Amorphous Solubility Advantage: Theoretical Considerations, Experimental Methods, and Contemporary Relevance.

Twenty-five years ago, Hancock and Parks asked a provocative question: "what is the true solubility advantage for amorphous pharmaceuticals?" Difficulties in determining the amorphous solubility have since been overcome due to significant advances in theoretical understanding and experimental methods. The amorphous solubility is now understood to be the concentration after the drug undergoes liquid-liquid or liquid-glass phase separation, forming a water-saturated drug-rich phase in metastable equilibrium with an aqueous phase containing molecularly dissolved drug. While crystalline solubility is an essential parameter impacting the absorption of crystalline drug formulations, amorphous solubility is a vital factor for considering absorption from supersaturating formulations. However, the amorphous solubility of drugs is complex, especially in the presence of formulation additives and gastrointestinal components, and concentration-based measurements may not indicate the maximum drug thermodynamic activity. This review discusses the concept of the amorphous solubility advantage, including a historical perspective, theoretical considerations, experimental methods for amorphous solubility measurement, and the contribution of supersaturation and amorphous solubility to drug absorption. Leveraging amorphous solubility and understanding the associated physicochemical principles can lead to more effective development strategies for poorly water-soluble drugs, ultimately benefiting therapeutic outcomes.

Enhanced bioavailability and efficacy in antimalarial treatment through QbD approach enteric encased inclusion delivery.

Aim: In this study, we aimed to prepare enteric encapsulated spheroids containing inclusion complex using quality by design approach. Methods: A Box-Behnken design was employed to determine effects of variables on selected responses. Risk assessment was conducted using Ishikawa fishbone diagram. A model with a p-value was less than 0.5 for being a significant error of model was determined based on significance 'lack of fit' value. Spheroids were formulated using the extrusion spheronization technique and were characterized using analytical techniques. Results: In vitro release was performed in both acidic (pH 1.2) and simulated intestinal (pH 6.8) conditions. Permeability studies demonstrated tenfold enhancement compared with arteether. In vivo studies further validated increase of 51.8% oral bioavailability. Ex vivo studies revealed 3.4-fold enhancement in antimalarial activity compared with arteether. Conclusion: These findings highlight effectiveness of inclusion complexation technique as a viable approach to enhance solubility and bioavailability for drugs with low aqueous solubility.

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Dynamic Phase Behavior of Surface-Active Fluorinated Ionic Liquid Epoxidation Catalysts.

We report on the synthesis of amphiphobic fluorinated surface-active ionic liquid (FSAIL) epoxidation catalysts, which show reversible temperature-controlled solubility in water. The solubility of FSAILs containing the catalytically active perrhenate- and tungstate anions was studied in both the aqueous and the substrate phase, showing a significant solubility decrease in both media compared to their non-fluorinated congeners. It was shown that both the epoxide product and the catalyst additive phenylphosphonic acid (PPA) are efficient in transferring the FSAIL catalyst into the organic phase, rendering the reaction homogeneous. The FSAILs were used as catalysts for the epoxidation of olefins using aqueous H2O2 as oxidant, showing an exceptionally high catalytic activity at mild conditions. Catalyst recycling was demonstrated over ten consecutive runs by phase separation and subsequent product distillation.

A new ciprofibrate calcium salt with improved solubility and intrinsic dissolution rate.

Ciprofibrate (CIP) is an active pharmaceutical ingredient (API) classified as class II on the basis of biopharmaceutical classification system (BCS), what indicates that it has low solubility in aqueous solvents. The use of API salts has attracted attention due to their improvements in solubility, tolerability, higher rate and extent of absorption, and faster onset of the therapeutic effect. In this work, a new crystalline CIP monohydrated calcium salt (Ca(CIP)2.H2O) was successfully obtained and its crystal structure determined by single crystal X-ray diffraction analysis (SCXRD). Additionally, Ca(CIP)2.H2O was widely characterized by powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and submitted to solubility, intrinsic dissolution and accelerated stability studies. Ca(CIP)2.H2O exhibited higher solubility and dissolution rate than CIP-free form and was stable up to 6 months at 40°C (75%RH). Therefore, Ca(CIP)2.H2O may be a viable alternative for use in solid dosage forms.

Co-amorphous systems of sulfasalazine with matrine-type alkaloids: Enhanced solubility behaviors and synergistic therapeutic potential.

