Use Of Cyclodextrins Research Articles

Clinical Effectiveness, Safety, and Compliance of Two Compounded Formulations of Tacrolimus Eye Drops: An Open-Label, Sequential Prospective Study.

Ophthalmic tacrolimus compounded formulations are usually made from the commercial intravenous presentation, which contains ethanol as a solubilizer due to the low solubility of tacrolimus. The use of cyclodextrins is presented as an alternative to ethanol, an ocular irritant excipient, to avoid its long-term irritant effects. Open-label, sequential, prospective study to compare effectiveness, safety, and adherence of a new formulation of 0.015% tacrolimus with cyclodextrins (TCD) versus 0.03% tacrolimus with ethanol (TE). The ocular evaluation was assessed by ocular signs, corneal staining, subjective questionnaires as Visual Function Questionnaire (VFQ-25) and Visual Analogue Scale (VAS) of symptoms, lacrimal stability, ocular redness, and intraocular pressure. Compliance was assessed by VAS of adherence and empirically (difference between theoretical and actual consumption). Clinical ocular signs and corneal staining score remained stable for most patients 3 months after switching formulations. The TCD formulation did not modify the tear stability and intraocular pressure of the treated patients compared to the TE formulation. TCD eye drops significantly decreased the subjective pain values on VFQ-25 scale and burning sensation on the VAS symptom scale in comparison to TE formulation after 3 months after the change to TCD formulation. The novel tacrolimus in cyclodextrins formulation is a promising alternative for treating inflammatory ocular pathologies refractory to first-line treatments.

β-Cyclodextrin-Modified Cotton Fabric for Medical and Hospital Applications with Photodynamic Antibacterial Activity Using Methylene Blue

The use of cyclodextrins in textiles for the development of biofunctional fabrics represents an interesting alternative for the advancement of dental, medical, and hospital materials. Cyclodextrins can interact with the chemical groups present in cotton fibers, leading to the formation of a nanostructured surface with specific functional properties, including antibacterial activity. Although there are numerous antibacterial textile finishes, the use of methylene blue as a cyclodextrin host molecule for photodynamic applications in textile materials remains to be investigated. This is because methylene blue is a photosensitive dye capable of generating singlet oxygen (1O2) when illuminated, which inactivates the pathogenic microorganisms that may be present in wounds. The objective of this study was to develop a biofunctionalized and photoactivatable cotton fabric with antimicrobial properties for use in the cosmetic or medical industries. The materials obtained were characterized via scanning electron microscopy (SEM), Fourier transform infrared spectroscopy with attenuated total reflection (FTIR-ATR), the determination of cotton fabric functionalization dyeing variables, colorimetry, UV-VIS spectrophotometry, degradation of 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA), photodegradation tests, and microbiological analysis. The results showed that the textile was functionalized with β-cyclodextrin, mainly evidenced by the appearance of the band at 1730 cm−1, indicating the formation of the ester group. Thus, when exposed to light, the non-functionalized material showed greater photobleaching, about 60%, compared to the material treated with cyclodextrin. This result was also reflected in the ABDA degradation kinetics, with the treated material showing 592.00% (first phase) and 966.20% (second phase) higher degradation than the untreated sample. Finally, the photodynamic activity was determined based on the antimicrobial properties of the textile, showing a reduction of more than 99% without exposure to light and 100% when exposed to light. It is believed that this study could open avenues for future research and the development of antimicrobial fabrics, as well as demonstrate the efficiency of the treatment with cyclodextrin in relation to photobleaching.

γCyclodextrin-assisted Aqueous Extract of Cinnamon for Cancer and Stress Management.

