Browsing by Subject "solubility"

Now showing 1 - 4 of 4
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    Discovery, characterization, and pharmaceutical applications of two loratadine- oxalic acid cocrystals
    (2020-08) Liang, Zhengxuan
    Crystallization of multi-component crystals is widely used in pharmaceutical science to enhance the physiochemical properties, such as stability, mechanical properties and solubility. Loratadine (Lor) is a BCS II antihistamine drug commonly used to relieve the symptoms of allergy. It has high permeability but low solubility at physiological pHs. To overcome the problem of low solubility, we synthesized and fully characterized two Loratadine multi-component crystalline phases with oxalic acid (Oxa), i.e., a 1:1 Lor-Oxa conjugate acid-base cocrystal (Lor-Oxa CAB) and a 2:1 Lor-Oxa cocrystal monohydrate (Lor-Oxa hydrate). Both cocrystals exhibited adequate physical stability, enhanced solubility and, higher intrinsic dissolution rate than Lor. The intrinsic dissolution rate of Lor-Oxa CAB is 90 times that of Lor, which makes it a promising candidate for tablet formulation development.
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    Enhancement of Pea Protein Solubility and Thermal Stability for Beverage Applications via Endogenous Maillard-Induced Glycation and Chromatography Purification
    (2022-05) Schneider, Alissa
    Growing demands for non-soy, plant protein sources have guided the rapid expansion of the pea protein ingredient market in recent years. Pea protein has emerged as the most prominent alternative to soy protein, as pea is not a major allergen, non-GM, sustainable, and widely available. Accordingly, a variety of pea protein products are now commercially available, suited for a number of different applications. Pea protein generally exhibits inferior functionality compared to soy protein, however, as a result of its intrinsic protein profile and structure, especially following commercial processing. Namely, pea protein exhibits inferior solubility and thermal stability compared to whey and soy proteins, limiting its application in high-protein, RTD beverages. Enhancement of pea protein solubility under acidic conditions and following thermal treatments is, therefore, of interest.Controlled, Maillard-induced glycation is a protein modification technique that has the potential to improve pea protein solubility and thermal stability. While glycation of pea protein has been reported, this process has not been developed for an industrial scale, unreacted carbohydrates are rarely removed, and all previous studies have utilized exogenous saccharides (e.g., pectin, gum Arabic, and corn maltodextrin), presenting concerns regarding application in “clean label” products. The starch-rich by-product of pea protein extraction may be further processed to produce an endogenous reducing saccharide, such as maltodextrin, which may react with protein under controlled glycation conditions. Glycation coupled with purification of partially-glycated pea protein has the potential to produce a highly soluble and thermally stable protein ingredient with added-value, having potential for RTD beverage applications. Therefore, the main objective of this work was to enhance pea protein solubility and thermal stability by producing an endogenously and partially-glycated pea protein (PG-PP) ingredient by completing several goals: (1) develop a method to produce maltodextrin from pea starch with a specific reducing power, (2) initiate and control the early stage of the Maillard reaction to partially-glycate pea protein isolate (PPI) with pea maltodextrin, (3) remove unreacted maltodextrin from the PG-PP via hydrophobic interaction chromatography (HIC) to produce a purified, PG-PP concentrate or isolate, and (4) characterize the effect of glycation coupled with purification on protein structure and the consequent impact on solubility and thermal stability. A method to produce maltodextrin from the pea starch-rich by-product obtained during the production of native pea protein isolate (nPPI) was developed by monitoring maltodextrin dextrose equivalent (DE) in response to hydrolysis time, small saccharide removal, and centrifugation to remove large molecular weight residual starch and fiber. The resulting chain-length distribution was evaluated. Maillard-induced glycation was then confirmed and monitored by assessing changes in color, free amino groups, and protein/glycoprotein profiles upon incubation of the produced maltodextrin with nPPI. Next, removal of unreacted maltodextrin by HIC was confirmed by monitoring maltodextrin elution. The purified PG-PP, along with purified PPI controls and reference samples (nPPI and commercial PPI), were then characterized by assessing their composition and protein/glycoprotein profile. Protein thermal denaturation properties, surface properties (surface hydrophobicity and zeta potential), and secondary structures were evaluated, as well. Lastly, protein solubility and thermal stability and protein digestibility were assessed. The starch-rich by-product was partially hydrolyzed, with hydrolysis conditions optimized to produce maltodextrin with targeted characteristics (DE 15.7, average degree of polymerization 8.3). PPI and maltodextrin were incubated under mild conditions, which initiated and controlled the Maillard reaction to the early stage. PG-PP was formed with minimal browning and protein polymerization, along with moderate free amino