility. To achieve therapeutic efficacy a drug should have a property of aqueous solubility. For drug to enter systemic circulation and exert a therapeutic effect it must be in a solution.Therefore, solubility defined as ‘’concentration at which the solution phase is equilibrium with solute at a stated temperature and pressure’’. Solubility is the property of a solute (solid, liquid or gaseous) to dissolve in a solvent (solid, liquid or gaseous) to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the solvent used, temperature and pressure1,2.
If the solubility of drugs substance is less than desirable, consideration must be given to improve its solubility. The methods to accomplish this, depends on chemical nature of drug and type of drug product under consideration. Chemical modification of drug into salt or ester form is frequently used to increase solubility. A drugs solubility is usually determined by the equilibrium solubility method, by whichan excess of drug is placed in solvent and shaken at constant temperature over a long period until equilibrium is obtained. 3,4.
Knowledge of the solubility of a drug is also important during manufacturing of solid dosage forms such as orally administered drugs, liquid dosage forms such as injectables and other dosage forms. Solubility enhancement remains one of the primary areas of focus during the formulation development phase, there are several situations that may require solubilityreduction and enhancement. 5,6.
Solubility Criteria As Per The Usp
Descriptive term | Part of solvent required per part of solvent |
Very soluble Freely soluble Soluble Sparingly soluble Slightly soluble Very slightly soluble Practically insoluble
| <1> 1-10 10-30 30-100 100-1000 1000-10,000 10,000 and over |
Importance of Solubility
With the cryo-spraying technology it was possible to formulate the drug as solid dispersion into amphiphilic lipid based micro spheres to improve dissolution profile.
Factors Affecting Solubility Enhancement of Drugs
1.Temperature
2. Polarity of drug and solvent
3. PH
4.Drug particle size
5.Effect of pressure
6.Crystal structure
7.Nature of solvent
8.Molecular structure
9.Co-solvency
10.Molecular size
11.Common ion effect
1.Temperature:Most substances are endothermic, or absorb heat in the process of dissolution, meaning an increase in temperature from room temperature storage to oral consumption and moving into body heat results in an increase in solubility.
2.Polarity of Drug And Solvent: In addition, ion trapping is important for the drug to show its effect properly. In the stomach or intestines, the drug is non-ionized again to prevent it from going back to the GIT and to ensure it is absorbed by body. Lipid soluble substances contain non-ionized molecule(NaCl), and hydrophilic substances contact ionized molecules (Na+, CL-), meaning the more lipid soluble a drug is, the more absorption there will be. The more water soluble(hydrophilic) a drug is, the less absorption there is
3.Ph Levels: PH measures the amount of hydrogen content in a solution. The less Hydrogen ions the greater will be the Ph. Solutions with strong pH levels fully dissociate and those with weak pH levels only partially dissociates. The pKa value is used to determine the strength of an acid. A lower pKa value means the drug substance is a stronger acid, which more fully dissociatesin water.
4.Drug Particle Size: The solubility of the drug is directly tied to the particle size. Larger particles are less solubilized, especially if the temperature, pressure and polarity for the solutes is the same. The ability for a drug to be soluble allows for simple diffusion of the drug with no energy or carrier protein neededto enter and be absorbed by blood stream.
5.Effect of Pressure:In case of solids and liquids solutes there is no effect of pressure on the solubility but in case of gaseous solutes. When the pressure increases there is increase in the solubility and with decrease in pressure there is a decrease in solubility.
6.Crystal Structure: Amorphous form of drugs is more soluble than crystalline form.
Solubility: Solvates > Anhydrous > hydrates
Crystalline structure is the best mechanism to improve the solubility.
7.Nature of Solvent:The solubility of a solute in a solvent depends on the nature of solute and the solvent. The polarity of the solute and polarity of solvent effect the solubility. Examples:Polar solvents dissolve polar solutes whereas non polar solvents does the same.
8.Molecular Structure: Slight modification in the molecular structure of solids lead to marked changes in the solubility of a given solvent.
Introduction of hydroxy group increases water solubility.