Our goal was to investigate the use of Cyclodextrin in creating an aqueous extract of Cinnamon with a high content of its bioactive ingredients, validated by cell-based assays. Due to their safety and cost-effectiveness, natural compounds have garnered attention for cancer therapy, which often faces challenges related to drug toxicity and resistance. Cinnamon (Cinnamomum verum; also known as Ceylon Cinnamon) is a commonly used spice with a history in folk medicine for treating various ailments. However, its active ingredients suffer from poor solubility, stability, and bioavailability, which limits its use and benefits. We prepared γCyclodextrin (γCD)-assisted aqueous extract of Cinnamon (CD-CIN) and compared its activity with the DMSO extract (DM-CIN). The cells were exposed to CD-CIN and DM-CIN extracts under normal and stressed (oxidative, metal, and hypoxic) conditions and then analyzed for stress and cancerous phenotypes using various molecular assays. We found that CD-CIN possesses considerable anticancer activity that involves the activation of tumor suppressor proteins and DNA damage response. Low, non-toxic concentrations of DM-CIN and CD-CIN caused comparable inhibition of migration and invasion capability of cells, supported by molecular marker analyses. Furthermore, protection against oxidative, metal, and hypoxia stress, as well as induction of differentiation, was recorded in both DM-CIN and CD-CIN treated cells, as compared to the control. We report CD-CIN as a new economic and easy Cinnamon-derived resource that possesses considerable anticancer and antistress activities and hence warrants further chemical, in vitro, and in vivo studies.

Development of cyclodextrin-electrokinetic chromatography-based strategies for the separation of ketorolac enantiomers

The development of analytical strategies enabling the chiral separation of ketorolac by electrokinetic chromatography is presented in this work. This anti-inflammatory drug is commercialised as racemic mixture but its physiological activity resides in the S-enantiomer. Different experimental conditions were investigated at acidic and neutral pH, including the use of cyclodextrins (CD) or amino acid-based ionic liquids (AAILs) ([TMA][L-Cit], [TMA][L-Arg], [TMA][L-Harg], [TBA][L-Cit], [TBA][L-Arg], and [TBA][L-Harg]) as the sole chiral selectors or the combination of a CD with AAILs or their cationic components (tetramethylammonium (TMA-OH) or tetrabutylammonium (TBA-OH)). The best conditions in terms of migration times and enantiomeric resolutions were obtained using 2 mM heptakis(2,3,6-tri-O-methyl)-β-CD (TM-β-CD) in 50 mM phosphate buffer at pH 7.0 or 2 mM TM-β-CD with 60 mM TMA-OH in 50 mM formate buffer at pH 3.0. The presence of TMA-OH in the separation medium affected considerably the electroosmotic flow (EOF) mobility which, in turn, significantly shortened the migration times for ketorolac enantiomers at pH 3.0 due to an inversion in the EOF. The multivariate optimization of the experimental conditions for the single system and for the combined system with TMA-OH enabled to obtain the separation of ketorolac enantiomers in less than 11 min with enantiomeric resolutions of 2.5 and 1.9, respectively. The single system was selected to evaluate its analytical characteristics in terms of limits of detection/quantification, accuracy, and precision, according to the International Council for Harmonization (ICH) guidelines, which resulted adequate to be applied to the analysis of pharmaceutical formulations.

In vitro and in silico studies of the inclusion complexation of 8-bromobaicalein with β-cyclodextrins

Baicalein, a flavone derived from Scutellaria baicalensis Georgi, exhibits potent anti-inflammatory, antiviral, and anticancer properties. Its derivative, known as 8-bromobaicalein (BB), has been found to have strong cytotoxic effect on MCF-7 human breast cancer cells. However, its limited solubility in water has hindered its potential for wider applications. To address this issue, we investigated the use of cyclodextrins specifically βCD, 2,6-di-O-methyl-β-cyclodextrin (DMβCD), and hydroxypropyl-β-cyclodextrin (HPβCD) to improve the solubility of BB through inclusion complexation. During 250 ns molecular dynamics simulations, it was found that BB can form inclusion complexes with all βCDs. These complexes exhibit two distinct orientations: chromone group insertion (C-form) and phenyl group insertion (P-form). The formation of these complexes is primarily driven by van der Waals interactions. DMβCD has the highest number of atom contacts with BB and the lowest solvent accessibility in the hydrophobic cavity. These results coincide with the highest binding affinity from the MM/GBSA-based free energy calculation method. Experimental phase solubility diagrams revealed a 1:1 stoichiometric ratio (AL type) between BB and βCDs, in which BB/DMβCD showed the highest stability. The formation of inclusion complexes was confirmed by differential scanning calorimetry and scanning electron microscope methods. Additionally, the BB/DMβCD inclusion complex demonstrated significantly higher anticancer activity against MCF-7 human breast cancer cells compared to BB alone. These findings underscore the potential of DMβCD for formulating BB in pharmaceutical and medical applications.

