Host-Guest Interaction Study of Olmesartan Medoxomil with ß-Cyclodextrin Derivatives.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated ß-cyclodextrin (RM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-ß-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-ß-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

Host-Guest Complexes of Flavanone and 4'-Chloroflavanone with Naturals and Modified Cyclodextrin: A Calorimetric and Spectroscopy Investigations.

The aim of the research was to investigate and compare the interaction between flavanones (flavanone, 4-chloro-flavanone) with potential anticancer activity and selected cyclodextrins. Measurements were made using calorimetric (ITC, DSC) and spectrophotometric (UV-Vis spectroscopy, FT-IR, 1H NMR) methods. The increase in the solubility in aqueous medium caused by the complexation process was determined by the Higuchi-Connors method. As a result of the study, the stoichiometry and thermodynamics of the complexation reaction were determined. The formation of stable inclusion complexes at a 1:1 M ratio between flavanone and 4-chloroflavanone and the cyclodextrins selected for research was also confirmed.

An innovative carrier for the formulation of amorphous solid dispersion by hot-melt extrusion with no further downstream processes: a case study with indomethacin.

The aim of this work was to study the possibility to use SepitrapTM as a carrier for the formulation of amorphous solid dispersions by HME (hot melt extrusion) processing aiming solubility enhancement of poorly water-soluble drugs. SepitrapTM is a microencapsulated powder solubilizer designed to simplify the manufacture of drugs in oral solid forms, not yet tested for this purpose. The performance of SepitrapTM was evaluated in HME processing for amorphous solid dispersions of poorly-water soluble drugs with indomethacin as a model drug. The study was conducted using a twin-screw extruder, two compositions of SepitrapTM and different loads of indomethacin, demonstrating that SepitrapTM could represent a new range of carriers for amorphous solid dispersions for HME processing, reducing necessary downstream steps such as grinding.

An In Vitro Model for Cocrystal Dissolution with Simultaneous Surface and Bulk Precipitation.

Cocrystals can be promising means of overcoming the poor aqueous solubility of many drugs. However, precipitation of the stable drug at the cocrystal surface or in the bulk medium is often provoked during cocrystal dissolution due to high drug supersaturation, which prevents sustaining high drug concentrations for enhanced bioavailability. There is a need for predictive in vitro models that can accurately describe this cocrystal dissolution-supersaturation-precipitation (DSP) process to aid drug development and formulation design. Consideration of surface precipitation is often essential for such models given the strong impact of surface precipitation on the drug concentration during cocrystal dissolution. However, DSP models that can explicitly account for the effect of surface precipitation are currently lacking. This work presents a population balance-based model to describe in vitro cocrystal DSP behavior, which accounts for cocrystal dissolution, surface precipitation, and bulk precipitation. Dissolution experiments with carbamazepine-succinic acid cocrystals are conducted for model development and validation. The developed model captures all of the principal experimental trends and predicts the dose-dependent DSP behavior outside the regression data set with reasonable accuracy. The results show that surface precipitation is an essential component of the model. Finally, the new model is integrated with numerical optimization to illustrate how it can be used to identify an optimal dose, particle size, and amount of predissolved coformer.

Effect of Buffer pH and Concentration on the Dissolution Rates of Sodium Indomethacin-Copovidone and Indomethacin-Copovidone Amorphous Solid Dispersions.

The incorporation of counterions into amorphous solid dispersions (ASDs) has been proven to be effective for improving the dissolution rates of ionizable drugs in ASDs. In this work, the effect of dissolution buffer pH and concentration on the dissolution rate of indomethacin-copovidone 40:60 (IMC-PVPVA, w/w) ASD with or without incorporated sodium hydroxide (NaOH) was studied by surface area-normalized dissolution to provide further mechanistic understanding of this phenomenon. Buffer pH from 4.7 to 7.2 and concentration from 20 to 100 mM at pH 5.5 were investigated. As the buffer pH decreased, the IMC dissolution rate from both ASDs decreased. Compared to IMC-PVPVA ASD, the dissolution rate decrease from IMCNa-PVPVA ASD was more resistant to the decrease of buffer pH. In contrast, while buffer concentration had a negligible impact on the IMC dissolution rate from IMC-PVPVA ASD, the increase of buffer concentration significantly reduced the IMC dissolution rate from IMCNa-PVPVA ASD. Surrogate evaluation of microenvironment pH modification by the dissolution of IMCNa-PVPVA ASD demonstrated the successful elevation of buffer microenvironment pH and the suppression of such pH elevation by the increase of buffer concentration. These results are consistent with the hypothesis that the dissolution rate enhancement by the incorporation of counterions originates from the enhanced drug solubility by ionization and the modification of diffusion layer pH in favor of drug dissolution. At the studied drug loading (∼40%), relatively congruent release between IMC and PVPVA was observed when IMC was ionized in ASD or in solution, highlighting the importance of studying the ionization effect on the congruent release of ASDs, especially when drug ionization is expected in vivo. Overall, this work further supports the application of incorporating counterions into ASDs for improving the dissolution rates of ionizable drugs when enabling formulation development is needed.

