Ecotrast-GI: food-based contrast for radiographic imaging of the GI tract
A food-based contrast agent with iodine salts encapsulated in a fruit-vegetable matrix addresses the limitations of existing agents, ensuring accurate dysphagia diagnosis by maintaining natural swallowing and improving patient compliance.
Patent Information
- Application Number
- PCT/US2025/019587
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-03-12
- Filing Date
- 2025-03-12
- Publication Date
- 2026-03-19
AI Technical Summary
Current oral contrast agents for videofluoroscopic swallow studies (VFSS) like barium sulfate and iohexol are not water-soluble, alter swallowing physiology, have unpleasant taste and texture, and pose safety concerns, leading to inaccurate dysphagia diagnosis and patient refusal.
A food-based contrast agent formulation with iodine salts encapsulated in a food-grade carrier matrix, using fruits and vegetables, which is water-soluble, palatable, and maintains natural swallowing physiology, comprising ingredients like fruit juice, sweeteners, drying aids, and bitter blockers to mask the bitter taste of iodine.
The formulation provides stable radiographic visualization, enhances patient acceptance, and ensures safety by mimicking daily diet consistency, reducing false negative results and patient discomfort.
Smart Images

Figure US2025019587_19032026_PF_FP_ABST
Abstract
Description
ECOTRAST-GI: FOOD-BASED CONTRAST FOR RADIOGRAPHIC IMAGING OF THEGl TRACTCROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 63 / 564,376 filed on March 12, 2024, the entire teachings and content of which are incorporated herein by reference.GOVERNMENT SUPPORT CLAUSE
[0002] This invention was made with government support under 2331258 awarded by the National Science Foundation. The government has certain rights in the invention.TECHNICAL FIELD
[0003] The present teachings relate to dysphagia, radiographic procedures, contrast agents, food ingredients and food coatings, and gastrointestinal procedures.BACKGROUND
[0004] Approximately 10-15 million Americans undergo a videofluoroscopic swallow study (VFSS) each year to diagnose and / or monitor dysphagia, which affects people of all ages and is predominantly caused by neurological disorders (stroke, Parkinson's disease, dementia, etc.) as well as premature birth and advanced age. Essential to this radiographic (X-ray) test, which is conducted in tandem by a radiologist and speechlanguage pathologist (SLP), is an oral contrast agent that is mixed with food or liquid to visualize swallowing in real-time via computer monitor.
[0005] The two most commonly used oral contrast agents for VFSS are barium sulfate and iohexol. However, both agents were initially designed for other radiographic tests and have since been adapted for dysphagia diagnosis, resulting in numerous limitations. Barium sulfate is not water soluble; therefore, it falls out of solution after mixing with water and does not retain a stable viscosity within and between patients, compromising standardization of VFSS methodology. Furthermore, barium's viscosity is much higher than water, and its aversive chalky taste and texture do not resemble liquids in a typicaldaily human diet. Importantly, recent research has shown that aspirated barium sulfate remains in the lungs for over a month and induces both acute and chronic immunologic responses and fibrotic changes, raising safety concerns.
[0006] lohexol, FDA approved in 2017 as an alternative to barium sulfate for VFSS, appears safer from a pulmonary perspective, as studies suggest it does not cause discernible acute or chronic pulmonary changes when aspirated in small volumes. However, iohexol is only available as a highly viscous, bitter-tasting liquid that has not yet been optimized for dysphagia diagnostics. Moreover, unlike barium, iohexol breaks down at high temperatures necessary for cooking / baking, making it incompatible with incorporation into chewable food products essential for comprehensive VFSS (e.g., bread, cookie, meat).
[0007] Both contrast agents are known to alter swallowing physiology (particularly swallow timing measures), which may mask swallowing impairment during VFSS. Patients often take smaller bite / sip sizes and demonstrate slower / more controlled bolus transit that reduces the risk of aspiration, potentially leading to false negative results. Additionally, patient refusal due to unpleasant sensory properties is common, particularly among vulnerable populations such as children, elderly patients, and those with cognitive impairments.
[0008] There is, therefore, a significant need for novel food-based contrast agents specifically designed for VFSS that overcome the limitations of current options while maintaining optimal radiographic visualization properties, enhancing patient acceptance, preserving natural swallowing physiology during diagnostic evaluation, and ensuring safety in cases of aspiration.BRIEF SUMMARY
[0009] Described herein is a food-based contrast agent formulation that contains a concentration of iodine salts encapsulated in a food-grade carrier matrix. The food-based contrast formulation is a free-flowing powder. In various embodiments, the food grade carrier matrix is derived from at least one fruit, at least one vegetable, or a mix thereof. Exemplary fruits include blueberry, strawberry, elderberry, cantaloupe, apple, guava, papaya, pear, pomegranate, tomato, date, and any combination thereof. Exemplaryvegetables include beets, potato, sweet potato, bell pepper, carrot, cucumber, squash, lettuce, sweet com, and any combination thereof.
[0010] In various forms, the food-based contrast agent formulation comprises iodine salt between 1 % and 50% of the formulation including 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 80, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, and 50%. In various forms, the foodbased contrast agent formulation comprises iodine salt between 5% and 25% of the formulation. In various forms, the food-based contrast agent formulation comprises iodine salt between 10% and 12%, including 10.1 , 10.2, 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 11 , 11.1 , 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8, 11.9 and 12%. The iodine salts in the food based contrast agent can exist in various forms, without limitation, including as sodium iodide, potassium iodide, or a combination of different iodine salts.
[0011] In various forms, the food grade carrier matrix includes a fruit juice and a drying aid. In various forms, the food grade carrier matrix also includes a sweetener. In various forms, the food grade carrier matrix also includes an acid. In various forms, the food grade carrier matrix also includes a bitter blocker. In various forms, the sweetener can be selected from the group consisting of sucrose, xylitol, maltose, aspartame, sucralose, coconut sugar, honey, vanilla, stevia, monk fruit sweetener, raisin, and any combination thereof. In various forms, the fruit juice is a juice derived from a fruit selected from the group consisting of strawberry, blueberry, blackberry, grapefruit, cantaloupe, papaya, date, elderberry, guava, apple, pomegranate, pear and any combination thereof. In various forms, the drying aid is selected from the group consisting of maltodextrin, gum Arabic, whey protein isolate, plant protein isolate, and any combination thereof. In various forms, the bitter blocker is selected from the group consisting of beta-cyclodextrin, adenosine 5’ monophosphate, and any combination thereof. In various forms, the acid is an organic acid. In various forms, the organic acid is selected from the group consisting of citric acid, malic acid, ascorbic acid, and any combination thereof.