Carrier Systems for Advanced Drug Delivery: Improving Drug Solubility/Bioavailability and Administration Routes.

The disadvantages of some conventional drugs, including their low bioavailability, poor targeting efficiency, and important side effects, have led to the rational design of drug delivery systems. In particular, the introduction of drug delivery systems is a potential approach to enhance the uptake of therapeutic agents and deliver them at the right time and in the right amount of concentration at the required site, as well as open new strategies for effective illness treatment. In this review, we provide a basic understanding of drug delivery systems with an emphasis on the use of cyclodextrin-, polymer- and surfactant-based delivery systems. These systems are very attractive because they are biocompatible and biodegradable nanomaterials with multifunctional components. We also provide some details on their design considerations and their use in a variety of medical applications by employing several routes of administration.

Cyclodextrin-Induced Suppression of the Crystallization of Low-Molar-Mass Poly(ethylene glycol).

We examine the effect of alpha-cyclodextrin (αCD) on the crystallization of poly(ethylene glycol) (PEG) [poly(ethylene oxide), PEO] in low-molar-mass polymers, with M w = 1000, 3000, or 6000 g mol-1. Differential scanning calorimetry (DSC) and simultaneous synchrotron small-/wide-angle X-ray scattering (SAXS/WAXS) show that crystallization of PEG is suppressed by αCD, provided that the cyclodextrin content is sufficient. The PEG crystal structure is replaced by a hexagonal mesophase of αCD-threaded polymer chains. The αCD threading reduces the conformational flexibility of PEG and, hence, suppresses crystallization. These findings point to the use of cyclodextrin additives as a powerful means to tune the crystallization of PEG (PEO), which, in turn, will impact bulk properties including biodegradability.

Phthalates Adsorption on Nanostructures for Environmental Remediation: an ab initio Study

Phthalates are organic molecules found in various everyday materials, such as plastics, but they do not bond chemically to the product. Consequently, they are released and contaminate the environment. In humans, ingesting phthalates can stimulate a functionality similar to estrogen hormones, acting as endocrine disruptors, thus requiring selective adsorption. This paper demonstrates the use of cyclodextrins (CDs), which are useful due to their capacity for selective adsorption by the inclusion of organic molecules in their internal cavities to remove pollutants from water. Graphene (Gr) is also evaluated due to its interesting electronic properties and a large surface, making this nanomaterial ideal for molecule adsorption. Through ab initio simulations, three phthalate molecules, benzyl butyl phthalate (BBP), dicyclohexyl-phthalate (DCHP), and dipropyl phthalate (DPP) interacting with β-CD and Gr, were evaluated. The results indicate that a weak interaction occurs, through physical adsorption. β-CD interacting with phthalates tends to form a host-guest complex. In the case of Gr, weak adsorption is favored by π-π interactions and H-bonds. Therefore, this study shows that these nanosystems are promising for removing phthalate molecules from wastewater.

A DFT-Based Mechanism Analysis of the Cyclodextrin Inclusion on the Radical Scavenging Activity of Apigenin.

