Development of inclusion complex based on cyclodextrin and oxazolidine derivative

Abstract Oxazolidine derivatives (OxD) have been described as third-line antibiotics and antitumoral agents. The inclusion complexes based on cyclodextrin could improve the solubility and bioavailability of these compounds. A novel synthetic OxD was used, and its inclusion complexes were based on 2-hydroxy-beta-cyclodextrin (2-HPßCD). We conducted an in silico study to evaluate the interaction capacity between OxD and 2-HPßCD. Characterization studies were performed through scanning electron microscopy (SEM), Fourier-transformed infrared (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), X-ray diffraction (XRD), and thermal analyses. A kinetic study of the OxD was performed, including a cytotoxicity assay using peripheral blood mononuclear cells (PBMCs). The maximum increment of solubility was obtained at 70 mM OxD using 400 mM 2-HPßCD. SEM analyses and FTIR spectra indicated the formation of inclusion complexes. 1H-NMR presented chemical shifts that indicated 1:1 stoichiometry. Different thermal behaviors were obtained. The pharmacokinetic profile showed a short release time. Pure OxD and its inclusion complex did not exhibit cytotoxicity in PBMCs. In silico studies provided a foremost insight into the interactions between OxD and 2-HPßCD, including a higher solubility in water and an average releasing profile without toxicity in normal cells

Overview of nanoparticulate strategies for solubility enhancement of poorly soluble drugs.

Poor aqueous solubility and poor bioavailability are major issues with many pharmaceutical industries. By some estimation, 70-90% drug candidates in development stage while up-to 40% of the marketed products are poorly soluble which leads to low bioavailability, reduced therapeutic effects and dosage escalation. That's why solubility is an important factor to consider during design and manufacturing of the pharmaceutical products. To-date, various strategies have been explored to tackle the issue of poor solubility. This review article focuses the updated overview of commonly used macro and nano drug delivery systems and techniques such as micronization, solid dispersion (SD), supercritical fluid (SCF), hydrotropy, co-solvency, micellar solubilization, cryogenic technique, inclusion complex formation-based techniques, nanosuspension, solid lipid nanoparticles, and nanogels/nanomatrices explored for solubility enhancement of poorly soluble drugs. Among various techniques, nanomatrices were found a promising and impeccable strategy for solubility enhancement of poorly soluble drugs. This article also describes the mechanism of action of each technique used in solubilization enhancement.

Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.

Utilization of Pectin from Okra as Binding Agent in Immediate Release Tablets.

Polymeric materials from plants continue to be of interest to pharmaceutical scientists as potential binders in immediate release tablets due to availability, sustainability, and constant supply to feed local pharmaceutical industries. Paracetamol tablet formulations were utilized in investigating the potential binding characteristics of pectin harnessed from various okra genotypes (PC1-PC5) in Ghana. The pectin yields from the different genotypes ranged from 6.12 to 18.84%w/w. The pH of extracted pectin ranged from 6.39 to 6.92, and it had good swelling indices and a low moisture content. Pectin extracted from all genotypes were evaluated as binders (10, 15, and 20%w/v) and compared to tragacanth BP. All formulated tablets (F1-F18) passed the weight uniformity, drug content, hardness, and friability tests. Based on their crushing strength, tablets prepared with pectin from the various genotypes were relatively harder (P ≤ 0.05) than tablets prepared with tragacanth BP. Tablets prepared with pectins as binders at 10%w/v and 15%w/v passed the disintegration and dissolution tests with the exception of PC4 at 15%w/v. Incorporation of pectin from all genotypes (excluding PC5) as a binder at concentrations above 15%w/v (F13, F16, F14, and F15) produced tablets which failed the disintegration test and showed poor dissolution profiles. Thus, pectin from these genotypes can be industrially commodified as binders in immediate release tablets using varying concentrations.

Design and Optimization of Cationic Nanocapsules for Topical Delivery of Tretinoin: Application of the Box-Behnken Design, In Vitro Evaluation, and Ex Vivo Skin Deposition Study.