[0012] In various forms, the food-based contrast agent described herein has a pH between 4 and 7 including 4.1 , 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1 , 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1 , 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7. The food-based contrast agent can also have a sweetness as measured on the Brix scale between 4° and90°, including 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 80, 19, 20, 21 , 22, 23, 24, 25,26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48,49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, and 90.
[0013] In various forms, the food-based contrast agent also contains an amount of added water during the formation thereof. The amount of water can vary between 1 and 60%, including 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 80, 19, 20, 21 , 22,23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45,46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, and 60%. In various forms, the amount of water comprises between 20% and 60% including 20, 21 , 22, 23, 24, 25, 26,27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49,50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, and 60%.
[0014] Also described herein is a method of preparing a food-based contrast agent. The method includes blending at least one fruit to obtain a food grade carrier matrix, mixing an iodine salt with the food grade carrier matrix and water to produce a liquid feed, and then encapsulating the iodine salts in the food grad carrier matrix by drying the liquid feed to obtain a food-based contrast agent. The drying technique can any known to one of ordinary skill in the art, including spray drying, spray chilling, freeze drying, emulsification, extrusion, inclusion complexation, and advanced hybrid drying technologies. In various forms, the fruit used in the described method can each be independently selected from the group consisting of blueberry, strawberry, elderberry, cantaloupe, apple, guava, papaya, pear, pomegranate, date, and any combination thereof. In various forms, at least 10% of the liquid feed is iodine salt, at least 60% of the liquid feed is food grade carrier matrix, and at least 20% of the liquid feed is added water. In various forms, less than 12% of the liquid feed is the iodine salt, less than 40% of the liquid feed is the food grade carrier matrix, and less than 60% of the liquid feed is added water.
[0015] Also described herein is a liquid feed for generating a food based contrast agent. The liquid feed includes a concentration of iodine salt, a food grade carrier matrix, and a volume of water. In various forms, the viscosity of the liquid feed is between 1 mPa.s and 250,000 mPa.s. In various forms, the viscosity of the liquid feed is between1.0 mPa.s and 2.0 mPa.s including 1.05, 1.1 , 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 1.95, and 2 mPa.s.BRIEF DESCRIPTION OF THE FIGURES
[0016] FIG. 1 exemplarily depicts a broad high-level diagrammatic depiction of the components of the food-based contrast agent formulation in accordance with various embodiments of the present disclosure;
[0017] FIG. 2 exemplarily depicts a broad high-level diagrammatic depiction of the process of creating the food-based contrast agent formulation in accordance with various embodiments of the present disclosure;
[0018] FIG. 3 exemplarily shows the hygroscopicity of pure iodine samples and spray- dried powders over three days at a relative humidity of 75%;
[0019] FIG. 4 shows the results of the iodine content analysis of different iodine samples;
[0020] FIG. 5 shows a viscosity graph of reconstituted spray dried iodine formulation 12% Nal in the form of shear rate (s-1) vs viscosity mPa.s;
[0021] FIG. 6A shows scanning electron microscopy (SEM) images of pure KI at 40x, 40x, and 1000x magnification;
[0022] FIG. 6B shows SEM images of spray dried 10% KI at 500x, 1500x, and 3000x magnification;
[0023] FIG. 6C shows SEM images of pure Nal at 40x, 200x, and 1000x magnification;.
[0024] FIG. 6D shows SEM images of spray dried 12% Nal at 500x, 1500x, and 3000x magnification; and
[0025] FIG. 7 shows comparisons of the radiodensities of various contrast agents including the food-based contrast agent.DETAILED DESCRIPTION
[0026] The following description is merely exemplary in nature and is in no way intended to limit the present teachings, application, or uses. Throughout thisspecification, like reference numerals will be used to refer to like elements. Additionally, the embodiments disclosed below are not intended to be exhaustive or to limit the invention to the precise forms disclosed in the following detailed description. Rather, the embodiments are chosen and described so that others skilled in the art can utilize their teachings. As well, it should be understood that the drawings are intended to illustrate and plainly disclose presently envisioned embodiments to one of skill in the art, but are not intended to be manufacturing level drawings or renditions of final products and may include simplified conceptual views to facilitate understanding or explanation. As well, the relative size and arrangement of the components may differ from that shown and still operate within the spirit of the invention.
[0027] As used herein, the word "exemplary" or "illustrative" means "serving as an example, instance, or illustration." Any implementation described herein as "exemplary" or "illustrative" is not necessarily to be construed as preferred or advantageous over other implementations. All of the implementations described below are exemplary implementations provided to enable persons skilled in the art to practice the disclosure and are not intended to limit the scope of the appended claims.
[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting. As used herein, the singular forms "a”, "an”, and "the" may be intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms "comprises", "comprising", “including”, and “having” are inclusive and therefore specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. The method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. It is also to be understood that additional or alternative steps can be employed.
[0029] When an element, object, device, apparatus, component, region or section,etc., is referred to as being "on”, “engaged to or with”, "connected to or with”, or "coupled to or with" another element, object, device, apparatus, component, region or section, etc., it can be directly on, engaged, connected or coupled to or with the other element, object, device, apparatus, component, region or section, etc., or intervening elements, objects, devices, apparatuses, components, regions or sections, etc., can be present. In contrast, when an element, object, device, apparatus, component, region or section, etc., is referred to as being "directly on”, “directly engaged to”, "directly connected to”, or "directly coupled to" another element, object, device, apparatus, component, region or section, etc., there may be no intervening elements, objects, devices, apparatuses, components, regions or sections, etc., present. Other words used to describe the relationship between elements, objects, devices, apparatuses, components, regions or sections, etc., should be interpreted in a like fashion (e.g., “between” versus “directly between”, “adjacent” versus “directly adjacent”, etc.).
[0030] As used herein the phrase “operably connected to” will be understood to mean two are more elements, objects, devices, apparatuses, components, etc., that are directly or indirectly connected to each other in an operational and / or cooperative manner such that operation or function of at least one of the elements, objects, devices, apparatuses, components, etc., imparts or causes operation or function of at least one other of the elements, objects, devices, apparatuses, components, etc. Such imparting or causing of operation or function can be unilateral or bilateral.
[0031] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. For example, A and / or B includes A alone, or B alone, or both A and B.
[0032] Although the terms first, second, third, etc. can be used herein to describe various elements, objects, devices, apparatuses, components, regions or sections, etc., these elements, objects, devices, apparatuses, components, regions or sections, etc., should not be limited by these terms. These terms may be used only to distinguish one element, object, device, apparatus, component, region or section, etc., from another element, object, device, apparatus, component, region or section, etc., and do not necessarily imply a sequence or order unless clearly indicated by the context.