Natural flavonoids are renowned for their exceptional antioxidant properties, but their limited water solubility hampers their bioavailability. One approach to enhancing their water solubility and antioxidant activity involves the use of cyclodextrin (CD) inclusion. This study investigated the impact of CD inclusion on the three primary radical scavenging mechanisms associated with flavonoid antioxidant activity, utilizing apigenin as a representative flavonoid and employing density functional theory (DFT) calculations. Initially, the optimized geometries of CD-apigenin inclusion complexes were analyzed, revealing the formation of hydrogen bonds between CD and apigenin. In less polar environments, the inclusion complex strengthened the bond dissociation enthalpies of hydroxyl groups, thereby reducing antioxidant activity. Conversely, in polar environments, the inclusion complex had the opposite effect by lowering proton affinity. These findings align with experimental results demonstrating that CD inclusion complexation enhances flavonoid antioxidant activity in aqueous ethanol solutions.

DRUG-CYCLODEXTRIN COMPLEXES: CURRENT STATUS AND RECENT ADVANCEMENTS

Cyclodextrins are water-soluble oligosaccharides formed by the action of cyclodextrin glucosyl transferase enzyme (CGTase) on the medium containing starch. Cyclodextrins are proven to be a cost-effective breakthrough in the pharmaceutical industry by formulating them with polymers and drugs to improve the safety, bioavailability, and solubility of APIs. This review describes the current status and advancement of cyclodextrin research in drug delivery. The use of cyclodextrins to improve the solubility and dissolution properties of poor water-soluble products has been reviewed exhaustively with a specific focus on their physicochemical property, practical methods, toxicity, the drug-cyclodextrin compatibility and its applications.

Lipids in the reproduction of sires.

The main class of nutritional interest for lipids are fatty acids (FA), which correspond to 90% of triglycerides, the main form of lipid storage in both plants and animals. FAs serve as a source of energy in the diet of cattle; however, they also have an important non-caloric effect on animal organisms as they are important components of the physical and functional structures of cells and participate in the composition of steroid hormones. As such, research has studied the improvement of semen quality through the provision of polyunsaturated FAs in bull diets, as well as the use of FAs in semen extenders in order to reduce damage to sperm cells, which can alter lipid composition and the quality of frozen sperm. Therefore, the objective of this work was to review the effectiveness of lipids on reproductive efficiency, based on their effects on semen quality and hormonal production. Supplementation with polyunsaturated FAs positively alters semen composition and in vitro fertility; however, results vary according to the type of FA used, the method of administration, and its quality. Fish oil and linseed oil showed better results in qualitative parameters in fresh and thawed semen. The use of cyclodextrins to incorporate or extract cholesterol from plasma membranes can also improve the viability of cryopreserved semen.

Effect of Cyclodextrin Complex Formation on Solubility Changes of Each Drug Due to Intermolecular Interactions between Acidic NSAIDs and Basic H2 Blockers.

One of the solubilization of poorly water-soluble drugs is the use of cyclodextrin (CD)-based inclusion complexes. On the other hand, few studies have investigated how CD functions on the solubility of drugs in the presence of multiple drugs that interact with each other. In this study, we used indomethacin (IND) and diclofenac (DIC) as acidic drugs, famotidine (FAM) and cimetidine (CIM) as basic drugs, and imidazole (IMZ), histidine (HIS), and arginine (ARG) as compounds structurally similar to basic drugs. We attempted to clarify the effect of β-CD on the solubility change of each drug in the presence of multiple drugs. IND and DIC formed a eutectic mixture in the presence of CIM, IMZ, and ARG, which greatly increased the intrinsic solubility of the drugs as well as their affinity for β-CD. Furthermore, the addition of high concentrations of β-CD to the DIC-FAM combination, which causes a decrease in solubility due to the interaction, improved the solubility of FAM, which was decreased in the presence of DIC. These results indicate that β-CD synergistically improves the solubility of drugs in drug-drug combinations, where the solubility is improved, whereas it effectively improves the dissolution rate of drugs in situations where the solubility is reduced by drug-drug interactions, such as FAM-DIC. This indicates that β-CD can be used to improve the physicochemical properties of drugs, even when they are administered in combination with drugs that interact with each other.