Cationic nanocapsules represent a promising approach for topical delivery purposes. We elaborated on a novel formulation based on the cationic nanocapsules to enhance the pharmacodynamic efficacy, user compliance, and photostability of tretinoin (TTN). To achieve this goal, TTN nanocapsules were prepared by the nanoprecipitation method. In order to statistically optimize formulation variables, a Box-Behnken design, using Design-Expert software, was employed. Three independent variables were evaluated: total weight of the cationic acrylic polymer (X 1), oil volume (X 2), and TTN amount (X 3). The particle size and encapsulation efficiency percent (EE%) were selected as dependent variables. The optimal formulation demonstrated spherical morphology under scanning electron microscopy (SEM), optimum particle size of 116.3 nm, and high EE% of 83.2%. TTN-loaded nanocapsules improved photostability compared to its methanolic solution. The in vitro release study data showed that tretinoin was released in a sustained manner compared to the free drug. The ex vivo skin permeation study demonstrated that greater drug deposition into the epidermal region rather than the deep skin was observed with a gel containing TTN-loaded nanocapsules than that of drug solution, respectively. The skin irritation test revealed that the nanoencapsulation of the drug decreased its irritancy compared to the free drug. These results revealed the promising potential of cationic nanocapsules for topical delivery of tretinoin.

Impact of co-administered stabilizers on the biopharmaceutical performance of regorafenib amorphous solid dispersions.

Poor solubility of drug candidates is a well-known and thoroughly studied challenge in the development of oral dosage forms. One important approach to tackle this challenge is the formulation as an amorphous solid dispersion (ASD). To reach the desired biopharmaceutical improvement a high supersaturation has to be reached quickly and then be conserved long enough for absorption to take place. In the presented study, various formulations of regorafenib have been produced and characterized in biorelevant in-vitro experiments. Povidone-based formulations, which are equivalent to the marketed product Stivarga®, showed a fast drug release but limited stability and robustness after that. In contrast, HPMCAS-based formulations exhibited excellent stability of the supersaturated solution, but unacceptably slow drug release. The attempt to combine the desired attributes of both formulations by producing a ternary ASD failed. Only co-administration of HPMCAS as an external stabilizer to the rapidly releasing Povidone-based ASDs led to the desired dissolution profile and high robustness. This optimized formulation was tested in a pharmacokinetic animal model using Wistar rats. Despite the promising in-vitro results, the new formulation did not perform better in the animal model. No differences in AUC could be detected when compared to the conventional (marketed) formulation. These data represent to first in-vivo study of the new concept of external stabilization of ASDs. Subsequent in-vitro studies revealed that temporary exposure of the ASD to gastric medium had a significant and long-lasting effect on the dissolution performance and externally administered stabilizer could not prevent this sufficiently. By applying the co-administered HPMCAS as an enteric coating onto Stivarga tablets, a new bi-functional approach was realized. This approach achieved the desired tailoring of the dissolution profile and high robustness against gastric medium as well as against seeding.

In Silico Study, Physicochemical, and In Vitro Lipase Inhibitory Activity of α,ß-Amyrenone Inclusion Complexes with Cyclodextrins.

α,ß-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and ß-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.

Scientific Accuracy Matters.

The Solubility of Halothane in Blood and Tissue Homogenates. By Larson CP, Eger EI, Severinghaus JW. Anesthesiology 1962; 23:349-55. Measured samples of human and bovine blood, human hemoglobin, and tissue homogenates from human fat and both human and bovine liver, kidney, muscle, whole brain, and separated gray and white cortex were added to stoppered 2,000-ml Erlenmeyer flasks. To each flask, 0.1 ml of liquid halothane was added under negative pressure using a calibrated micropipette. After the flask was agitated for 2 to 4 h to achieve equilibrium between the gas and blood or tissue contents, a calibrated infrared halothane analyzer was used to measure the concentration of halothane vapor. Calculated partition coefficients ranged from 0.7 for water to 2.3 for blood and from 3.5 for human or bovine kidney to 6 for human whole brain or liver and 8 for human muscle. Human peritoneal fat had a value of 138. The human blood-gas partition coefficient of 2.3 as determined by this equilibration method was well below the previously published value of 3.6.