Sulfasalazine (SULF), a sulfonamide antibiotic, has been utilized in the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) since its discovery. However, its poor water solubility causes the high daily doses (1---3 g) for patients, which may lead to the intolerable toxic and side effects for their lifelong treatment for RA and IBD. In this work, two water-soluble natural anti-inflammatory alkaloids, matrine (MAR) and sophoridine (SPD), were employed to construct the co-amorphous systems of SULF for addressing its solubility issue. These newly obtained co-amorphous forms of SULF were comprehensively characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). We also investigated their dissolution behavior, including powder dissolution, in vitro release, and intrinsic dissolution rate. Both co-amorphous systems exhibited superior dissolution performance compared to crystalline SULF. The underlying mechanism responsible for the enhanced dissolution behaviors in co-amorphous systems were also elucidated. These mechanisms include the inhibition of nucleation, complexation, increased hydrophilicity, and robust intermolecular interactions in aqueous solutions. Importantly, these co-amorphous systems demonstrated satisfactory physical stability under various storage conditions. Network pharmacological analysis was utilized to investigate the potential therapeutic targets of both co-amorphous systems against RA, revealing similar yet distinct multi-target synergistic therapeutic mechanisms in the treatment of this condition. Our study suggests these drug-drug co-amorphous systems hold promise for optimizing SULF dosage in the future and providing a potential drug combination strategy.

Edaravone for the Treatment of Motor Neurone Disease: A Critical Review of Approved and Alternative Formulations against a Proposed Quality Target Product Profile.

Edaravone is one of two main drugs for treating motor neurone disease (MND). This review proposes a specific quality target product profile (QTPP) for edaravone following an appraisal of the issues accounting for the poor clinical uptake of the approved IV and oral liquid edaravone formulations. This is followed by a review of the alternative oral formulations of edaravone described in the published patent and journal literature against the QTPP. A total of 14 texts published by six research groups on 18 novel oral formulations of edaravone for the treatment of MND have been reviewed. The alternative oral formulations included liquid and solid formulations developed with cyclodextrins, lipids, surfactants, co-surfactants, alkalising agents, tablet excipients, and co-solvents. Most were intended to deliver edaravone for drug absorption in the lower gastrointestinal tract (GIT); however, there were also four formulations targeting the oral mucosal absorption of edaravone to avoid first-pass metabolism. All the novel formulations improved the aqueous solubility, stability, and oral bioavailability (BA) of edaravone compared to an aqueous suspension of edaravone. A common limitation of the published formulations is the lack of MND-patient-centred data. Except for TW001, no other formulations have been trialled in MND patients. To meet the QTPP of an oral edaravone formulation for MND patients, it is recommended that a tablet of appropriate size and with acceptable taste and stability be designed for the effective sublingual or buccal absorption of edaravone. This tablet should be designed with input from the MND community.

Amorphous Polymer-Phospholipid Solid Dispersions for the Co-Delivery of Curcumin and Piperine Prepared via Hot-Melt Extrusion.

Curcumin and piperine are plant compounds known for their health-promoting properties, but their use in the prevention or treatment of various diseases is limited by their poor solubility. To overcome this drawback, the curcumin-piperine amorphous polymer-phospholipid dispersions were prepared by hot melt extrusion technology. X-ray powder diffraction indicated the formation of amorphous systems. Differential scanning calorimetry confirmed amorphization and provided information on the good miscibility of the active compound-polymer-phospholipid dispersions. Owing to Fourier-transform infrared spectroscopy, the intermolecular interactions in systems were investigated. In the biopharmaceutical properties assessment, the improvement in solubility as well as the maintenance of the supersaturation state were confirmed. Moreover, PAMPA models simulating the gastrointestinal tract and blood-brain barrier showed enhanced permeability of active compounds presented in dispersions compared to the crystalline form of individual compounds. The presented paper suggests that polymer-phospholipid dispersions advantageously impact the bioaccessibility of poorly soluble active compounds.

Optimization of Sodium Iodide-Based Root Filling Material for Clinical Applications: Enhancing Physicochemical Properties.

Premature loss of root canal-treated primary teeth has long been a concern in dentistry. To address this, researchers developed a sodium iodide-based root canal-filling material as an alternative to traditional iodoform-based materials. The goal of this study was to improve the physicochemical properties of the sodium iodide-based material to meet clinical use standards. To resolve high solubility issues in the initial formulation, researchers adjusted component ratios and added new ingredients, resulting in a new paste called L5. This study compared L5 with L0 (identical composition minus lanolin) and Vitapex as controls, conducting physicochemical and antibacterial tests. Results showed that L5 met all ISO 6876 standards, demonstrated easier injection and irrigation properties than Vitapex, and exhibited comparable antibacterial efficacy to Vitapex, which is currently used clinically. The researchers conclude that if biological stability is further verified, L5 could potentially be presented as a new option for root canal-filling materials in primary teeth.