[0033] Moreover, it will be understood that various directions such as "upper", "lower","bottom", "top", "left", "right", "first", "second" and so forth are made only with respect to explanation in conjunction with the drawings, and that components may be oriented differently, for instance, during transportation and manufacturing as well as operation. Because many varying and different embodiments may be made within the scope of the concept(s) taught herein, and because many modifications may be made in the embodiments described herein, it is to be understood that the details herein are to be interpreted as illustrative and non-limiting.
[0034] Described herein is a water soluble, food-based eco-friendly contrast agent formulation synthesized from different combinations and formulations of iodine salts and sweeteners, juices, drying aids, water, bitterness blockers, and / or acids derived from natural fruits and vegetables. The contrast agent described herein is encapsulated in a food grade carrier matrix using spray drying techniques, other hybrid dry powder preparation techniques, and / or combination of advanced drying methods. The contrast agent formulation described herein can be readily transformed into a stable liquid, cooked into a food product, or otherwise applied to an easily ingestible medium ideal for use in radiographic tests including swallow tests. The following description begins with a brief high-level description of the composition and assembly of the contrast agent formulation described herein and is followed by a deeper description of how each component is selected, mixed, and processed into each respective final contrast agent formulation.
[0035] FIG. 1 shows a high-level diagrammatic depiction of the ingredients used to prepare the contrast agent powder 100. In various exemplary embodiments, the contrast agent powder 100 comprises an iodine salt and a mixture of processed elderberry, papaya, cantaloupe, and guava. Preparation of the contrast agent powder 100 begins with an iodine salt solution 10 which contains the iodine salts 11. The iodine salts 11 provide the core contrast functionality. Iodine salts contain iodine ions, which efficiently absorb X-rays, creating excellent contrast between tissues and structures during radiographic procedures. When introduced into the body, iodine-based contrast media attenuate X-ray beams more effectively than surrounding tissues, allowing for enhanced visualization of anatomical structures and physiological processes. However, iodine salts typically possess a distinctive bitter and metallic taste that patients find highly unpalatable, causing them to alter their natural swallowing patterns during VFSS with compensatorybehaviors like smaller sips or more cautious swallowing, potentially masking true dysphagia symptoms and compromising diagnostic accuracy.
[0036] Thus, to mitigate this effect, the iodine salts 10 are mixed with a food grade carrier matrix 70, which in various exemplary embodiments include various ingredients selected from a sweetener 20, a fruit juice 30, a drying aid 40, a bitter blocker 50, and an acid 60. In various exemplary embodiments, the food grade carrier matrix is derived from food such as at least one fruit and is generally regarded as safe (GRAS). As detailed in the examples provided below, the food grade carrier matrix 70 is carefully constituted and mixed to balance parameters such as the flavor, pH, production yield, moisture content, and viscosity of both the contrast agent powder 100 and any products derived therefrom. The mixture of the iodine salt solution 10 and the food grade carrier matrix 70 results in a liquid feed 80. The liquid feed 80 then undergoes an encapsulation process 230. The encapsulation process 230 protects the iodine salts 11 and preserves the food grade carrier matrix 70 in a way that preserves the odor, taste, and stability of the non-liquid components of the liquid feed 80. The result of the encapsulation process 230 is the contrast agent powder 100, which is a dried powder containing the iodine salts 11 encapsulated in the food grade carrier matrix 70.
[0037] FIG. 2 provides a detailed flowchart showing a process 200 of selecting, mixing, and processing the iodine salts 11 and the food grade carrier matrix 70 to arrive at the contrast agent powder 100. The process 200 begins with selection of the iodine salts 210. The iodine salts 210 are selected on the basis of solubility in water, as the iodine salts must be dissolved in the iodine salt solution 10, which is aqueous. Table 1 below provides physical properties of various common iodine compounds, including their solubility in water.Table 1 : Physical Properties of Iodine Compounds
[0038] Sodium iodide (Nal) and potassium iodide (KI) are colorless and stand out as having relatively high aqueous solubilities and therefore, in various exemplary embodiments, the iodine salts 11 can comprise Nal, KI, both, or any other water-soluble salt known to one of ordinary skill in the art. Additionally, it is relatively easy to spray dry and encapsulate both Nal and KI despite them being hygroscopic in natural state. Encapsulation of Nal and KI thus further improves the hygroscopicity of the contrast agent powder 100.
[0039] The iodine salts 11 are then dissolved in aqueous solution to generate the iodine salt solution 10. As described above, iodine salts are broadly considered to be unpalatable, so the process 200 then proceeds to a liquid feed preparation 220. Liquid feed preparation 220 comprises mixing the iodine salt solution 10 with the food grade carrier matrix 70. As described above, the food grade carrier matrix 70 comprises at least fruit juice 30 and the drying aid 40. In other various forms, the food grade carrier mix further comprises at least one additional ingredient selected from the group consisting of the sweetener 20, the bitter blocker 50, and the acid 60. The food grade carrier matrix 70 is formulated to render the iodine salts 11 insoluble in saliva by encapsulating the iodine salts 11 , thereby blocking bitter flavors by preventing direct contact between the iodine salts 11 and human taste buds, while simultaneously imparting various desirable physical and chemical characteristics. In various exemplary embodiments, the iodine salt solution 10 comprises the iodine salts 11 in a concentration range between 0.4 g / mL and 1 .5 g / mLIn various exemplary embodiments, the iodine salt solution 10 comprises the iodine salts 11 in a concentration of 0.4 g / mL, 0.5 g / mL, 0.6 g / mL, 0.7 g / mL, 0.8 g / mL, 0.9 g / mL, 1 .0 g / mL, 1.1 g / mL, 1.2 g / mL, 1.3 g / mL, 1.4 g / mL, or 1.5 g / mL
[0040] The sweetener 20 is a compound or mixture that provides one or more flavors, including sweet flavors, to directly counteract bitterness, saltiness, astringency, and other unpleasant flavors. The sweetener 20 can also influence the stickiness and viscosity of the contrast agent powder 100. In various exemplary embodiments, the sweetener 20 is naturally derived from fruits. Examples of the sweetener 20 include but are not limited to sucrose, xylitol, maltose, sucralose, coconut sugar, honey, vanilla, stevia, raisin, palm sugar, other plant-based sugars, and any combination thereof. In various exemplary embodiments, the liquid feed 80 can comprise the sweetener 20 in a range of concentrations sufficient to impart the liquid feed 80 with a sweetness between 4° and 90° on the Brix scale. In various exemplary embodiments, the liquid feed can comprise the sweetener 20 such that the sweetness of the liquid feed 80 is 4° Bx, 5° Bx, 6° Bx, 7° Bx, 8° Bx, 9° Bx, 10° Bx, 11 ° Bx, 12° Bx, 13° Bx, 14° Bx, 15° Bx, 16° Bx, 17° Bx, 18° Bx, 19° Bx, 20° Bx, 21 ° Bx, 22° Bx, 23° Bx, 24° Bx, 25° Bx, 26° Bx, 27° Bx, 28° Bx, 29° Bx,30° Bx, 31 ° Bx, 32° Bx, 33° Bx, 34° Bx, 35° Bx, 36° Bx, 37° Bx, 38° Bx, 39° Bx, 40° Bx,41 ° Bx, 42° Bx, 43° Bx, 44° Bx, 45° Bx, 46° Bx, 47° Bx, 48° Bx, 49° Bx, 50° Bx, 51 ° Bx,52° Bx, 53° Bx, 54° Bx, 55° Bx, 56° Bx, 57° Bx, 58° Bx, 59° Bx, 60° Bx, 61 ° Bx, 62° Bx,63° Bx, 64° Bx, 65° Bx, 66° Bx, 67° Bx, 68° Bx, 69° Bx, 70° Bx, 71 ° Bx, 72° Bx, 73° Bx,74° Bx, 75° Bx, 76° Bx, 77° Bx, 78° Bx, 79° Bx, 80° Bx, 81 ° Bx, 82° Bx, 83° Bx, 84° Bx,85° Bx, 86° Bx, 87° Bx, 88° Bx, 89° Bx, or 90° Bx. In various exemplary embodiments, if the addition of other components of the food grade matrix 70 such as the fruit juice 30 is sufficient to reach a desired level of sweetness for the liquid feed 80, the sweetener 20 can be omitted.