Molecular Dynamics Simulations and Experimental Results Provide Insight into Clinical Performance Differences between Sandimmune® and Neoral® Lipid-Based Formulations.

OBJECTIVE: Molecular dynamics (MD) simulations provide an in silico method to study the structure of lipid-based formulations (LBFs) and the incorporation of poorly water-soluble drugs within such formulations. In order to validate the ability of MD to effectively model the properties of LBFs, this work investigates the well-known cyclosporine A formulations, Sandimmune® and Neoral®. Sandimmune® exhibits poor dispersibility and its absorption from the gastrointestinal tract is enhanced when administered after food, whereas Neoral® disperses comparatively well and shows no food effect. METHODS: MD simulations were performed of both LBFs to investigate the differences observed in fasted and fed conditions. These conditions were also tested using an in vitro experimental model of dispersion and digestion. RESULTS: These MD simulations were able to show that the food effect observed for Sandimmune® can be explained by large changes in drug solubilization on addition of bile. In contrast, Neoral® is well dispersed in water or in simulated fasted conditions, and this dispersion is relatively unchanged on moving to fed conditions. These differences were confirmed using dispersion and digestion in vitro experimental model. CONCLUSIONS: The current data suggests that MD simulations are a potential method to model the fate of LBFs in the gastrointestinal tract, predict their dispersion and digestion, investigate behaviour of APIs within the formulations, and provide insights into the clinical performance of LBFs.

Development and Characterization of Novel Composite Films Based on Soy Protein Isolate and Oilseed Flours.

The possibility of using oilseed flours as a waste source for film-forming materials with a combination of soy protein isolate in preparation of edible films was evaluated. Physical, mechanical and barrier properties were determined as a function of the oilseed type: hemp, evening primrose, flax, pumpkin, sesame and sunflower. It was observed that the addition of oilseed flours increased the refraction and thus the opacity of the obtained films from 1.27 to 9.57 A mm-1. Depending on the type of flours used, the edible films took on various colors. Lightness (L*) was lowest for the evening primrose film (L* = 34.91) and highest for the soy protein film (L* = 91.84). Parameter a* was lowest for the sunflower film (a* = -5.13) and highest for the flax film (a* = 13.62). Edible films made of pumpkin seed flour had the highest value of the b* color parameter (b* = 34.40), while films made of evening primrose flour had the lowest value (b* = 1.35). All analyzed films had relatively low mechanical resistance, with tensile strength from 0.60 to 3.09 MPa. Films made of flour containing the highest amount of protein, pumpkin and sesame, had the highest water vapor permeability, 2.41 and 2.70 × 10-9 g·m-1 s-1 Pa-1, respectively. All the edible films obtained had high water swelling values from 131.10 to 362.16%, and the microstructure of the films changed after adding the flour, from homogeneous and smooth to rough. All blended soy protein isolate-oilseed flour films showed lower thermal stability which was better observed at the first and second stages of thermogravimetric analysis when degradation occurred at lower temperatures. The oilseed flours blended with soy protein isolate show the possibility of using them in the development of biodegradable films which can find practical application in the food industry.

Impact of Crystal Habit on the Dissolution Rate and In Vivo Pharmacokinetics of Sorafenib Tosylate.

The dissolution rate is the rate-limiting step for Biopharmaceutics Classification System (BCS) class II drugs to enhance their in vivo pharmacokinetic behaviors. There are some factors affecting the dissolution rate, such as polymorphism, particle size, and crystal habit. In this study, to improve the dissolution rate and enhance the in vivo pharmacokinetics of sorafenib tosylate (Sor-Tos), a BCS class II drug, two crystal habits of Sor-Tos were prepared. A plate-shaped crystal habit (ST-A) and a needle-shaped crystal habit (ST-B) were harvested by recrystallization from acetone (ACN) and n-butanol (BuOH), respectively. The surface chemistry of the two crystal habits was determined by powder X-ray diffraction (PXRD) data, molecular modeling, and face indexation analysis, and confirmed by X-ray photoelectron spectroscopy (XPS) data. The results showed that ST-B had a larger hydrophilic surface than ST-A, and subsequently a higher dissolution rate and a substantial enhancement of the in vivo pharmacokinetic performance of ST-B.