A review of transglycosylated compounds as food additives to enhance the solubility and oral absorption of hydrophobic compounds in nutraceuticals and pharmaceuticals.

Transglycosylation has been used to modify the physicochemical properties of original compounds. As a result, transglycosylated compounds can form molecular aggregates in size ranges of a few nanometers in an aqueous medium when their concentrations exceed a specific level. Incorporating these hydrophobic compounds has been observed to enhance the solubility of hydrophobic compounds into aggregate structures. Thus, this review introduces four transglycosylated compounds as food additives that can enhance the solubility and oral absorption of hydrophobic compounds. Here, transglycosylated hesperidin, transglycosylated rutin, transglycosylated naringin, and transglycosylated stevia are the focus as representative substances. Significantly, we observed that amorphous formations containing hydrophobic compounds with transglycosylated compounds improved solubility and oral absorption compared to untreated hydrophobic compounds. Moreover, combining transglycosylated compounds with hydrophilic polymers or surfactants enhanced the solubilizing effects on hydrophobic compounds. Furthermore, the enhanced solubility of hydrophobic compounds improved their oral absorption. Transglycosylated compounds also influenced nanoparticle preparation of hydrophobic compounds as a dispersant. This study demonstrated the benefits of transglycosylated compounds in developing supplements and nutraceuticals of hydrophobic compounds with poor aqueous solubility.

Sustainable, economical and rapid treatment of multiple lung diseases using therapeutic potential of curcumin nanoparticles.

The study was designed to prepare pure curcumin nanoparticles in rapid and simple way for target specific drug delivery to kill bacteria lying deep down within the alveoli of lungs via inhaler. Three different methods including evaporation precipitation of nanosuspension (ENP), solid dispersion (SD) and anti-solvent precipitation (ASP) were selected to prepare nanocurcumin in pure form in very simple way. This was done to compare their efficiency in terms of particle size obtained and water solubility and bacterial toxicity of as prepared curcumin nanoparticles. In this comparative study, curcumin NPs obtained from three different methods having particles size 65.3 nm, 98.7 nm and 47.4 nm respectively. The NPs were characterized using various techniques like SEM, XRD, UV-Visible and FTIR for their particle size determination and solubility evaluation. These particles were screened off against five bacterial strains causing lung diseases. AB3 prepared by ASP method, being smallest sized nanostructures, showed maximum solubility in water. These nanoparticles can be used as drug directly via inhaler to the target area without using any support or nano-carrier. In this way minimum dose formulation is required to target bacteria.

Modification and Solubility Enhancement of Rice Protein and Its Application in Food Processing: A Review.

Rice protein is a high-quality plant-based protein source that is gluten-free, with high biological value and low allergenicity. However, the low solubility of rice protein not only affects its functional properties such as emulsification, gelling, and water-holding capacity but also greatly limits its applications in the food industry. Therefore, it is crucial to modify and improve the solubility of rice protein. In summary, this article discusses the underlying causes of the low solubility of rice protein, including the presence of high contents of hydrophobic amino acid residues, disulfide bonds, and intermolecular hydrogen bonds. Additionally, it covers the shortcomings of traditional modification methods and the latest compound improvement methods, compares various modification methods, and puts forward the best sustainable, economical, and environmentally friendly method. Finally, this article lists the uses of modified rice protein in dairy, meat, and baked goods, providing a reference for the extensive application of rice protein in the food industry.

Solid amorphous formulations for enhancing solubility and inhibiting Erlotinib crystallization during gastric-to-intestinal transfer.