Cyclodextrins Propolis Extract Encapsulation: Physicochemical Characterization, Toxicity Effect, and Application on Animal Sperm Cold Preservation

AbstractPropolis is composed of several bioactive compounds, which give it many beneficial biological effects. The use of cyclodextrins (CDs) is necessary when aiming to enhance the stability, absorption, and solubility of these substances in physiological media. The purpose of the present work is to study solubility diagrams of propolis extract of Melbou region (PEM) in the presence of CDs: α‐CD, β‐CD, and PM‐βCD, then to formulate an optimized preparation of the inclusion complex using a D‐optimal experimental design with three factors (ratio, ethanol solvent, and temperature). The optimal formulation is characterized by infrared spectroscopy (FTIR), X‐ray diffraction (XRD), and scanning electron microscopy (SEM). The cytotoxic and protective effects of the optimal formulation are evaluated in vitro against human red blood cells (RBCs) and beef sperm. The results show that PM‐βCD is more efficient, this is confirmed with an optimal formulation that obtained using 40 mL of solvent, a temperature of 40 °C with 1:1 stoichiometry. The cytotoxicity tests revealed that PEM and its inclusion complex are non‐toxic to RBCs and can maintain sperm conservation. It is concluded that PM‐βCD is more suitable to improve the solubility and stability of PEM constituents, and their non‐toxic effect has been approved.

Tuning the Solution Self-Assembly of a Peptide-PEG (Polyethylene Glycol) Conjugate with alpha-Cyclodextrin.

Cyclodextrins are saccharide ring molecules which act as host cavities that can encapsulate small guest molecules or thread polymer chains. We investigate the influence of alpha-cyclodextrin (αCD) on the aqueous solution self-assembly of a peptide-polymer conjugate YYKLVFF-PEG3K previously studied by our group [Castelletto et al., Polym. Chem., 2010, 1, 453-459]. This conjugate comprises a designed amyloid-forming peptide YYKLVFF that contains the KLVFF sequence from Amyloid β peptide, Aβ16-20, along with two aromatic tyrosine residues to enhance hydrophobicity as well as polyethylene glycol PEG with molar mass 3000 g mol-1. The conjugate self-assembles into β-sheet fibrils in aqueous solution. Here we show that complexation with αCD leads instead can produce free-floating nanosheets in aqueous solution (with a β-sheet structure). The transition from fibrils to nanosheets is driven by an increase in the number of αCD molecules threaded on the PEG chains, as determined by 1H NMR spectroscopy.These findings point to the use of cyclodextrin additives as a powerful means to tune the solution self-assembly in peptide-polymer conjugates and potentially other polymer/biomolecular hybrids.

Enhancing the Drug-Like Profile of a Potent Peptide PACE4 Inhibitor by the Formation of a Host-Guest Inclusion Complex with β-Cyclodextrin.

The enzyme PACE4 has been validated as a promising therapeutic target to expand the range of prostate cancer (PCa) treatments. In recent years, we have developed a potent peptidomimetic inhibitor, namely, compound C23 (Ac-(DLeu)LLLRVK-4-amidinobenzylamide). Like many peptides, C23 suffers from an unfavorable drug-like profile which, despite our efforts, has not yet benefited from the usual SAR studies. Hence, we turned our attention toward a novel formulation strategy, i.e., the use of cyclodextrins (CDs). CDs can benefit compounds through the formation of "host-guest" complexes, shielding the guest from degradation and enhancing biological survival. In this study, a series of βCD-C23 complexes have been generated and their properties evaluated, including potency toward the enzyme in vitro, a cell-based proliferation assay, and stability in plasma. As a result, a new βCD-formulated lead compound has been identified, which, in addition to being more soluble and more potent, also showed an improved stability profile.