Mucoadhesive and mucus-penetrating interpolyelectrolyte complexes for nose-to-brain drug delivery.

Nasal administration offers a possibility of delivering drugs to the brain. In the present work, nasal drug delivery systems were designed based on cationic Eudragit® EPO (EPO) and anionic Eudragit® L100-55 (L100-55) methacrylate copolymers. Two types of nanocarriers were prepared using interpolyelectrolyte complexation between these polymers. The first type of nanoparticles was prepared by forming interpolyelectrolyte complexes between unmodified EPO and L100-55. The second type of nanoparticles was formed through the complexation between PEGylated L100-55 and EPO. For this purpose, PEGylated L100-55 was synthesized by chemical conjugation of L100-55 with O-(2-aminoethyl)polyethylene glycol. The mucoadhesive properties of these nanoparticles were evaluated ex vivo using sheep nasal mucosa. Nanoparticles based on EPO and L100-55 exhibited mucoadhesive properties towards nasal mucosa, whereas PEGylated nanoparticles were non-mucoadhesive hence displayed mucus-penetrating properties. Both types of nanoparticles were used to formulate haloperidol and their ability to deliver the drug to the brain was evaluated in rats in vivo.

Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals.

Poor aqueous solubility of active compounds is a major issue in today's drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.

Piroxicam Loading onto Mesoporous Silicas by Supercritical CO2 Impregnation.

Piroxicam (PRX) is a commonly prescribed nonsteroidal anti-inflammatory drug. Its efficacy, however, is partially limited by its low water solubility. In recent years, different studies have tackled this problem and have suggested delivering PRX through solid dispersions. All these strategies, however, involve the use of potentially harmful solvents for the loading procedure. Since piroxicam is soluble in supercritical CO2 (scCO2), the present study aims, for the first time, to adsorb PRX onto mesoporous silica using scCO2, which is known to be a safer and greener technique compared to the organic solvent-based ones. For comparison, PRX is also loaded by adsorption from solution and incipient wetness impregnation using ethanol as solvent. Two different commercial mesoporous silicas are used (SBA-15 and Grace Syloid® XDP), which differ in porosity order and surface silanol population. Physico-chemical analyses show that the most promising results are obtained through scCO2, which yields the amorphization of PRX, whereas some crystallization occurs in the case of adsorption from solution and IWI. The highest loading of PRX by scCO2 is obtained in SBA-15 (15 wt.%), where molecule distribution appears homogeneous, with very limited pore blocking.

Identification of Celecoxib-Targeted Proteins Using Label-Free Thermal Proteome Profiling on Rat Hippocampus.