The objective of this study was to improve the solubility and inhibit the crystallisation during the gastric-to-intestinal transfer of Erlotinib (ERL), a small molecule kinase inhibitor (smKI) compound class, which is classified as class II drug in the Biopharmaceutical Classification System (BCS). A screening approach combining different parameters (solubility in aqueous media, inhibitory effect of drug crystallisation from supersaturated drug solutions) was applied to selected polymers for the development of solid amorphous dispersions of ERL. ERL solid amorphous dispersions formulations were then prepared with 3 different polymers (Soluplus®, HPMC-AS-L, HPMC-AS-H) at a fixed drug: polymer ratio (1:4) by two different production methods (spray drying and hot melt extrusion). The spray-dried particles and cryo-milled extrudates were characterized by thermal properties, shape and particle size, solubility and dissolution behavior in aqueous media. The influence of the manufacturing process on these solid characteristics was also identified during this study. Based on the obtained results, it is concluded that the cryo-milled extrudates of HPMC-AS-L displayed better performance (enhanced solubility, reduced ERL crystallization during the simulated gastric-to-intestinal transfer) and represents a promising amorphous solid dispersion formulation for oral administration of ERL.

Emerging Applications of Hydroxypropyl Methylcellulose Acetate Succinate: Different Aspects in Drug Delivery and Its Commercial Potential.

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has multi-disciplinary applications spanning across the development of drug delivery systems, in 3D printing, and in tissue engineering, etc. HPMCAS helps in maintaining the drug in a super-saturated condition by inhibiting its precipitation, thereby increasing the rate and extent of dissolution in the aqueous media. HPMCAS has several distinctive characteristics, such as being amphiphilic in nature, having an ionization pH, and a succinyl and acetyl substitution ratio, all of which are beneficial while developing formulations. This review provides insights regarding the various types of formulations being developed using HPMCAS, including amorphous solid dispersion (ASD), amorphous nanoparticles, dry coating, and 3D printing, along with their applicability in drug delivery and biomedical fields. Furthermore, HPMCAS, compared with other carbohydrate polymers, shows several benefits in drug delivery, including proficiency in imparting stable ASD with a high dissolution rate, being easily processable, and enhancing bioavailability. The various commercially available formulations, regulatory considerations, and key patents containing the HPMCAS have been discussed in this review.

Nanofibers of Glycyrrhizin/Hydroxypropyl-ß-Cyclodextrin Inclusion Complex: Enhanced Solubility Profile and Anti-inflammatory Effect of Glycyrrhizin.

Despite having a wide range of therapeutic advantages, glycyrrhizin (GL) has few commercial applications due to its poor aqueous solubility. In this study, we combined the benefits of hydroxypropyl ß-cyclodextrin (HP-ßCD) supramolecular inclusion complexes and electrospun nanofibers to improve the solubility and therapeutic potential of GL. A molecular inclusion complex containing GL and HP-ßCD was prepared by lyophilization at a 1:2 molar ratio. GL and hydroxypropyl ß-cyclodextrin inclusion complexes were also incorporated into hyaluronic acid (HA) nanofibers. Prepared NF was analyzed for physical, chemical, thermal, and pharmaceutical properties. Additionally, a rat model of carrageenan-induced hind paw edema and macrophage cell lines was used to evaluate the anti-inflammatory activity of GL-HP-ßCD NF. The DSC and XRD analyses clearly showed the amorphous state of GL in nanofibers. In comparison to pure GL, GL-HP-ßCD NF displayed improved release (46.6 ± 2.16% in 5 min) and dissolution profiles (water dissolvability ≤ 6 s). Phase solubility results showed a four-fold increase in GL solubility in GL-HP-ßCD NF. In vitro experiments on cell lines showed that inflammatory markers like IL-1ß, TNF-α, and IL-6 were significantly lower in GL-HP-ßCD NF compared to pure GL (p < 0.01 and p < 0.05). According to in vivo results, the prepared nanofiber exhibits a better anti-inflammatory effect than pure GL (63.4% inhibition vs 53.7% inhibition). The findings presented here suggested that GL-HP-ßCD NF could serve as a useful strategy for improving the therapeutic effects of GL.