Ex: Phenol and Benzene
9.Co-solvency:It is a systemin which water miscible or partially miscible organic solvent is mixed with water to form a modified aqueous solution known as co-solvency. Cosolvents have some degree of hydrogen bonding which accepts some hydrocarbon regions. This result in some of physical properties those are intermediate to pure organic solvent and water. It can be reduced by water-water interaction.
Ex: Cosolvents are Ethanol, Sorbitol, Glycerine.
10.Molecular Size: Solubility decreases as the molecular size increases. On the other side solvent molecules wrap around molecules of smaller size more easily increasing solubility of the substance.
11.Common Ion Effect: added to another ionic compound with a common ion, the solubility of substance decreases significantly. The common ion effect can be explained by LeChatelier’s principle of chemical equilibrium. As the reaction of a drug shifts to left side.
Bcs -Biopharmaceutical Classification System
The bioavailability of an orally administered drug depends primarily on its solubility in the gastrointestinal track and its permeability across cell membrane this forms basic for biopharmaceutical classification system9,10. Based on intestinal permeability and solubility of drugs, developed biopharmaceutics classification system. The table shows approach employed to overcome formulation challenges in each class drug.
Class | Solubility | Permeability | Absorptionpattern | Examples |
I | High | High | Well absorbed | Diltiazem, Propranolol, Metoprolol |
II | Low | High | Variable
| Nifedipine, Naproxen, Carbamazepine |
III | High | Low | Variable | Insulin, Metformin, Cimetidine |
IV | Low | low | Poorly absorbed | Taxol, Chlorothiazide, Furosemide |
Table 1: BCS Classification of drugs
Ex:Diltiazem, propranolol, metoprolol.
Ex:Nifedipine, naproxen, carbamazepine.
Ex: insulin, Metformin,cimetidine.
Ex: Taxol, chlorothiazide, furosemide.
The BCS classification depends mainly on solubility permeability, dissolution rate this corelate to respective dimensions such as dose number absorption number, dissolution number.
Determination of Solubility
For a pharmacist and pharmaceuticalpersonthe question of solubility is paramount importance. Solubility is not only necessary for dispensing and preparing of medicines but also the effect in separation of substance in qualitative and quantitative analysis. It is one of the best techniques for determining the purity.
Techniques of Solubility Enhancement
1)Physical methods
a)Particle size reduction
2)chemical methods
3)Other methods
Size reduction
Micronisation: Micronization is a process of reducing the size ofparticles from larger substance to 50 microns in diameter. Micronization increases the solubility by decreasing the surface area. Lower the particle size faster the solubility. Micronizationtechnology includes wide range of equipment and process to account for the range of material properties, size and shape requirements and other specifications needed for pharma products.
Micronization increases the rate of dissolution of drugs by decreasing drug particle size.
Micronization techniques:
1.Ball mill
2.Rotary cutter mill
3.Hammer mill
4.Fluidized bed jet mill
5.Super critical fluid
Ball mill:
Construction: Ball mill consists of a hallowcylinder, which is mounted on a metallic frame in such a way it rotates on its own axis. The cylinder is made of a metal and is usually lined with stainless steel or sometimes the cylinder is lined with rubber or porcelain. Balls occupy about 30-50% of volume and diameter of the ball in 12-125nm. Shell is rotated at a speed of 60-100rpm.The weight of the balls is kept constant.
Ball Mill
Advantages:
Disadvantages:
Variants: Harding mill, continuous ball mills, vibrating ball mills.
Hammer mill:
Construction:. The rotor is rotated at a speed of 8000-15000rpm inside the drum while material is fed through feed chopper. In pharmaceutical industry different shapes are used for grinding dry materials, wet filter cakes, etc.
Two basic shapes are
1.STIRR UP.
2.BAR.
For tablet granulation bar shaped hammers are used widely. The hammer blades can be with flat edge or sharp edge or both on each side. Hammers may be rigid or swing type.