[0041] The fruit juice 30 is juice collected from one or more fruits and / or vegetables and is also intended to provide additional flavor and pleasant odor. In various exemplary embodiments, the flavor profile provided by the fruit juice 30 is more complex than that provided by the sweetener 20 and thus contributes significantly to the palatability of the final contrast agent powder 100. The fruit juice 30 can also positively improve the color of the resulting contrast agent powder 100, which further improves palatability. Examples ofthe fruit juice 30 include but are not limited to the juices derived from strawberry, blueberry, blackberry, grapefruit, cantaloupe, papaya, date, elderberry, guava, apple, pomegranate, pear, beets, potato, sweet potato, bell pepper, carrot, cucumber, squash, lettuce, sweet corn, tomato, other fruits, vegetables and berries, and any combinations thereof. It is noted that some of the members of this group are vegetables and not fruits, however, for ease of explanation, they are all referred to as fruits. In various exemplary embodiments, the concentration range of the fruit juice 30 in the liquid feed 80 is between 20% and 60%. In various exemplary embodiments, the concentration range of the fruit juice 30 in the liquid feed 80 is 20%, 21 %, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31 %, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41 %, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51 %, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%.
[0042] The drying aid 40 is a compound or mixture that facilitates the encapsulation process by providing structural support and controlling moisture during drying, while simultaneously forming a protective matrix around the iodine salts 11 and prevents the iodine salts 11 from dissolving into solution. The drying aid 40 thus functions as both a carrier and stabilizing agent in various encapsulation techniques, enhancing powder flowability and maintaining the physical integrity of the final formulation. Examples of the drying aid 40 include but are not limited to maltodextrin, gum Arabic, carrageenan, xanthan, tragacanth, cress seed gum, Persian / or Angum gum, whey protein isolate, plantbased powders, carbohydrate-based matrices, protein-based matrices, carbohydrate and protein-based matrices, protein and fat-based matrices, and any combinations thereof. In various exemplary embodiments, the drying aid 40 is present in the liquid feed 80 at a concentration between 1 % w / w and 50% w / w. In various exemplary embodiments, the w / w concentration of the drying aid 40 in the liquid feed is 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11 %, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21 %, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31 %, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41 %, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%.
[0043] The bitter blocker 50 is a compound or mixture that suppresses or masks the perception of bitter taste by interacting with bitter taste receptors, binding to bitter compounds, or otherwise interfering with bitter taste signal transduction pathways.Examples of the bitter blocker 50 include but are not limited to beta-cyclodextrin (BCD), adenosine 5' monophosphate (AMP), combinations thereof, and any other bitter blocker known to one of ordinary skill in the art. In various exemplary embodiments, the bitter blocker 50 functions at the taste cell level irrespective of particular composition of the iodine salts 11. In various exemplary embodiments, the bitter blocker 50 is in the liquid feed 80 at a concentration between 0.1 % and 4% w / w. In various exemplary embodiments, the bitter blocker 50 is present in the liquid feed 80 at a w / w concentration of 0.1 %, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1 %, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1 %, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1 %, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, or 4.0%.
[0044] The acid 60 is an acid or combination of acids used to impart additional flavor, suppress bitterness, and preserve the components of the contrast agent powder 100. The acid 60 is sourced from fruits and vegetables and can, in various embodiments, serve multiple functions including adjusting pH to optimal levels for flavor enhancement and stability, creating a tangy taste profile that helps mask the metallic notes of iodine salts, extending shelf-life through antimicrobial activity, and modifying the overall organoleptic properties of the formulation. Common examples include citric acid, malic acid, tartaric acid, and ascorbic acid (vitamin C), which additionally provides antioxidant protection against degradation. In various exemplary embodiments, the acid 60 is at a concentration sufficient for the liquid feed 80 to have a pH between 4 and 7, ideally between 4.6 and6.4, In various exemplary embodiments, the pH of the liquid feed 80 is 4.0, 4.1 , 4.2, 4.3,4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1 , 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1 , 6.2, 6.3,6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7.0. In various exemplary embodiments, the acid 60 is at a concentration sufficient for the contrast agent powder 100 to have a pH between 4 and 7, ideally between 4.6 and 6.4. In various exemplary embodiments, the pH of the contrast agent powder 100 is 4.0, 4.1 , 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1 , 5.2, 5.3, 5.4,5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1 , 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7.0. In various exemplary embodiments, if the pH of the liquid feed 80 and / or the contrast agent powder 100 is within a desired range, the acid 60 can be omitted. In various exemplary embodiments, the viscosity of the liquid feed 80 is between 1 mPa.s and 250,000 mPa.s. In various exemplary embodiments, the viscosity of the liquid feed 80 is between 1.0mPa.s and 2.0 mPa.s. In various exemplary embodiments, the viscosity of the liquid feed 80 is 1.0 mPa s, 1.05 mPa s, 1.1 mPa s, 1.15 mPa s, 1.2 mPa s, 1.25 mPa s, 1.3 mPa s, 1.35 mPa s, 1.4 mPa s, 1.45 mPa s, 1.5 mPa s, 1.55 mPa s, 1.6 mPa s, 1.65 mPa s, 1.7 mPa s, 1.75 mPa s, 1.8 mPa s, 1.85 mPa s, 1.9 mPa s, 1.95 mPa s, or 2.0 mPa s.