Celecoxib, or Celebrex, a nonsteroidal anti-inflammatory drug, is one of the most common medicines for treating inflammatory diseases. Recently, it has been shown that celecoxib is associated with implications in complex diseases, such as Alzheimer disease and cancer as well as with cardiovascular risk assessment and toxicity, suggesting that celecoxib may affect multiple unknown targets. In this project, we detected targets of celecoxib within the nervous system using a label-free thermal proteome profiling method. First, proteins of the rat hippocampus were treated with multiple drug concentrations and temperatures. Next, we separated the soluble proteins from the denatured and sedimented total protein load by ultracentrifugation. Subsequently, the soluble proteins were analyzed by nano-liquid chromatography tandem mass spectrometry to determine the identity of the celecoxib-targeted proteins based on structural changes by thermal stability variation of targeted proteins toward higher solubility in the higher temperatures. In the analysis of the soluble protein extract at 67°C, 44 proteins were uniquely detected in drug-treated samples out of all 478 identified proteins at this temperature. Ras-associated binding protein 4a, 1 out of these 44 proteins, has previously been reported as one of the celecoxib off targets in the rat central nervous system. Furthermore, we provide more molecular details through biomedical enrichment analysis to explore the potential role of all detected proteins in the biologic systems. We show that the determined proteins play a role in the signaling pathways related to neurodegenerative disease-and cancer pathways. Finally, we fill out molecular supporting evidence for using celecoxib toward the drug-repurposing approach by exploring drug targets. SIGNIFICANCE STATEMENT: This study determined 44 off-target proteins of celecoxib, a nonsteroidal anti-inflammatory and one of the most common medicines for treating inflammatory diseases. It shows that these proteins play a role in the signaling pathways related to neurodegenerative disease and cancer pathways. Finally, the study provides molecular supporting evidence for using celecoxib toward the drug-repurposing approach by exploring drug targets.

Enrofloxacin/florfenicol loaded cyclodextrin metal-organic-framework for drug delivery and controlled release.

We presented an antibiotic-loaded γ-cyclodextrin metal-organic framework that delivered antibiotics suitable for the treatment of bacterial infections. The γ-cyclodextrin metal-organic framework was developed using γ-cyclodextrin and potassium ion via the ultrasonic method. The antibiotic (florfenicol and enrofloxacin) was primarily encapsulated into the pore structures of γ-CD-MOF, which allowed the sustained release of antibiotics over an extended period of time in vitro and in vivo. Notably, antibiotics-loaded γ-CD-MOF showed much superior activity against bacteria than free antibiotics (lower MIC value) and displayed better long-lasting activity (longer antibacterial time). The antibiotics-loaded γ-CD-MOF showed nontoxic and perfect biocompatibility to mammalian cells and tissues both in vitro and in vivo. These materials thus represent a novel drug-delivery device suitable for antibiotic therapy. This research is of great significance for reducing the generation of bacterial resistance and providing new ideas for the application of γ-CD-MOF.

Physicochemical and bioactive properties of a high ß-glucan barley variety 'Betaone' affected by germination processing.

This study was conducted to investigate the effects of germination on the bioactive phytochemicals in the barley variety 'Betaone', which has high ß-glucan content. Betaone barley seeds were germinated for 24, 48, 72, and 96 h at 25 °C in a growth chamber. As the germination period progressed, crude protein, crude fat, and crude ash levels increased, while starch content decreased. ß-Glucan content significantly decreased during the germination period. However, after 96 h of germination, it was still 4.31%, which is similar to the amount found in ordinary barley varieties. The α- and ß-amylase activities in Betaone barley increased, thereby significantly decreasing pasting viscosities (p ≤ 0.05), as germination progressed. The water absorption index increased in the early germination stage, subsequently decreasing as germination progressed. While the water solubility index fell in the first stage of germination, it subsequently increased as germination progressed. Oil absorption decreased as germination progressed. Bioactive compounds, in particular the total phenolic (122.84-322.67 µg/g), total flavonoid (32.20-124.09 µg/g), and GABA content (176.94-212.64 µg/g), increased as germination progressed. The antioxidative properties mainly DPPH and ABTS radical scavenging activity also increased during the germination period. Therefore, these findings could be a useful method for improving new products with enhanced bioactive phytochemicals.

Oral Delivery of Gambogenic Acid by Functional Polydopamine Nanoparticles for Targeted Tumor Therapy.