In Silico Screening as a Tool to Prepare Drug-Drug Cocrystals of Ibrutinib-Ketoconazole: a Strategy to Enhance Their Solubility Profiles and Oral Bioavailability.

Ibrutinib (IBR) is a biopharmaceutical classification system (BCS) class II drug and an irreversible Bruton's tyrosine kinase (BTK) inhibitor. IBR has an extremely low oral bioavailability due to the activity of the CYP3A4 enzyme. The current intention of the research was to enhance solubility followed by oral bioavailability of IBR using the hot melt extrusion (HME) technique by formulating drug-drug cocrystals (DDCs). Ketoconazole (KET) is an active CYP3A4 inhibitor and was selected based on computational studies and solubility parameter prediction. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM) evaluations were employed for estimating the formation of IBR-KET DDCs. The IBR-KET DDC system was discovered to have a hydrogen bond (H-bond) and π-π-stacking interactions, in accordance with the computational results. Further, IBR-KET DDCs showed enhanced solubility, stability, powder dissolution, in vitro release, and flow properties. Furthermore, IBR-KET-DDCs were associated with enhanced cytotoxic activity in K562-CCL-243 cancer cell lines when compared with IBR and KET alone. In vivo pharmacokinetic studies have shown an enhanced oral bioavailability of up to 4.30 folds of IBR and 2.31 folds of KET through IBR-KET-DDCs compared to that of the IBR and KET suspension alone. Thus, the prepared IBR-KET-DDCs using the HME technique stand as a favorable drug delivery system that augments the solubility and oral bioavailability of IBR along with KET.

Solubility enhancement of extract of Lagenaria siceraria by development of Phospholipon® 90 H modulated phospholipid complex employing Box-Behnken design.

In the past decade, plant sterols gained more attention due to their significant therapeutic activity, but their poor solubility and low bioavailability limited their use. Here, we developed and optimized phospholipon® 90H modulated phospholipid (PmP) complex of ethanolic extract of Lagenaria siceraria (EELs) by solvent evaporation using Box-Behnken Design. The optimized PmP complex was then evaluated physico-chemically and functionally by particle size and zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) and apparent solubility studies. Phospholipon® 90 H (1-Oleoyl-2-palmitoyl-phosphatidylcholine) consists of 85% stearic acid and about 15% palmitic acid., with N,N,N-trimethylethanolammonium cation (choline) as a polar head attached to phosphate group acting as an anion, which forms a weaker intermolecular hydrogen bonding with the third hydroxyl group of isolated sterols. This interaction causes the sterols to get incorporated into the phospholipid at the molecular level. Thereby it leads to the formation of PmP-complex, which enhanced chemical stability with improved solubility. The apparent solubility study demonstrated more than 26-fold increase in aqueous solubility of EELs after forming PmP-complex. This complex with enhanced solubility may be formulated into various pharmaceutical dosage forms, and further pharmacological studies may solve the biopharmaceutical aspects related to therapeutic efficacy.

Optimization and characterization of self-nanoemulsifying drug delivery system of iloperidone using box-behnken design and desirability function.

PURPOSE: Iloperidone (IP) is an antipsychotic drug which belongs to Biopharmaceutical Classification System (BCS) II exhibiting poor aqueous solubility. The current investigation explores the possibility of enhancement of solubility and dissolution characteristics of IP by formulation of liquid self-nano emulsifying drug delivery system (L-SNEDDS) utilizing Box-Behnken Design (BBD) and desirability function. METHODS: The oils, surfactants and co-surfactants used in the study were selected based on solubility of the drug and their emulsification ability. Optimization of the formulation was performed using BBD by employing four response variables such as globule size (nm), percentage transmittance (%), self-emulsification time (sec) and percent drug released in 15min. 2D contour plots and 3D response surface plots were constructed using Design Expert software. RESULTS: The developed optimal L-SNEDDS of IP through BBD approach resulted in improvement of solubility and dissolution rate as compared with the pure drug. Based on desirability function, optimized formulation was prepared and was assessed for response variables (globule size, percentage transmittance, self-emulsification time and percent drug dissolved in 15min). The characterization studies revealed droplet size to be 21.80±2.41nm, 99.584±0.65% transmittance, 24.43±2.12sec emulsification time and 95.31±1.57% cumulative drug release in 15min. CONCLUSION: The results conclude the potentiality of prepared L-SNEDDS in improving solubility and dissolution rate of IP.