[0045] The liquid feed preparation step 220 results in a liquid feed 80, and the liquid feed 80 is processed in the encapsulation process 230. In various exemplary embodiments, the encapsulation process 230 is a spray drying process wherein the liquid feed 80 is first pressurized and forced through specialized nozzles or a rotating atomization disc that creates a fine mist of droplets. The atomized droplets are immediately exposed to a controlled flow of heated air in the drying chamber, causing rapid evaporation of water from the droplet surface. As moisture continuously migrates from the interior to the surface of each droplet, the dissolved solids form a continuous matrix around the active ingredients, resulting in microencapsulated particles. The dried particles then fall to the bottom of the chamber and are collected via cyclone separators, yielding a free-flowing powder with uniform particle size distribution and long shelf-life. The encapsulation process 230 results in the contrast agent powder, which is a free- flowing powder that comprises the iodine salts 11 and residual encapsulating agents 75, which are the dried residuals of the encapsulating agents 70 that are left after the encapsulation process.
[0046] In various exemplary embodiments, at least one and preferably all of the sweetener 20, the fruit juice 30, the drying aid 40, the bitter blocker 50, and the acid 60, or some combination thereof, are derived from natural or synthetic fruits and / or vegetables. In various exemplary embodiments, the liquid feed 80 comprises 10% KI, 50% elderberry, 10% papaya, cantaloupe and guava, and 20% added water. In various exemplary embodiments, the liquid feed 80 comprises 12% Nal, 40% elderberry, papaya, cantaloupe and guava, and 60% added water. In each of the foregoing, the amounts of water and fruit and water are adjusted to account for the balance of the liquid feed in addition to the iodine salt(s). Broadly, in various exemplary embodiments, the liquid feed 80 comprises between 5% and 15% iodine salt, between 20% and 70% blended fruits and / or vegetables, and between 10% and 70% added water. In various exemplary embodiments and without being limiting, the liquid feed 80 comprises iodide salt, blendedfruit and / or vegetable, and water in ratios of 5:20:10, 5:20:20, 5:20:30, 5:20:40, 5:20:50, 5:20:60, 5:20:70, 5:30:10, 5:30:20, 5:30:30, 5:30:40, 5:30:50, 5:30:60, 5:30:70, 5:40:10,5:40:20, 5:40:30, 5:40:40, 5:40:50, 5:40:60, 5:40:70, 5:50:10, 5:50:20, 5:50:30, 5:50:40, 5:50:50, 5:50:60, 5:50:70, 5:60:10, 5:60:20, 5:60:30, 5:60:40, 5:60:50, 5:60:60, 5:60:70, 5:70:10, 5:70:20, 5:70:30, 5:70:40, 5:70:50, 5:70:60, 5:70:70, 6:20:10, 6:20:20, 6:20:30, 6:20:40, 6:20:50, 6:20:60, 6:20:70, 6:30:10, 6:30:20, 6:30:30, 6:30:40, 6:30:50, 6:30:60, 6:30:70, 6:40:10, 6:40:20, 6:40:30, 6:40:40, 6:40:50, 6:40:60, 6:40:70, 6:50:10, 6:50:20,6:50:30, 6:50:40, 6:50:50, 6:50:60, 6:50:70, 6:60:10, 6:60:20, 6:60:30, 6:60:40, 6:60:50, 6:60:60, 6:60:70, 6:70:10, 6:70:20, 6:70:30, 6:70:40, 6:70:50, 6:70:60, 6:70:70, 7:20:10, 7:20:20, 7:20:30, 7:20:40, 7:20:50, 7:20:60, 7:20:70, 7:30:10, 7:30:20, 7:30:30, 7:30:40, 7:30:50, 7:30:60, 7:30:70, 7:40:10, 7:40:20, 7:40:30, 7:40:40, 7:40:50, 7:40:60, 7:40:70, 7:50:10, 7:50:20, 7:50:30, 7:50:40, 7:50:50, 7:50:60, 7:50:70, 7:60:10, 7:60:20, 7:60:30, 7:60:40, 7:60:50, 7:60:60, 7:60:70, 7:70:10, 7:70:20, 7:70:30, 7:70:40, 7:70:50, 7:70:60, 7:70:70, 8:20:10, 8:20:20, 8:20:30, 8:20:40, 8:20:50, 8:20:60, 8:20:70, 8:30:10, 8:30:20, 8:30:30, 8:30:40, 8:30:50, 8:30:60, 8:30:70, 8:40:10, 8:40:20, 8:40:30, 8:40:40, 8:40:50,8:40:60, 8:40:70, 8:50:10, 8:50:20, 8:50:30, 8:50:40, 8:50:50, 8:50:60, 8:50:70, 8:60:10,8:60:20, 8:60:30, 8:60:40, 8:60:50, 8:60:60, 8:60:70, 8:70:10, 8:70:20, 8:70:30, 8:70:40,8:70:50, 8:70:60, 8:70:70, 9:20:10, 9:20:20, 9:20:30, 9:20:40, 9:20:50, 9:20:60, 9:20:70,9:30:10, 9:30:20, 9:30:30, 9:30:40, 9:30:50, 9:30:60, 9:30:70, 9:40:10, 9:40:20, 9:40:30,9:40:40, 9:40:50, 9:40:60, 9:40:70, 9:50:10, 9:50:20, 9:50:30, 9:50:40, 9:50:50, 9:50:60,9:50:70, 9:60:10, 9:60:20, 9:60:30, 9:60:40, 9:60:50, 9:60:60, 9:60:70, 9:70:10, 9:70:20,9:70:30, 9:70:40, 9:70:50, 9:70:60, 9:70:70, 10:20:10, 10:20:20, 10:20:30, 10:20:40,10:20:50, 10:20:60, 10:20:70, 10:30:10, 10:30:20, 10:30:30, 10:30:40, 10:30:5010:30:60, 10:30:70, 10:40:10, 10:40:20, 10:40:30, 10:40:40, 10:40:50, 10:40:6010:40:70, 10:50:10, 10:50:20, 10:50:30, 10:50:40, 10:50:50, 10:50:60, 10:50:7010:60:10, 10:60:20, 10:60:30, 10:60:40, 10:60:50, 10:60:60, 10:60:70, 10:70:1010:70:20, 10:70:30, 10:70:40, 10:70:50, 10:70:60, 10:70:70, 11 :20:10, 11 :20:2011 :20:30, 11 :20:40, 11 :20:50, 11 :20:60, 11 :20:70, 11 :30:10, 11 :30:20, 11 :30:3011 :30:40, 11 :30:50, 11 :30:60, 11 :30:70, 11 :40:10, 11 :40:20, 11 :40:30, 11 :40:4011 :40:50, 11 :40:60, 11 :40:70, 11 :50:10, 11 :50:20, 11 :50:30, 11 :50:40, 11 :50:5011 :50:60, 11 :50:70, 11 :60:10, 11 :60:20, 11 :60:30, 11 :60:40, 11 :60:50, 11 :60:6011 :60:70, 11 :70:10, 11 :70:20, 11 :70:30, 11 :70:40, 11 :70:50, 11 :70:60, 11 :70:7012:20:10, 12:20:20, 12:20:30, 12:20:40, 12:20:50, 12:20:60, 12:20:70, 12:30:1012:30:20, 12:30:30, 12:30:40, 12:30:50, 12:30:60, 12:30:70, 12:40:10, 12:40:2012:40:30, 12:40:40, 12:40:50, 12:40:60, 12:40:70, 12:50:10, 12:50:20, 12:50:3012:50:40, 12:50:50, 12:50:60, 12:50:70, 12:60:10, 12:60:20, 12:60:30, 12:60:4012:60:50, 