The unit enclosed in chamber containing a grid or removable screen through which the material must pass. These screens are not oven type. The fitness of the product can be regulated by altering:
Uses: Fineto moderate grinding of may be obtained, depending on the speed of the hammer. The particle size may vary from 10 to 400 mm.
Advantages:
Disadvantages:
Jet Mill:It is also known as fluid energy mill.
Principle: The principle involved in fluid energy mill is impact and attrition. In this fluid energy millwith high velocity the feed stock is suspended in air stream. Milling takes place between suspended particles with high velocity collisions.
Construction: The surface of mill is made up of soft stainless steel or tough ceramics. Mills are contructed with these materials so that they can easily removed when they are eroded and the contact surface area is more.
Grinding nozzles (usually two to six) may be placed tangentially and /or opposed to the initial flow path of a powder.. Inert gases are used to control or eliminate the oxidation of compounds.
Jet Mill
Advantages:
Disadvantages:
Super Critical Fluid Extraction
Principle: Super critical fluid extraction is the process of separating one component from another (the matrix) using super critical fluids as the extracting solvent.
EXAMPLE:co2 It is widely used because it is low cost, nontoxic and low critical parameters.
Parts of sff:
EXAMPLE: methanol in concentration 1-10%
Super Critical Fluid Process
Advantages:
Limitations:
Applications:
Flavaniod Extraction: Quercetin from onion skin
. Recycling of Sff Can Be Done By
Heat exchange are used to maintain temperature and prevent excessive cooling at throttling value called as Joule-Kelvin effect.
Sonocrystalization In Solubility Enhancement:
The novel approach for particle size reduction on the basis of crystallization by using ultrasound is Sono-crystallization.
Sonocrystalization In The Nucleation Phase: In nucleation, molecules gather together in cluster in a defined manner these clusters need to be stable under current experimental conditions to reach the critical cluster size or they will redissolve and it is the point in the crystallization process that defines the crystal structure.
Applications:
Nano Suspension
This method is mainly categorised into
Top-down process
Bottom-up process
High Pressure Homogenization
Homogenization is the process of emulsifying two immiscible liquids(i.e., liquid that are not soluble in one another) are uniformly dispersing solid particles throughout a liquid. The process of homogenization was invented and patented by Auguste Gaudin in 1899 when he described process for homogenising milk. Gaudin’s machine a three-piston thruster outfitted with tiny filtration tubes, was shown at the world fair in Paris in 1900.
THEORIES
1.Cultivation theory
2.Globule disruption by turbulent eddies
1.cultivation theory:The liquid encounters intense cultivation because of large pressure drops through the valve when the pressure drop is large enough, the vapour pressure of liquid exceeds the ambient pressure causing formation of vapour bubble (cavities in the liquid). When the cultivation bubbles implode (collapse of the cavities), shock waves are generated in the liquid. The shock waves break apart the dispersed droplets.
2.Globule disruption by turbulent eddies:.This theory predicts how the homogenising effect varies with the homogenising pressure.
High Pressure Homogenizer
Working: the nano homogenized product enters the valve seat at high pressure and low velocity. The intense release cause turbulence and localized pressure which tear apart the particles. The homogenized product impinges onthe impact ring and exit at a pressure sufficient for movement to the nextstep.
Advantages:
Disadvantages:
Microfludization
Microfluidization is a method used for production of micro and nano scale materials. It is commonly used in pharmaceutical industry to make liposomal products emulsions, and in food industry to produce dairy products. A microfluidizer is used to create highpressure to disintegrate fibers, using shear forces. It is patent in mixing technology which uses the microfluidiser.
Microfluidisation
APPLICATIONS
Solvent and Anti Solvent
It is used for preparation of nano particles of drug which have low aqueous solubility those are drugs which belongs to BCS class II and class IV. In this method we take a solvent in which drug is completely soluble. This solvent can be any organic solvent like acetone, ethanol, dichloromethane, as this name suggest we take an antisolvent which is usually aqueous medium such as water in which the drug is insoluble. Here the drug is having solubility in solvent and solvent is having more solubility in water
Procedure:
EXAMPLE: acetonitrile, ethanol, ethyl acetate, water.