Influence of the complex of chitosan-ß-cyclodextrin with levofloxacin on the wounds’ microflora and the Sturgeon’s colon intestine

The authors in the article presented the results of determining the effectiveness of using the chitosan-ß-cyclodextrin complex with levofloxacin in the healing of mechanical wounds of valuable commercial fish sturgeons and their feeding. The experiment was conducted based on the “Progressive biotechnologies in aquaculture” research laboratory of the Saratov State University of Genetics, Biotechnology and Engineering. N.I. Vavilov. The microflora of incised wounds and the large intestine of sturgeon fingerlings under the influence of fluoroquinolone, represented by levofloxacin based on cyclodextrin, included in the shell of high-molecular chitosan, was studied. The studied microbiological indicators were chosen to determine that changes in the total number of microorganisms show the nature of the course of the inflammatory/pathological process, which contributes to the development of microorganisms (including opportunistic pathogens) and lactic acid bacteria in the intestine. Therefore, they are essential physiological indicators of the formation of “ intestinal immunity. It was found that the use of cyclodextrin with levofloxacin in the treatment of incised wounds in sturgeons leads to a significant decrease in the total microbial number (TMC) on their surface (by 10 thousand times compared to the group without treatment). It has been shown that using cyclodextrin with levofloxacin in feeding sturgeons reduces the total microbial number in the large intestine. This complex is characterised by good solubility and bioavailability for fish. The future study results can be used in aquaculture to treat mechanical injuries received during transportation and sorting in the rearing process in fish.

The cholesterol depleting agent, (2-Hydroxypropyl)-ß-cyclodextrin, does not affect disease progression in SOD1G93A mice

Objective Previously, we demonstrated that Amyloid Precursor Protein (APP) contributes to pathology in the SOD1G93A mouse model of ALS and that genetic ablation of APP in SOD1G93A mice significantly improved multiple disease parameters, including muscle innervation and motor neuron survival. We also observed elevated levels of potentially neurotoxic Aß peptides that have been implicated in Alzheimer’s Disease (AD) pathogenesis, within motor neurons and astrocytes in SOD1G93A mice. More recently, it has been shown that blocking Aß production improves outcome measures in SOD1G93A mice. The cyclodextrin, (2-Hydroxypropyl)-ß-cyclodextrin (HP-β-CD), has previously been shown to deplete intraneuronal unesterified cholesterol, resulting in effective reduction of Aß production and amelioration of disease progression in mouse models of AD and Niemann Pick Type C (NPC) disease. Here, we tested whether HP-β-CD could also improve phenotypic progression in SOD1G93A mice. Methods Pre-symptomatic male SOD1G93A mice were randomly assigned to the following treatment groups: HP-β-CD (4000mg/kg, n = 9) or vehicle (saline; n = 10), delivered by weekly subcutaneous injection, commencing at 67 days of age. Longitudinal grip-strength and body mass analysis was performed until late-stage disease (120 days of age), followed by in vivo bilateral isometric muscle tension analysis of tibialis anterior (TA) and extensor digitorum longus (EDL) muscles. Results: HP-β-CD administration had no effect on body mass or grip-strength compared to vehicle treated SOD1G93A mice. Similarly, HP-β-CD treatment had no effect on muscle force, contractile properties or motor unit number estimates (MUNE) at late-stage disease in SOD1G93A mice. Conclusion This study shows that HP-β-CD does not confer any therapeutic benefit in SOD1G93A mice. However, the absence of detrimental effects is informative, given the common use of cyclodextrins as complexing agents for other pharmaceutical products, their standalone therapeutic potential and the emerging association between dyslipidaemia and ALS progression.

Innovative Delivery and Release Systems for Antioxidants and Other Active Substances in the Treatment of Cancer.