12:60:60, 12:60:70, 12:70:10, 12:70:20, 12:70:30, 12:70:40, 12:70:5012:70:60, 12:70:70, 13:20:10, 13:20:20, 13:20:30, 13:20:40, 13:20:50, 13:20:6013:20:70, 13:30:10, 13:30:20, 13:30:30, 13:30:40, 13:30:50, 13:30:60, 13:30:7013:40:10, 13:40:20, 13:40:30, 13:40:40, 13:40:50, 13:40:60, 13:40:70, 13:50:1013:50:20, 13:50:30, 13:50:40, 13:50:50, 13:50:60, 13:50:70, 13:60:10, 13:60:2013:60:30, 13:60:40, 13:60:50, 13:60:60, 13:60:70, 13:70:10, 13:70:20, 13:70:3013:70:40, 13:70:50, 13:70:60, 13:70:70, 14:20:10, 14:20:20, 14:20:30, 14:20:4014:20:50, 14:20:60, 14:20:70, 14:30:10, 14:30:20, 14:30:30, 14:30:40, 14:30:5014:30:60, 14:30:70, 14:40:10, 14:40:20, 14:40:30, 14:40:40, 14:40:50, 14:40:6014:40:70, 14:50:10, 14:50:20, 14:50:30, 14:50:40, 14:50:50, 14:50:60, 14:50:7014:60:10, 14:60:20, 14:60:30, 14:60:40, 14:60:50, 14:60:60, 14:60:70, 14:70:1014:70:20, 14:70:30, 14:70:40, 14:70:50, 14:70:60, 14:70:70, 15:20:10, 15:20:2015:20:30, 15:20:40, 15:20:50, 15:20:60, 15:20:70, 15:30:10, 15:30:20, 15:30:3015:30:40, 15:30:50, 15:30:60, 15:30:70, 15:40:10, 15:40:20, 15:40:30, 15:40:4015:40:50, 15:40:60, 15:40:70, 15:50:10, 15:50:20, 15:50:30, 15:50:40, 15:50:5015:50:60, 15:50:70, 15:60:10, 15:60:20, 15:60:30, 15:60:40, 15:60:50, 15:60:6015:60:70, 15:70:10, 15:70:20, 15:70:30, 15:70:40, 15:70:50, 15:70:60, or 15:70:70Alternatively, the blended fruits and / or vegetables can also comprise non-fruit and nonvegetable sources of one or more of the encapsulating agents 70.
[0047] The particular composition of the contrast agent powder 100 thus depends directly on the composition of the liquid feed 80. Broadly, in various exemplary embodiments, the contrast agent powder 100 comprises between 5% and 40% iodine salts 11 and between 60% and 95% residual encapsulating agents 75. In various exemplary embodiments and without being limiting, the contrast agent powder 100 comprises the iodine salts and the residual encapsulating agents 75 in ratios of 5:95, 6:94, 7:93, 8:92, 9:91 , 10:90, 11 :89, 12:88, 13:87, 14:86, 15:85, 16:84, 17:83, 18:82,19:81 , 20:80, 21 :79, 22:78, 23:77, 24:76, 25:75, 26:74, 27:73, 28:72, 29:71 , 30:70, 31 :69, 32:68, 33:67, 34:66, 35:65, 36:64, 37:63, 38:62, 39:61 , and 40:60. In various exemplary embodiments, the contrast agent powder 100 comprises the iodine salts 11 in a concentration of 1 % to 50% w / w. In various exemplary embodiments, the contrast agent powder 100 comprises the iodine salts 11 in a concentration of 5% to 15% w / w. In various exemplary embodiments, the contrast agent powder 100 comprises the iodine salts 11 in a concentration of 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10.0%, 10.5%, 11.0%, 11.5%, 12.0%, 12.5%, 13.0%, 13.5%, 14.0%, 14.5%, or 15.0% w / w.SPECIFIC EXAMPLESEXAMPLE 1 : Materials and Methods
[0048] Iodine (I2), (potassium iodide (KI), potassium iodate (KIO3), sodium iodide (Nal), calcium iodide (Cah), magnesium iodide (Mgh), bitter blockers, and organic acids were bought from Thermo Fisher, Columbia, MO. The sweeteners, organic fruits, and other flavoring agents were purchased from local markets except for the elderberry samples were collected from the University of Missouri Horticulture and Agroforestry Research Center (39° 0'55 “N 92°45'5” W, New Franklin, MO, USA).
[0049] Cantaloupe, guava, papaya, elderberry, strawberry, blueberry, apple, pear, and pomegranate fruits were thoroughly washed before blending. Next, the fruits were cut into halves discarding the skins and keeping only the pulp. About 200g of fruit was used with 100 ml of DI water while blending, and additional 50 ml was added gradually to prepare the juice samples. The blended juices were then strained using an ultra-fine cheesecloth. After straining, the fruit juices were centrifuged in 500 ml bottles at 5000 rpm for 20 minutes to obtain the juice without the solid particles. After centrifuging, the pH of all the fruit juices was measured. The juices were stored at 4° C and later brought to room temperature before the experiment.
[0050] Iodine is the naturally occurring, heaviest member of halogens. Free iodine does not occur in nature. Six different forms of iodine, including elemental iodine, are used in the preliminary observational study process, and based on cost-effectiveness, water solubility, hygroscopicity, and spray drying parameters.
[0051] Depending on the cost-effectiveness, all the iodine compounds are cheapexcept for Mgk. In order to minimize the production cost of the final products, Mgh was excluded from the preliminary screening process, but is included as a potential iodine source for the different formulations as cost was the only factor that excluded it from testing.
[0052] The five iodine compounds were then tested for water solubility. Elemental iodine (I2) is soluble in water but in a minimal amount of 330mg / L at 25° C. Moreover, Elemental I2 is unstable in nature and can readily sublime in the environment, and it is bluish-black in color with a sharp acrid taste. Therefore, elemental iodine was also excluded after the preliminary screening studies, but remains as a potential iodine source that could be used. On the other hand, potassium iodide (KI) is highly soluble in water which is 148 g / 100 g of water at 25° C. Also, it is stable in dry air. Thus, KI was selected for further experiments after the preliminary screening process.