Polymorphs
Among the various techniques used to enhance solubility of poorly soluble drugs are physical and chemical modification of drugs, and method such as particle size reduction, salt formation, solid dispersion, use of surfactants and complexation. Crystalline polymorphs have the same chemical composition, but different internal structure and therefore possess different physicochemical property because of the different lattice structure, different molecular conformations. Polymorphic forms of drugs can crew interesting for drug developers because their thermodynamic and physicochemical properties.
Polymorph screening
The process seeks to determine whether a given compound exist in polymorphic form. The concept of polymorphic screening was introduced by Pepinsky in 1955 and first applied by Schmidt in the context of covalent bond formation in solid state. Combinatorial chemistry and high through put screening used in drug discovery have resulted in an increase of poorly water-soluble drugs. .
Pseudopolymorphs
Pseudo polymorphs is the phenomenon where in aa compound is obtained in crystalline forms that differ in the nature or stoichiometry of included solvent molecules. The solvent can exist in different crystalline form called as pseudo polymorphs.
Complexing Agents
Complexation relies on relatively week forces such as van der wall forces, hydrogen bonding and hydrophobic interactions. It is of two types
1.Inclusion complexation 2. Staching complexation
Inclusion Complexation
This are formed by the insertion of the non-polar molecule or the non-polar region of one molecule into the cavity of another molecule or group of molecules. Cyclodextrins are most commonly used host molecules. Based on the structure and properties of drug molecule it can form 1:1 or 1:2 drug cyclodextrin complex.
Staching Complexation
Complexation formed by dissolving organic drug with water. it is squeezed out by strong water-water interaction force. It forms aggregates and reduce contact between non-polar hydrocarbon moieties and polar water moieties the larger non polar regions opposed by entropy and random arrangement was formed. The formed complexes stached can be homogenous or mixed. It is a self-association complexation. Ex: nicotinamide, Anthracene, Caffeine, theobromine10.
Microemulsion
Microemulsion is defined as isotropic mixture of natural or synthetic oils, surfactant and co-surfactant. Microemulsions are liquid droplets in a diameter of 10-100nm. They are transparent translucent as the droplet diameter are less than one-fourth of the wavelength of light, they scatter little light.
Advantages:
Disadvantages:
Eutectic mixtures
A eutectic or eutectic mixture is a mixture of twoor more phases at a composition that has lowest melting point .it is a where the phases simultaneously crystalize from molten solution. Their formation occurs via non covalent forces mainly hydrogen bonding, ionic and Vander Waalsforces and aromatic interaction.This,systems can be considered as of physically blended with high thermodynamic functions. eutectic mixtures have been known for long time in pharmaceutical field. However, its potential as a system to improve the solubility and dissolution of poorly water-soluble drugs remains little explored. Recently the number of studies involved in the preparation of eutectic mixtures to improve solubility and oral bioavailability of poorly soluble drugs has increased considerably including drug carrier and drug-drug mixtures.in this review is discussed the potential of eutectic mixtures as an alternative pharmaceutical solid system to enhance drug solubility, dissolution rate or oral bioavailability11.
Lovastatin is widely used to control hypercholesterolemia and is first line treatment of coronary artery disease and atherosclerosis which acts by inhibiting hydroxy glutaryl coenzyme A reductase.
Differential scanning calorimetry analysis
Differential scanning calorimetry curves of the obtained solid wereacquired using DSCQ 200 equipped with a TA refrigerator cooling system 90,using aluminium crucibles with 2mg of sample under dynamic nitrogen atmosphere and heating rate of 10 degrees per minute in the temperature from 40 to 200 degree Celsius
DSC is the primary technique used to identify eutectic formation hence it is applied to screen LOV and co -formers or excipients in binary mixture composition (1:1).
Solid Dispersion
In solid dispersion technique poorly-soluble drugs is dispersed in highly solid hydrophilic matrix which enhanced the dissolution of the drug and can yield molecular and non-molecular level mixing. Ex: PEG 4000 increases the rate of dissolution. Solubility of Griseofulvin, ketoprofen, Aceclofenac, Oxcarbazepine, Albendazole, bifonazole induced by solid dispersion technique.