To enhance the water solubility, oral bioavailability, and tumor targeting of gambogenic acid (GNA), polydopamine nanoparticles (PDA NPs) were prepared to encapsulate and stabilize GNA surface modified by folic acid (FA) and then coated with sodium alginate (GNA@PDA-FA SA NPs) to achieve an antitumor effect by oral administration. GNA@PDA-FA SA NPs exhibited in vitro pH-sensitive release behavior. In vitro cell studies manifested that GNA@PDA-FA NPs had higher cytotoxicity to 4T1 cells compared with raw GNA (IC50 = 2.58 µM vs 7.57 µM). After being modified with FA, GNA@PDA-FA NPs were taken up easily by 4T1 cells. In vivo studies demonstrated that the area under the curve (AUC0→∞) of the plasma drug concentration-time of GNA@PDA-FA SA NPs was 2.97-fold higher than that of raw GNA, along with improving drug distribution in the liver, lung, and kidney tissues. In vivo anti-tumor experiments, GNA@PDA-FA SA NPs significantly inhibited the growth of breast tumors in the 4T1 xenograft breast cancer model via oral administration without obvious toxicity on major organs. Our studies indicated that the GNA@PDA-FA SA NPs modified with FA and coated with SA were a promising drug delivery system for targeting tumor therapy via oral administration.

Combined Effect of the Preparation Method and Compression on the Physical Stability and Dissolution Behavior of Melt-Quenched Amorphous Celecoxib.

In an earlier investigation, amorphous celecoxib was shown to be sensitive to compression-induced destabilization. This was established by evaluating the physical stability of uncompressed/compressed phases in the supercooled state (Be̅rzins . Mol. Pharmaceutics, 2019, 16(8), 3678-3686). In this study, we investigated the ramifications of compression-induced destabilization in the glassy state as well as the impact of compression on the dissolution behavior. Slow and fast melt-quenched celecoxib disks were compressed with a range of compression pressures (125-500 MPa) and dwell times (0-60 s). These were then monitored for crystallization using low-frequency Raman spectroscopy when kept under dry (∼20 °C; <5% RH) and humid (∼20 °C; 97% RH) storage conditions. Faster crystallization was observed from the samples, which were compressed using more severe compression parameters. Furthermore, crystallization was also affected by the cooling rate used to form the amorphous phases; slow melt-quenched samples exhibited higher sensitivity to compression-induced destabilization. The behavior of the melt-quench disks, subjected to different compression conditions, was continuously monitored during dissolution using low-frequency Raman and UV/vis for the solid-state form and dissolution properties, respectively. Surprisingly the compressed samples exhibited higher apparent dissolution (i.e., higher area under the dissolution curve and initial celecoxib concentration in solution) than the uncompressed samples; however, this is attributed to biaxial fracturing throughout the compressed compacts yielding a greater effective surface area. Differences between the slow and fast melt quenched samples showed some trends similar to those observed for their storage stability.

Effect of Polymer Species on Maximum Aqueous Phase Supersaturation Revealed by Quantitative Nuclear Magnetic Resonance Spectroscopy.

The polymer used in an amorphous solid dispersion (ASD) formulation impacts the maximum achievable drug supersaturation. Herein, the effect of dissolved polymer on drug concentration in the aqueous phase when a drug-rich phase was generated by liquid-liquid phase separation (LLPS) was investigated for different polymers at various concentrations of drug and polymer. Solution nuclear magnetic resonance (NMR) spectroscopy revealed that polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinyl acetate (PVP-VA), and hypromellose (HPMC) distributed into the ibuprofen (IBP)-rich phase formed by LLPS when the amorphous solubility of IBP was exceeded. The amount of polymer in the drug-rich phase increased for higher-molecular-weight grades of PVP and HPMC. Moreover, PVP-VA showed a greater extent of distribution into the IBP-rich phase compared to PVP, and this is attributed to its reduced hydrophilicity resulting from the incorporation of vinyl acetate monomers. Direct quantification by NMR measurements indicated that the IBP concentration in the aqueous phase decreased as the amount of polymer in the IBP-rich phase increased. This can be attributed to a reduction of the chemical potential of IBP in the IBP-rich phase. The reduction in dissolved IBP concentration was greater for the IBP/PVP-VA system compared to the IBP/HPMC system, as a result of more extensive drug-polymer interactions in the former system. The present study highlights the impact of polymer selection on the attainable supersaturation of the drug and the factors that need to be considered in the formulation of ASDs to obtain optimized in vivo performance.