Physical, antibacterial, blood coagulation, and healing promotion evaluations of chitosan derivative-based composite films.

Chitosan is a potentially suitable material for wound dressing, but is undesirably water-insoluble. Although chitosan can be modified to produce water-soluble derivatives, the best chitosan derivative for wound dressings remains unclear. The present study introduced three water-soluble chitosan derivatives, namely, carboxymethyl chitosan, quaternized chitosan (QCS), and carboxymethyl quaternized chitosan, and explored the physical properties, biochemical properties, and wound care effectiveness of films of these derivatives. The QCS-based film exhibited higher absorption ability, mechanical properties, water-vapor permeability, electroconductivity, and antioxidant capacity than the other films. Most importantly, the cationic quaternary ammonium groups facilitated the antibacterial activity (>95 %) and blood coagulant capacity of the QCS-based film. As this film also promoted wound healing, it presented as an ideal candidate for wound dressings.

Mechanochemical synthesis of novel metronidazole cocrystal: Structure characterization and pharmaceutical properties study.

A new cocrystalline form of metronidazole (MET) with propyl gallate (PRO), referred to as MET-PRO, has been successfully synthesized and characterized. Structural characterization reveals that MET and PRO are present in a 1:1 ratio within the cocrystal lattice, with one water molecule equivalent incorporated into the structure. This arrangement facilitates the formation of MET-PRO heterodimers and multiple stable units, collectively constructing a three-dimensional supramolecular network. The solubility and permeability of the current cocrystal, along with the parent drug MET, are evaluated under physiological pH conditions. Experimental findings reveal that MET within the cocrystal exhibits a 1.54-2.37 folds increase in solubility and approximately a threefold improvement in permeability compared to its standalone form. Intriguingly, these concurrent enhancements in the physicochemical properties of MET lead to augmented antibacterial activity in vitro, evidenced by a reduction in minimum inhibitory concentration. Even more intriguingly, the enhanced physicochemical properties observed in vitro for the current cocrystal translate into tangible pharmacokinetic benefits in vivo, characterized by prolonged half-life and enhanced bioavailability. Consequently, this research not only introduces a fresh crystal structure for antibacterial medication but also presents approach for optimizing drug properties across in vitro and in vivo settings, while concurrently bolstering the antibacterial effectiveness of MET through pharmaceutical cocrystallization techniques.

Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses.

BACKGROUND: Solubility is a common feature of allergens. However, the causative relationship between this protein-intrinsic feature and sensitization capacity of allergens is not fully understood. This study aimed to proof the concept of solubility as a protein intrinsic feature of allergens. METHODS: The soluble birch pollen allergen Bet v 1 was covalently coupled to 1 µm silica particles. IgE-binding and -cross-linking capacity was assessed by inhibition ELISA and mediator release assay, respectively. Alterations in adjuvanticity by particle-loading were investigated by activation of dendritic cells, mast cells and the Toll-like receptor 4 pathway as well as by Th2 polarization in an IL-4 reporter mouse model. In BALB/c mice, particle-loaded and soluble Bet v 1 were compared in a model of allergic sensitization. Antigen uptake and presentation was analysed by restimulating human Bet v 1-specific T cell lines. RESULTS: Covalent coupling of Bet v 1 to silica particles resulted in an insoluble antigen with retained IgE-binding and -cross-linking capacity and no increase in adjuvanticity. In vivo, particle-loaded Bet v 1 induced significantly lower Bet v 1-specific (s)IgE, whereas sIgG1 and sIgG2a levels remained unaffected. The ratio of Th2 to Th1 cells was significantly lower in mice sensitized with particle-loaded Bet v 1. Particle-loading of Bet v 1 resulted in a 24-fold higher T cell activation capacity in Bet v 1-specific T cell lines, indicating more efficient uptake and presentation than of soluble Bet v 1. CONCLUSIONS: Our results show that solubility is a decisive factor contributing to the sensitization capacity of allergens. The reduction in sensitization capacity of insoluble, particle-loaded antigens results from enhanced antigen uptake and presentation compared to soluble allergens.

Correlating physico-chemical properties of analytes with Hansen solubility parameters of solvents using machine learning algorithm for predicting suitable extraction solvent.