group loss. Additionally, PG-PP was purified by removing the majority of unreacted carbohydrates and polymerized proteins via HIC, resulting in a purified water fraction (PW-PG-PP) with a protein content of nearly 60%, reduced surface hydrophilicity, and increased solubility (up to ~91%) and thermal stability at conditions relevant to RTD beverages. Protein digestibility of PW-PG-PP was high and similar to the references. Purification of nPPI control also produced a highly soluble and thermally stable sample with good protein digestibility. HIC removed hydrophobic and polymerized proteins from nPPI, allowing for the fractionation and concentration of hydrophilic proteins in nPPI. This study proved the concept of “clean-label”, endogenous glycation of pea protein, utilizing endogenously produced maltodextrin and controlled Maillard reaction conditions. Additionally, both endogenous glycation coupled with HIC purification, as well and HIC purification alone, greatly improved the solubility and thermal stability of nPPI under acidic conditions and at a high-protein claim concentration (5% protein), with purified samples having nearly the solubility of whey protein, the gold standard for beverages. These processes also largely maintained the digestibility of PPI. Therefore, glycation and HIC purification created pea protein with potential value for application in high-protein, RTD beverages. Moreover, this work uncovered a PPI fractionation process that has the potential to increase specialty pea protein ingredient value, with the water soluble fraction suitable for beverage applications and hydrophobic fraction suitable for meat analogues. This work also provided foundational information, paving the way for future investigation and process optimization for scaled-up glycation and purification of pea protein.
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    Minnesota Solvation Database (MNSOL) version 2012
    (2020-05-12) Marenich, Aleksandr V; Kelly, Casey P; Thompson, Jason D; Hawkins, Gregory D; Chambers, Candee C; Giesen, David J; Winget, Paul; Cramer, Christopher J; Truhlar, Donald G; truhlar@umn.edu; Truhlar, Donald G; Truhlar Research Group
    The Minnesota Solvation Database consists of a collection of 3037 experimental free energies of solvation or transfer free energies for 790 unique solutes in 92 solvents (including water) and gas-phase M06-2X/MG3S optimized molecular geometries in Cartesian coordinates for the corresponding solutes. All of the 790 solutes in this database (541 neutrals and 249 singly-charged ions) contain at most the following elements: H, C, N, O, F, Si, P, S, Cl, Br, and I.
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    Two-Part Reactive Formulations for Intranasal Delivery of Benzodiazepines
    (2019-08) Rautiola, Davin
    A seizure emergency occurs when an individual experiences a seizure that lasts for more than five minutes (status epilepticus) or multiple distinct seizures with incomplete recovery between them (acute repetitive seizures). A patient experiencing a seizure emergency must be treated as quickly as possible to avoid lasting neurological damage and other life-threatening complications. Benzodiazepines are the primary rescue medications used to treat seizure emergencies, the most commonly used being intravenous lorazepam or rectal diazepam. Despite the effectiveness of these drugs, the delivery routes are not ideal for first-line, outpatient treatments. A skilled caregiver must be present to administer drugs intravenously, and the social stigma associated with rectal administration results in low compliance. Intranasal delivery is an attractive alternative because it requires little training, is easily performed by non-medical personnel, carries a low risk of injury to the patient, and can provide a rapid therapeutic effect. However, formulating a benzodiazepine nasal spray is challenging because these drugs have very low aqueous solubilities. One strategy to circumvent solubility issues relies on in situ production of drug from co-administration of soluble reactants. Herein, we describe how a prodrug/enzyme reaction or an acid/base reaction can be used to deliver a benzodiazepine in an aqueous vehicle with a volume and pH appropriate for intranasal administration. When the soluble components of these two-part reactive formulations are mixed at the time of administration, a metastable supersaturated solution of the benzodiazepine is produced. The supersaturated state of the benzodiazepine provides a large chemical activity gradient for rapid absorption across the nasal mucosa and into systemic circulation. In vitro characterization of the reaction kinetics and supersaturation behaviors for diazepam prodrug/enzyme reactions, midazolam prodrug/enzyme reactions, and midazolam acid/base reactions demonstrated that these two-part formulations generate predictable levels of supersaturated drug. An in vivo pharmacokinetic study in rats showed that rapid absorption and high bioavailability of diazepam results from intranasal administration of a diazepam prodrug/enzyme formulation. Furthermore, a dual chamber nasal spray device capable of mixing and atomizing the components of a two-part formulation was designed, prototyped, and tested. These two-part reactive formulations, coupled with the specialized nasal spray device, exemplify a new intranasal drug delivery strategy that may be applicable to a variety of other drugs with poor stability or low solubility.