It was prepared by
1.Hot melt method
2.Solvent evaporation
3.Hot melt extrusion
Hot Melt Method:
The excipients are heated to a temperature above its melting point and the drug is incorporated. A molecular dispersion can be achieved or not depends on the degree of saturation and rate of cooling used in the process. When drug and vehicle which is meant for melting it should contain low melting point and insoluble in organic solvents. It was cooled quickly and prepared for suitable dosage form
Hot Melt Extrusion
Hot melt extrusion of miscible components results in amorphous solid solution formation, whereas extrusion of immiscible components leads to amorphous drug dispersed in crystalline excipient. The process has been useful in preparation of solid dispersion in single step. This method of choice in the polymer industry, but Speiser and Huttenrach were the 1st person to use this technology for pharmaceutical purpose. A melt extrusion consists of following section: an opening to feed raw materials, a heated barrel that consist of extruder screws to convey and mix the feed materials and an exit port, which consist of optimal die to shape the extruding mass. the active ingredient and the carrier are feeding to the extruder at aconstant rate. When a mixture of active ingredient and carrier is conveyed through heated screws, it is transformed into its fluid like state. This state allows intimate homogenous mixing by the high shear of extruder screws. An exit port which consists of optional die, shapes the melt in required form such as granules, pellets, films or powder. 12.
Hot Melt Extrusion
Advantages of solid dispersion:
Disadvantages:
By Change Of Ph
Poorly water-soluble drug may potentially dissolve in water by implementing a Ph change. To access the solubility the buffer capacity and tolerable Ph are important to be considered. Solubilized excipients that increase environmental pH with in the dosage form to a range higher than pKa of weakly acidic drugs increase the solubility of that drug,.
Advantage:
Disadvantage:
For weekly acidic drugs
For weakly basic drugs:
Use of buffer
They maintain the Ph of the solution overtime and it reduces or eliminate the potential for precipitation upon dilution.. Change of pH by onefold increase solubility by 10fold if it changes by one pH unit, that decrease ionization of the drug and solubility decreases by 10-fold.
Derivatization
It is a technique used in chemistry which transforms a chemical compound in to a product of similar chemical structure, called derivative. Derivatives have different solubility has that of adduct.
Co-Crystalization: Co-crystallization alters the molecular interactions and is considered to optimize drug properties as an alternative metho
Co-crystallization overcomes various physical, chemical, or physiological drawbacks of an API. Mechanism of co solvency favours the dissolution of a non-polar solute by lowering the interfacial tension. If one of the components is liquid and the other is solid then it is termed as cocrystals.Pharmaceutical co-crystals basically consist of two components that are the API and the co crystal formers12.
Different techniques for co-crystallization:
Co-crystals characterization parameters:
Co-Solvency: It has found its main use in parenteral dosage forms because of low toxicity of many cosolvent and relatively greater ability of co-solvents to solubilise nonpolar drugs. Commonly used cosolvents glycerol, propylene glycol, PEG 400, dimethyl sulfoxide, dimethyl acetamide, ethanol, n-octanol are the commonly used cosolvents
Advantages:
Disadvantages:
Hydrotrophy:
It is a solubilization phenomenon where addition of a large amount of second solute results in an increase in the aqueous solubility of existing solute. Hydrotropic agents are ionic organic salts.
Aromatic anionics: sodium benzoate, sodium salicylate, sodium benzene-sulphonate, sodium benzene di-sulphonate, sodium cinnamate
Advantages:
Mixed hydrotrophy: It is new, simple, cost effective, safe, accurate, precise method which involves the blends of hydrotropes which gives synergistic effect on solubility of poorly water-soluble drugs.
Nanotechnology:
It refers widely to study and use of materials and structures at the nano scale level of approximately 100 nm or less. Forvery low solubility, oral bioavailability many techniques are used such as enhancement by micronization which is not sufficient because micronized product has very low effective surface area for dissolution and further step taken was nanonisation which reduce the particle size from micro to nano. The methods of preparation like milling, high pressure homogenisation, vacuum deposition, high temperature evaporation may be used.