[0053] On the other hand, the solubility of KIO3 is very low, which is 9.16g / 100g of water at 25° C, but Nal is very soluble in water. Moreover, KIO3 is not hygroscopic, and Nal is hygroscopic in nature; however, with optimized spray drying parameters, KlOsand Nal can be used in the final formulation. Thus, KI, Nal, and KlOswere utilized for further taste masking experiments after the preliminary screening process.EXAMPLE 2: Spray Drying
[0054] Spray drying was performed using a laboratory spray dryer BUCHI Mini Spray Dryer B-290. The spray drying parameters at various combinations of inlet air temperature (°C), feed rate (%), nozzle size (pm), outlet temperature (°C), and aspirator optimized based on previously optimized spray drying parameters for iodine solution.. In each experiment 100 ml of feed solution was spray-dried. A humidifier connected to the system was used to get finer flowable powder, as some of the iodine compounds are hygroscopic in nature. Before initiating the spray drying experiments, the spray dryer system was run for 10 minutes with DI water to obtain a steady state condition. The spray-dried powders were kept at 4 °C in sealed glass bottles until utilized for further analysis.
[0055] The drying aid maltodextrin and gum arabic both have benefits in the spray drying process, however, maltodextrin's amorphous nature is to become sticky due to moisture absorption when stored in settings with a high relative humidity level (Wang etal., 2013). Also, degradation may occur during the storage period. Additionally, the absence of emulsifying activity is what restricts its use (Carneiro et al., 2013). Thus, maltodextrin and gum Arabic (GA) were excluded from further experiments due to low glass transition temperature and amorphous nature. However, it is noted that they remain useful in some applications and are still options for the drying aid component.EXAMPLE 3: Partial / Fractional Factorial Design and Encapsulation Agent Selection
[0056] To assess the effects of various parameters on production yields, moisture content, particle size, pH, and flowability, factorial experimental designs were run by using the software JMP 14 with three independent variable parameters of the spray dryer (inlet temperature, aspirator, and feed rate). A fractional factorial design was made depending on drying aid, sweeteners, organic acids, bitter blockers, and organic fruit juices. To reduce the number of experiments, fractional factorial screening designs were initially made. Pre-experiments were conducted to establish appropriate ranges for the processing variables. Thus, the inlet temperature range was selected between 120-180 °C, aspirator 80-100%, and feed rate 10-40. These ranges can scale based on the type of spray dryers from lab scale to pilot scale to industrial scale depending on the manufacturer of the system, while keeping the temperature and aspirator and varying the feed rate.
[0057] Considering the benefits, maltodextrin and gum Arabic was used in the spray drying process as a wall material. Exemplary samples tested in spray drying applications are provided below in Table 2.Table 2 Experimental Design Using Drying Aids in the Spray Drying Formulation
[0058] Using sweeteners is the primary approach towards taste masking, which is also a sensory-based approach to abolish bitterness, excessive saltiness, astringency, off-flavor, or metallic taste. Both artificial and natural sweeteners are frequently used in combination with other taste-masking strategies to increase the efficacy of this technique. Sweeteners may increase the sweet taste and palatability of the product for consumers. However, sugar can contribute to the stickiness of the powder (Muzaffar et al., 2015), and drying sticky foods presents a challenge under standard spray drying circumstances. Sticky foods tend to stick to the dryer wall or may turn into undesirable agglomerates in the dryer chamber and in cyclone separator, which causes operational issues and low product output. Moreover, sweeteners like aspartame are unstable in nature when exposed to heating and have a slight after taste characterized as bitter or metallic. Thus, it was decided not to proceed with using sweeteners in the spray drying process due to stickiness in the drying wall. Table 3 shows how both natural and artificial sweeteners were used, such as sucrose and aspartame. Again, this does not exclude their use for the compositions and methods of this disclosure, they were just not used for this testing phase.Table 3: Experimental Design Using Sweeteners in the Spray Drying Formulation
[0059] Citric, malic, and ascorbic acid were used in the spray drying process. Though the addition of organic acids may help suppress bitter taste and increase palatability, and improve the preservation process, a high concentration of organic acid can have an overpowering effect that may surpass the positive impact. Moreover, spray drying with organic acids may lead to a low glass transition temperature, and due to adhesion, it is difficult to dry in the drying chamber in normal condition. In this research, the organic acid lowered the pH of the spray-dried powder solutions, the color was changed to blackish yellow in the presence of the iodine compound, and at the same time, the powder was sticking to the dryer wall and was hard to scrape out. Thus, organic acids were not used in the final formulation. However, this does not exclude them from the scope of thisdisclosure as they are able to work. Examples of samples including acids derived from natural sources are shown in Table 4 below.Table 4: Experimental Design Using Acids in the Spray Drying Formulation
[0060] Bitter blockers such as cyclodextrin are mainly used in taste masking due to their water solubility properties, stability, better drug loading properties, wetting, and absorption quantity. On the other hand, adenosine 5’ Monophosphate or AMP is highly soluble in water 100mg / ml, which is higher than the effective concentration. It is also stable and maintains its initial concentration even after 25 weeks of storage condition. Hence, the experimental design was made considering the two bitter blockers as shown in Table 5 below. Although bitter blockers may have some advantages in masking the taste; however, the disadvantages may impact the final result in the experiment. Betacyclodextrin may decrease taste and smell and increase irritation in the mouth, and it is toxic at high concentrations, thus limiting the dosage level of bitter blockers in the formulation. However, AMP starts degrading at room temperature, and due to its savory taste, it may not be acceptable to consumers. As with many potential components for the final formulation, these undesirable characteristics do not exclude them from the scope of the disclosure herein.Table 5: Experimental Design Using Bitter Blockers in the Spray Drying Formulation
[0061] To maintain a neutral pH, 10 different alkaline fruits were considered, and their pH values were noted. Fruits with a pH above 4 and low in sugar content were selected for further experiments. Elderberry, cantaloupe, papaya, and guava have low sugar compared to other fruits. Although strawberry contains a low amount of sugar, the pH value was low compared to elderberry, cantaloupe, guava, and papaya. Dates have neutral pH but the sugar content was too high, which might affect the spray drying process. Thus, the final formulation concentrations for any specific application or formulation will be chosen in part depending on the spray drying parameters. pH and sugar content of select fruit juices are provided in Table 6 below, and Table 7 below provides experimental designs for fruit juice blends and iodine salts in a spray drying formulation. Organic fruits that are almost neutral in pH with low sugar content were used to prepare the final feed formulation. The concentration of the juice blends was determined depending on the spray drying parameters. Organic fruit juices contribute to a sweet smell and attractive color to the end product, increasing consumer acceptability. However, the only disadvantage of spray drying of fruit juice is that it cannot be spray dried at high humidity and high concentration which might create stickiness onto the dryer wall. Although, this problem was solved by using a humidifier and controlling the concentration of the juices. 12% Nal and 10% KI with fruit juices provide a high yield and good quality flowable powder. In addition, the pH of the final spray-dried powder was near neutral. The use of KIO3 was excluded in the final formulation as it was clogging the nozzle and feed pump of the spray dryer due to low solubility which led to waste of sample and time.Table 6: pH and Sugar Content of 10 Different Organic Fruit JuicesTable 7: Experimental Design Using Organic Fruit Juice Blends in Spray Drying FormulationEXAMPLE 4: Powder Yield
[0062] After spray drying, the weight of the recovered powder from the collection chamber was recorded to calculate the product yield (n=3). Then, powder yield was calculated where the percentage ratio between the overall mass of spray-dried powder recovered and the quantity of initial feed introduced to the system was used (dry-basis).Product yield 100
[0063] The powder yield is a significant indicator of the effectiveness and economics of the production process. The intended output is indicated by a higher product yield (%) when factors like intake temperature, aspirator, and feed rate are considered. Feed rate, aspirator, and inlet temperature are complexly influenced by powder yield. After spray drying, the powder was collected from both the collection chamber and the cyclone separator.