Artificial neural networks (ANNs) are biologically inspired algorithms designed to simulate the way in which the human brain processes information. In sample preparation for bioanalysis, liquid-liquid extraction (LLE) represents an important step with the extraction solvent selection is the key laborious step. In the current work, a robust and reliable ANNs model for LLE solvent prediction was generated which could predict the suitable solvent for analyte extraction. The developed ANNs model takes a set of chosen descriptors for the cited analyte as an input and predicts the corresponding Hansen solubility parameters of the suitable extraction solvent as a model output. Then, from the solvent combination's appendix, the analyst can identify the proposed extraction solvents' combination for the cited analyte easily and efficiently. For the experimental validation of the model prediction capabilities, twenty structurally diverse drugs belonging to different pharmacological classes were extracted from human plasma. The extraction process was performed using the predicted extraction solvent combination for each drug and quantitively estimated by HPLC/UV methods to assess their extraction recovery. The developed LLE solvent prediction model is in- line with the global trend towards green chemistry since it limits the consumption of organic solvents.

Improvement of solubility, dissolution, and bioavailability of phenytoin intercalated in Mg-Al layered double hydroxide.

Layered double hydroxides (LDHs) are highly effective drug delivery systems, owing to their capacity to intercalate or adsorb biomaterials, flexible structure, swelling property, high stability, good biocompatibility, and ease of synthesis. Phenytoin (PHT) is an antiseizure BCS (Biopharmaceutics Classification System) class II drug, presenting low aqueous solubility. Therefore, the current study aimed at increasing its solubility, dissolution, and bioavailability. PHT was intercalated to the MgAl-LDH formed in situ and successful intercalation to form MgAl-PHT-LDH was confirmed by FTIR, PXRD, DSC, and TGA. Examination of particle size and morphology (by photon correlation spectroscopy and electron microscopy, respectively) confirmed the formation and intercalation of nanostructured LDH. Intercalation enhanced the saturation solubility of PHT at 25°C in 0.1N HCl and phosphate buffer (pH 6.8) by 6.57 and 10.5 times respectively. The selected drug excipient powder blend for the formulation of MgAl-PHT-LDH tablets exhibited satisfactory properties in both pre-compression parameters (angle of repose, bulk density, tapped density, Carr's index, and Hausner ratio) and tablet characteristics (weight variation, thickness, hardness, friability, content uniformity, and disintegration time). MgAl-PHT-LDH tablets showed better dissolution of PHT compared to unprocessed PHT tablets at all time points. Oral bioavailability of MgAl-PHT-LDH tablets and unprocessed PHT tablets was tested in two groups of Sprague Dawley rats based on analysis of serum levels of both forms of PHT by UPLC-ESI-MS/MS serum. MgAl-PHT-LDH tablets demonstrated a relative bioavailability of 130.15% compared to unprocessed PHT tablets, confirming a significantly higher oral bioavailability of MgAl-PHT-LDH. In conclusion, MgAl-PHT-LDH could provide a strategy for enhancing solubility, dissolution, and thereby bioavailability of PHT, enabling the evaluation of theclinical efficacy of MgAl-PHT-LDH tablets for the treatment of seizures at lower PHT doses.

Technical-functional and surface properties of white common bean proteins (Phaseolus vulgaris L.): Effect of pH, protein concentration, and guar gum presence.

Legumes are abundant sources of proteins, and white common bean proteins play an important role in air-water interface properties. This study aims to investigate the technical-functional properties of white common bean protein isolate (BPI) as a function of pH, protein concentration, and guar gum (GG) presence. BPI physicochemical properties were analyzed in terms of solubility, zeta potential, and mean particle diameter at pH ranging from 2 to 9, in addition to water-holding capacity (WHC), oil-holding capacity (OHC), and thermogravimetric analysis. Protein dispersions were evaluated in terms of dynamic, interfacial, and foam-forming properties. BPI showed higher solubility (>80 %) at pH 2 and above 7. Zeta potential and mean diameter ranged from 15.43 to -34.08 mV and from 129.55 to 139.90 nm, respectively. BPI exhibited WHC and OHC of 1.37 and 4.97 g/g, respectively. Thermograms indicated decomposition temperature (295.81 °C) and mass loss (64.73 %). Flow curves indicated pseudoplastic behavior, with higher η100 values observed in treatments containing guar gum. The behavior was predominantly viscous (tg δ > 1) at lower frequencies, at all pH levels, shifting to predominantly elastic at higher frequencies. Equilibrium surface tension (γeq) ranged from 43.87 to 41.95 mN.m-1 and did not decrease with increasing protein concentration under all pH conditions. All treatments exhibited ϕ < 15°, indicating predominantly elastic surface films. Foaming properties were influenced by higher protein concentration and guar gum addition, and the potential formation of protein-polysaccharide complexes favored the kinetic stability of the system.