Advantages:
It results in production of the nano or micro sized spherical particles with smooth surfaces and narrow particle size distribution and high specific surface areas, consequently increasing the dissolution rate and solubility.
Disadvantages:
The agglomeration problem is inherent and difficult to overcome.
Solubulizing agents:
We use different types of solubilizing agents such as surfactants, Crospovidone, croscarmellose sodium and sodium starch glycolate etc. The aqueous solubility of the antimalarial agent halofantrine was increased by the addition of caffeine and nicotinamide14.
Solubilization by surfactants: Most surfactants consist of hydrocarbon segment connected to polar group.
Microemulsion: The addition of surfactant, which predominately soluble in the internal phase when compared with co surfactant. It results in the formation of an optically clear, isotropic, thermodynamically stable emulsion. It is termed as microemulsion because of the internal phase is less than 0.1micron droplet diameter. The surfactant and the co surfactant alternate each other and form a mixed film at the interface, which contributes to the stability of microemulsion.
Non-ionic surfactants, such as tweens (polysorbates) and labrafil(polyoxyethylated oleic glycerides), with high hydrophile-lipophile balances are often used to ensure immediate formation of oil-in-water droplets during production.
Advantages:
Solvent Deposition
Reduction of particle size remains the accepted method for increasing dissolution rates. However, upon micronization hydrophobic drugs have a tendency to form clump when exposed to the dissolution medium. Sekiguchi and Obi proposed that the incorporation of a microcrystalline or molecular dispersion of a poorly soluble drugs in solid matrix of water-soluble carrier would increase the dissolution rate and absorption of the drug. Since then, modifications of the technique have been suggested under a variety of names, including solid solutions, eutectics, co-precipitates, and fast release solid dispersions.
Advantages:
preparation: Fine powders of the drug and different water-soluble adsorbents or carriers are accurately weighed in certain ratios. Drug is added to organic solvent in a beaker sufficient enough to dissolve the drug. Then required quantity of adsorbent is added to above drug solution. This slurry or gel are stirred by a magnetic stirrer and evaporated by a stream of filtered air or water bath. Temperature maintained for evaporation is generally a little higher than the boiling point of solvent to allow organic solvent to evaporate. The samples are then placed in a heated vacuum desiccator or vacuum oven to facilitate the drying process. The solid masses are then remixed by tumbling end over end for few minutes. Then solvent deposited systems is stored in desiccators for future use15.
Investigators | Water insoluble drugs | Solvents used | Carrier used |
Monkhouse | Indomethacin, griseofulvin, chloramphenicol, hydrochlorothiazide, aspirin, reserpine | Acetone, chloroform, dichloromethane | Fumed silicon dioxide, silicic acid |
Johansen | Phenylbutazone, norethindrone, digoxin | Acetone, chloroform, | Lactose, starch, silicon dioxide |
Lia | Corticoids (prednisolone, prednisone, hydrocortisone) | N,N-dimethylacetamide polyethylene glycol 400 | Non porous and porous amorphous silicas |
Alsaidan | indomethacin | Alcohol solution | Kaolin and microcrystalline cellulose |
Dastmalchi | glibenclamide | chloroform | Microcrystalline cellulose |
Cui | Nitrendipine | Ethanol and dichloromethane | Microcrystalline cellulose, light anhydrous silicic acid, lactose and low substituted hydroxypropyl cellulose |
Kakkar | chlordiazepoxide | dichloromethane | Starch-lactose granules |
Table 2: Literature on Solubility enhancement techniques
Characterization of solvent deposition system:
Applications:
Applications
Pharmaceutical nanotechnology provides opportunities to improve materials and technology where existing technologies reaching their limits. It raises new hope to pharmaceutical industries by providing new patentable technologies in view of revenue loss caused due to off patent drugs. This provides profound tools for understanding the cells between normal and abnormal or any insights of molecular basis.
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"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.