Structural modification aimed for improving solubility of lead compounds in early phase drug discovery.

Many lead compounds fail to reach clinical trials despite being potent because of low bioavailability attributed to their insufficient solubility making solubility a primary and crucial factor in early phase drug discovery. Solubility improvement of poorly soluble lead compounds without losing potency is a challenging task for the medicinal chemist in a drug discovery setup. Solubility is an important factor not only to dissipate or liquefy a substance but also to attain an optimal concentration of drug in systemic circulation required for the desired therapeutic effect. It has been estimated that more than forty percent of newly developed molecules are practically insoluble in water. Molecules with poor solubility not only cause difficulty for in vitro and in vivo assays but also add significant burdens to drug development in the form of longer time taken and increased cost to optimize the solubility. To tackle this problem, different techniques are being used such as physical, chemical, and miscellaneous methods to enhance solubility. Among them, the medicinal chemistry approach focussed on structural modification is a versatile and unique approach in way that it can also improve other pharmacokinetic/physicochemical parameters simultaneously. In this review, we have begun with brief introduction of solubility and its role followed by recent successful examples of different structural modification tactics reported in the literature including synthesis of prodrugs, hydrophilic and ionizable group insertion, addition & removal of hydrogen bonding, bioisosterism, disruption of molecular symmetry and planarity. Moreover, we have included a section on the obstacles in the solubility optimization and also summarised different in silico tools with potential application in solubility prediction. Overall, this review encompasses various successfully used solubility optimization examples using structure modification.

A Review of Coformer Utilization in Multicomponent Crystal Formation.

Most recently discovered active pharmaceutical molecules and market-approved medicines are poorly soluble in water, resulting in limited drug bioavailability and therapeutic effectiveness. The application of coformers in a multicomponent crystal method is one possible strategy to modulate a drug's solubility. A multicomponent crystal is a solid phase formed when several molecules of different substances crystallize in a crystal lattice with a certain stoichiometric ratio. The goal of this review paper is to comprehensively describe the application of coformers in the formation of multicomponent crystals as solutions for pharmaceutically active ingredients with limited solubility. Owing to their benefits including improved physicochemical profile of pharmaceutically active ingredients, multicomponent crystal methods are predicted to become increasingly prevalent in the development of active drug ingredients in the future.

Pharmaceutical Co-crystal of Antiviral Agent Efavirenz with Nicotinamide for the Enhancement of Solubility, Physicochemical Stability, and Oral Bioavailability.

The present research work attempted to improve the oral bioavailability of the antiviral drug Efavirenz (EFV) using a pharmaceutical cocrystallization technique. EFV comes under BCS-II and has extremely low water solubility, and results in low oral bioavailability. EFV and nicotinamide (NICO) were selected in a (1:1) stoichiometric ratio and efavirenz nicotinamide cocrystal (ENCOC) was prepared through the liquid-assisted grinding method (LAG). The confirmation of the formation of a new solid phase was done through spectroscopic techniques like Fourier transmission infrared (FTIR), Raman, and 13C solid-state nuclear magnetic resonance (13C ssNMR). Thermal techniques like differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and hot stage microscopy (HSM) illustrated the thermal behavior and melting patterns of ENCOC, EFV, and NICO. The X-ray powder diffraction (XRPD) confirms the formation of a new crystalline phase in ENCOC. The Morphology was determined through scanning electron microscopy (FESEM). The results of saturated solubility studies and in vitro drug release studies exhibited 8.9-fold enhancement in solubility and 2.56-fold enhancement in percentage cumulative drug release. The percentage drug content of ENCOC was found higher than 97% and cocrystal exhibits excellent accelerated stability. The oral bioavailability of EFV (Cmax, 799.08 ng/mL) exhibits significant enhancement after cocrystallization (Cmax, 5597.09 ng/mL) than EFV and Efcure®-200 tablet (2896.21 ng/mL). The current work investigates the scalable and cost-effective method for enhancement of physicochemical stability, solubility, and oral bioavailability of an antiviral agent EFV.

Drug Release and Nanodroplet Formation from Amorphous Solid Dispersions: Insight into the Roles of Drug Physicochemical Properties and Polymer Selection.