Statistical Design Approach for the Formulation And Optimization of Nanosponges Using Poorly Water-soluble Candidate.

BACKGROUND AND OBJECTIVES: Nanosponges are one of the most innovative ways to use the newest developments in nanodrugs delivery. Nanosponges can catch drugs that dissolve in water or ones that don't. This work uses statistical design to find the best nanosponges for drugs that don't dissolve easily and make them. MATERIAL AND METHODS: It was looked into how to statistically make the most of the effects of independent factors. The ethyl cellulose ratio and stirring rate were chosen based on how they affected the dependent variables, such as particle size and how well they were trapped. FTIR, SEM, zeta potential, entrapment efficiency, and particle size data were used to test the nanosponges that were made. Using carbopol, the best lot of nanosponges was added to the gel. RESULTS: Using ethyl cellulose and polyvinyl alcohol as stabilizers in the emulsion liquid diffusion method, it was possible to make drug-loaded nanosponges. It was possible to make the nanosponges composition work better by using Central Composite Design. It has been seen that making drug-filled nanosponges improves stability. CONCLUSION: The study showcased the enhanced capacity of a formulation with decreased particle size and high entrapment efficiency to disseminate effectively.

Apparent digestibility and calcium and phosphorus in urine after feeding different combinations of calcium and phosphorus sources to adult dogs.

The present study aimed to investigate the effect of the combination of a water-soluble calcium (Ca) source (CaCl2) with a water-soluble phosphorus (P) source (NaH2PO4*2H2O, diet soluble, SOL) in comparison to a water-insoluble P source (CaHPO4*2H2O, diet insoluble, INS) on apparent digestibility and renal excretion of Ca and P in dogs. The Ca intake was 226 mg/kg bodyweight (bw), the Ca/P ratio 1.9/1 in SOL and 2.0/1 in INS. The percentage of Ca from CaCl2 was 60% in SOL and 33% in INS. Eight adult Foxhound-crossbred dogs FBI, (3-5 years, bw 24-32 kg) were available. Standard digestion trials were carried out (10 days adaptation, 5 days total faecal collection). Spontaneously excreted urine was collected pre- and postprandially. In vitro water solubility of P in the mineral premixes was determined. The Ca digestibility was negative in both trials without significant differences between the groups. Apparent P digestibility was increased in group SOL (26% vs. 20% in INS). In both groups, P content in urine was higher pre- compared to postprandial, with higher concentrations in group SOL. The same was true for the P/Crea ratio. The water solubility of P in the mineral premixes used in the trials showed considerable differences: The P in premix INS was insoluble in water after 1 and after 90 min. By contrast, the P in the premix SOL was highly soluble (98%) after 1 minute. After 90 min, however, the P solubility decreased to 43%, suggesting the formation of insoluble CaP salts, presumably from CaCl2 and NaH2PO4*2H2O. In conclusion, in the present study, apparent Ca digestibility in dogs was not affected by the solubility of Ca and P, while P digestibility and renal P excretion increased.

Conformational changes induced by cellulose nanocrystals in collaboration with calcium ion improve solubility of pea protein isolate.

The low solubility of pea protein isolate (PPI) greatly limits its functional properties and its wide application in food field. Thus, this study investigated the effects and mechanisms of cellulose nanocrystals (CNC) (0.1-0.4 %) and CaCl2 (0.4-1.6 mM) on the solubility of PPI. The results showed that the synergistic effect of CNC (0.3 %) and Ca2+ (1.2 mM) increased the solubility of PPI by 242.31 %. CNC and Ca2+ changed the molecular conformation of PPI, enhanced intermolecular forces, and thus induced changes in the molecular morphology of PPI. Meanwhile, the turbidity of PPI decreased, while surface hydrophobicity, the absolute zeta potential value, viscoelasticity, ß-sheet ratio, and thermal properties increased. CNC bound to PPI molecules through van der Waals force and hydrogen bond. Ca2+ could strengthen the crosslinking between CNC and PPI. In summary, it is proposed a valuable combination method to improve the solubility of PPI, and it is believed that this research is of great significance for expanding the application fields of PPI and modifying plant proteins.