Cancer is one of the major diseases leading to death worldwide, and the fight against the disease is still challenging. Cancer diseases are usually associated with increased oxidative stress and the accumulation of reactive oxygen and nitrogen species as a result of metabolic alterations or signaling aberrations. While numerous antioxidants exhibit potential therapeutic properties, their clinical efficiency against cancer is limited and even unproven. Conventional anticancer antioxidants and drugs have, among others, the great disadvantage of low bioavailability, poor targeting efficiency, and serious side effects, constraining their use in the fight against diseases. Here, we review the rationale for and recent advances in potential delivery systems that could eventually be employed in clinical research on antioxidant therapy in cancer. We also review some of the various strategies aimed at enhancing the solubility of poorly water-soluble active drugs, including engineered delivery systems such as lipid-based, polymeric, and inorganic formulations. The use of cyclodextrins, micro- and nanoemulsions, and thermosensitive smart liposomes as useful systems for the delivery and release of poorly aqueous-soluble drugs, improving their bioactivity and stability, is also addressed. We also provide some details on their formulation processes and their use in a variety of medical applications. Finally, we briefly cover a case study specifically focused on the use of delivery systems to minimize oral cancer and associated dental problems.

Insights on cyclodextrin inclusion complexes in deep eutectic solvents:Water mixtures

The use of cyclodextrins (CDs) in combination with deep eutectic solvents (DESs) is nowadays an emerging and promising strategy for the solvation of hydrophobic compounds, such as aromas. This approach combines the solvation efficiency of the solvent bulk and the complexation ability of CDs. However, literature lacks information about the complexation mechanism in CDs in these non-conventional solvents. Hence, this study aims to elucidate such mechanism by investigating the complexation behavior and the binding ability of β-CD and α-CD towards verbenone and camphor, respectively, in choline chloride:urea DES:water (70:30 wt%) mixture. First, the formation constants (Kf) of the chosen model inclusion complexes were determined by static headspace-gas chromatography (SH-GC). Then, the formation of inclusion complexes was demonstrated by 1H 2D DOSY and 2D ROESY NMR studies. Finally, isothermal titration calorimetry (ITC) experiments were carried out, for the first time in a DES:water mixture, in order to evaluate the thermodynamic parameters of the inclusion phenomenon. Altogether, results proved the formation of stable inclusion complexes in the new non-conventional medium constituted of choline chloride:urea DES:water (70:30 wt%). Interestingly, the thermodynamic signatures and the stoichiometries of interactions were similar between water and choline chloride:urea DES:water (70:30 wt%). In particular, the present study of the α-CD/camphor system constitutes the first report of a 2:1 complex in a DES:water mixture.

Contemporary Review on Solubility Enhancement Techniques

The limited water solubility of pharmacoactive molecules hinders their ability to be used as pharmacological agents, yet the indispensability of a certain solubility parameter precludes any compromises. To overcome this challenge, various methods are employed in order to increase their bioavailability. Pharmaceutical molecules with lower solubility present an elevated risk of failure for drug development and innovation. Their solubility affects important processes such as pharmacokinetics, pharmacodynamics, distribution, protein binding, and absorption. As a result these parameters are greatly impacted by the dissolution rate of a particular molecule. Out of all pharmaceutical dosage forms, more than half are oral. For the drug molecule to reach its target site and be effective therapeutically, solubility and bioavailability must be taken into consideration. Unfortunately, during screening programs conducted by the pharmaceutical industry it became evident that nearly 40% of new chemical entities (NCEs) face various roadblocks when transitioning from formulation to development due to their poor solubility and bioavailability. The pharmaceutical industry is constantly confronted with the difficulty of improving drug bioavailability and solubility in formulations. This article covers a range of technological advancements to boost the solubility of insoluble drugs, such as complexation, emulsions and micelles production, microemulsion generation with cosolvents, polymeric micelle preparation methods, particle size decrease techniques, pharmaceutical salts application, prodrugs usage, solid-state alteration practices, soft gel technology implementation crystal engineering approaches and nanomorphology. Through this review, we will discuss a variety of more complex methods for improving solubility and bioavailability such as crystal engineering, micronization, solid dispersions, nano sizing, and use of cyclodextrins, solid lipid nanoparticles (SLNPs), colloidal drug delivery systems and drug conjugates. We'll also provide references to studies that have been conducted in connection with these topics.
 Keywords: Solubility, permeability, bioavailability, nano particles drug delivery systems, microemulsions, low water solubility