Dissolution of amorphous solid dispersions (ASD) can lead to the formation of amorphous drug-rich nano species (nanodroplets) via liquid-liquid phase separation or glass-liquid phase separation when the drug concentration exceeds the amorphous solubility. These nanodroplets have been shown to be beneficial for ASD performance both in vitro and in vivo. Thus, understanding the generation and stability of nanodroplets from ASD formulations is important. In this study, the impacts of polymer selection and active pharmaceutical ingredient (API) physicochemical properties (wet glass transition temperature (Tg) and log P) on nanodroplet release were studied. Six APIs with different physicochemical properties were formulated as ASDs with two polymers, polyvinylpyrrolidone/vinyl acetate (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS). Their release performance was evaluated using both powder and surface normalized dissolution of compacts. In general, HPMCAS-based dispersions resulted in higher drug release compared to PVPVA-based dispersions. The two polymers also exhibited different trends in nanodroplet formation as a function of drug loading (DL). PVPVA ASDs exhibited a "falling-off-the-cliff" effect, with a dramatic decline in release performance with a small increase in drug loading, while HPMCAS ASDs exhibited a negative "slope" in the release rate as a function of drug loading. For both polymers, low Tg compounds achieved higher levels of nanodroplet formation compared to high Tg compounds. The nanodroplets generated from ASD dissolution were also monitored with dynamic light scattering, and HPMCAS was found to be more effective at stabilizing nanodroplets against size increase. Insights from this study may be used to guide formulation design and selection of excipients based on API physicochemical properties.

Nanostructure and Molecular-Level Characterization of Aminoalkyl Methacrylate Copolymer and the Impact on Drug Solubilization Ability.

The effects of pH changes and saccharin (SAC) addition on the nanostructure and mobility of the cationic aminoalkyl methacrylate copolymer Eudragit E PO (EUD-E) and its drug solubilization ability were investigated. Small-angle X-ray scattering performed using synchrotron radiation and atomic force microscopy showed that the EUD-E nanostructure, which has a size of approximately several nanometers, changed from a random coil structure at low pH (pH 4.0-5.0) to a partially folded structure at high pH (pH 5.5-6.5). The EUD-E also formed a partially folded structure in a wide pH range of 4.5-6.5 when SAC was present, and the coil-to-globule transition was moderate with pH increase, compared with that when SAC was absent. The equilibrium solubility of the neutral drug naringenin (NAR) was enhanced in the EUD-E solution and further increased as the pH increased. The enlargement of the hydrophobic region of EUD-E in association with the coil-to-globule transition led to efficient solubilization of NAR. The interaction with SAC enhanced the mobility of the EUD-E chains in the hydrophobic region of EUD-E, resulting in changes in the drug-solubilizing ability. 1H high-resolution magic-angle spinning NMR measurements revealed that the solubilized NAR in the partially folded structure of EUD-E showed higher molecular mobility in the presence of SAC than in the absence of SAC. This study highlighted that solution pH and the presence of SAC significantly changed the drug solubilization ability of EUD-E, followed by changes in the EUD-E nanostructure, including its hydrophobic region.

Synthesis of PEG-4000-co-poly (AMPS) nanogels by cross-linking polymerization as highly responsive networks for enhancement in meloxicam solubility.

Poor solubility is an ongoing issue and the graph of poorly soluble drugs has increased markedly which critically affect their dissolution, bioavailability, and clinical effects. This common issue needs to be addressed, for this purpose a series of polyethylene glycol (PEG-4000) based nanogels were developed by free radical polymerization technique to enhance the solubility, dissolution, and bioavailability of poorly soluble drug meloxicam (MLX), as improved solubility is the significant application of nanosystems. Developed nanogels formulations were characterized by FTIR, XRD, SEM, zeta sizer, percent equilibrium swelling, drug loaded content (DLC), drug entrapment efficiency (DEE), solubility studies, and in vitro dissolution studies. Furthermore, cytotoxicity studies were conducted in order to determine the bio-compatibility of the nanogels drug delivery system to biological environment. Nanogels particle size was found to be 156.19 ± 09.33 d.nm. Solubility study confirmed that the solubility of poorly soluble drug MLX was significantly enhanced up to 36 folds as compared to reference product (Mobic®). The toxicity study conducted on rabbits and MTT assay endorsed the safety of the developed nanogels formulations to the biological system.