Tuning Ferulic Acid Solubility in Choline-Chloride- and Betaine-Based Deep Eutectic Solvents: Experimental Determination and Machine Learning Modeling.

Deep eutectic solvents (DES) represent a promising class of green solvents, offering particular utility in the extraction and development of new formulations of natural compounds such as ferulic acid (FA). The experimental phase of the study undertook a systematic investigation of the solubility of FA in DES, comprising choline chloride or betaine as hydrogen bond acceptors and six different polyols as hydrogen bond donors. The results demonstrated that solvents based on choline chloride were more effective than those based on betaine. The optimal ratio of hydrogen bond acceptors to donors was found to be 1:2 molar. The addition of water to the DES resulted in a notable enhancement in the solubility of FA. Among the polyols tested, triethylene glycol was the most effective. Hence, DES composed of choline chloride and triethylene glycol (TEG) (1:2) with added water in a 0.3 molar ration is suggested as an efficient alternative to traditional organic solvents like DMSO. In the second part of this report, the affinities of FA in saturated solutions were computed for solute-solute and all solute-solvent pairs. It was found that self-association of FA leads to a cyclic structure of the C28 type, common among carboxylic acids, which is the strongest type of FA affinity. On the other hand, among all hetero-molecular bi-complexes, the most stable is the FA-TEG pair, which is an interesting congruency with the high solubility of FA in TEG containing liquids. Finally, this work combined COSMO-RS modeling with machine learning for the development of a model predicting ferulic acid solubility in a wide range of solvents, including not only DES but also classical neat and binary mixtures. A machine learning protocol developed a highly accurate model for predicting FA solubility, significantly outperforming the COSMO-RS approach. Based on the obtained results, it is recommended to use the support vector regressor (SVR) for screening new dissolution media as it is not only accurate but also has sound generalization to new systems.

Solid Dispersions Obtained by Ball Milling as Delivery Platform of Etodolac, a Model Poorly Soluble Drug.

Poor water solubility of drugs is a limiting factor for their bioavailability and pharmacological activity. Many approaches are known to improve drug solubility, and among them, the physical method, solid dispersions (SDs), is applied. SDs are physical mixtures of a drug and a carrier, sometimes with the addition of a surfactant, which can be obtained by milling, cryomilling, spray-drying, or lyophilization processes. In this study, solid dispersions with etodolac (ETD-SDs) were prepared by the milling method using different carriers, such as hypromellose, polyvinylpyrrolidone, copovidone, urea, and mannitol. Solubility studies, dissolution tests, morphological assessment, thermal analysis, and FTIR imaging were applied to evaluate the SD properties. It was shown that the ball-milling process can be applied to obtain SDs with ETD. All designed ETD-SDs were characterized by higher water solubility and a faster dissolution rate compared to unprocessed ETD. SDs with amorphous carriers (HPMC, PVP, and PVP/VA) provided greater ETD solubility than dispersions with crystalline features (urea and mannitol). FTIR spectra confirmed the compatibility of ETD with tested carriers.

Design and Optimization of Molecularly Imprinted Polymer Targeting Epinephrine Molecule: A Theoretical Approach.

Molecularly imprinted polymers (MIPs) are a growing highlight in polymer chemistry. They are chemically and thermally stable, may be used in a variety of environments, and fulfill a wide range of applications. Computer-aided studies of MIPs often involve the use of computational techniques to design, analyze, and optimize the production of MIPs. Limited information is available on the computational study of interactions between the epinephrine (EPI) MIP and its target molecule. A rational design for EPI-MIP preparation was performed in this study. First, density functional theory (DFT) and molecular dynamic (MD) simulation were used for the screening of functional monomers suitable for the design of MIPs of EPI in the presence of a crosslinker and a solvent environment. Among the tested functional monomers, acrylic acid (AA) was the most appropriate monomer for EPI-MIP formulation. The trends observed for five out of six DFT functionals assessed confirmed AA as the suitable monomer. The theoretical optimal molar ratio was 1:4 EPI:AA in the presence of ethylene glycol dimethacrylate (EGDMA) and acetonitrile. The effect of temperature was analyzed at this ratio of EPI:AA on mean square displacement, X-ray diffraction, density distribution, specific volume, radius of gyration, and equilibrium energies. The stability observed for all these parameters is much better, ranging from 338 to 353 K. This temperature may determine the processing and operating temperature range of EPI-MIP development using AA as a functional monomer. For cost-effectiveness and to reduce time used to prepare MIPs in the laboratory, these results could serve as a useful template for designing and developing EPI-MIPs.