[0064] The sticky nature of the powder affects the powder yield as it may stick to the wall of the drying chamber, making it hard to scrape out. The recovered powder was then weighed to determine the yield percentage and recovery percentage. Powder yield was high for 10%KI formulation compared to the 12% Nal formulation. A primary difficulty with spray drying of Nal is that Nal is hygroscopic in nature, meaning Nal will absorb waterfrom the atmosphere, mainly occurring at room temperature. Due to this nature, Nal tends to stick to the wall of the spray dryer while spray drying, which reduces the yield percentage of the powder.
[0065] The powders' moisture content and water activity were collected as soon as obtaining the powder from spray drying. The flow properties of the powder are heavily influenced by moisture content, which also impacts the stickiness, caking, and clumping of powder. The moisture content of the spray-dried 10% KI was found 1 ,08±0.03 %, while it was 0.29±0.01 % for the 12% Nal formulation. The low moisture content indicates powder stability, lower risk of oxidative decomposition and microbial activity. Low moisture content also decreases agglomeration and enhances the powder's solubility following reconstitution in water.
[0066] The water activity of the spray-dried 10% KI and 12% Nal formulation was obtained, and it was 0.18±0.01 and 0.11 ±0.00, respectively. Water activity has been the foundation of numerous food preservation techniques throughout history, either by itself or in conjunction with other environmental factors. It is an essential factor for measuring the growth of microbial activity where higher water activity indicates the easy growth of microorganisms and 0.97 water activity is optimal for the growth of microorganisms like Clostridium botulinum, Escherichia coli, Bacillus subtilis, and Listeria monocytogenes. No microbial growth occurs when the water activity is 0.6 or lower. Thus, considering the results, it can be said that the moisture content and water activity values for the spray- dried powders were within the range of commercial norms for food powders. The pH of the spray-dried 10% KI and 12% Nal was calculated 4.43±0.00 and 5.37±0.00, respectively. Compared to the pH of pure KI and Nal samples, the pH of the spray-dried powders was lower. This may be due to the availability of an organic juice blend in the powder formulation. Table 8 below shows spray drying parameters that were used.Table 8: Spray-Drying Parameters With Powder Yield%, Moisture Content, Water Activity and pH Values of Spray-Dried SamplesEXAMPLE 5: Color Value
[0067] The color value of the final spray-dried powder recovered was calculated by L* a*, and b* indexes using a portable chromameter (Konica Minolta CR-410, Chiyoda, Tokyo, Japan). The L* (brightness / darkness), a* (redness / greenness), and b* (yellowness / blueness) values were noted. The measurement was done using 47mm petri dishes as it is the right size to suit the colorimeter opening. The colorimeter was calibrated before each use as instructed by the manufacturer. Three measurements were made for each sample, and the average result was reported. The chroma value and hue angle were determined using the following equations:Chroma (CHue Angle
[0068] The color of any product represents crucial quality parameters that influence how well consumers of all groups would accept the product. Changes in temperature, moisture content, and processing conditions all have an impact on the color value of food products. Moreover, Millard reaction could happen during spray drying at high temperatures and change the desirable color of the product. A significant change in color during processing might cause the consumer to reject the product. For each powder sample, the Commission Internationale d'Eclairage (CIE) L, a, and b values were determined; L is a measure of how white the sample is, +a denotes red color, a denotes green color, b denotes blue color, and +b denotes yellow color. Table 9 shows that thepure samples have high L value compared to the spray-dried samples. The L value for 10% KI spray dried powder and 12% Nal spray dried powder is 58.51 ±0.07 and 71.00±0.03 respectively, whereas the L value for pure sample for both KI and Nal is 80.54±0.25 and 81.78±0.11 respectively. This difference in L value is due to the elderberry, guava, papaya, and cantaloupe juice in the spray-dried powder. Moreover, 12% Nal has a higher L value due to the different concentrations of juice added to the feed solution, which is less compared to 10% KI.
[0069] The highest a value was observed for 10% KI spray-dried powder, and the highest b values were obtained for 12% Nal sample. The hue angle was calculated based on these observations. Hue describes how color is seen in its most basic form as represented by the dominant wavelength. It can be described as the degree of redness and yellowness, with 0 or 360 denoting red, 90 denoting yellow, 180 denoting green, and 270 representing blue. The hue angle value ranges from -14.68 to 74.78, and a negative hue angle was found for pure Nal and 10% KI. Saturation and color intensity is represented by chroma, whereas the hue angle value describes how a color is perceived. The chroma values ranged from 0.49 to 19.31 , indicating the low color intensity of the pure KI, and as they are white color in nature, whereas 10% KI and 12 % Nal samples had higher chroma values as juice was added to the formulation.Table 9: Color Value Analysis of the Pure Iodine Samples and Spray-Dried PowderEXAMPLE 6: Water Activity
[0070] The water activity (aw) of spray-dried powder was analyzed using a water activity meter (Cx-2, Decagon Devices, Inc., Pullman, Washington) at 25 °C with a 0.001 sensitivity. The spray-dried powder was spread evenly on the plastic disc and recorded in triplicates, taking approximately 5-10 minutes to record one data point.EXAMPLE 7: Moisture Content, Hygroscopicity, and Density Measurement
[0071] About 1 g of spray-dried powder in a tared sample pan had its moisture content measured using a halogen moisture analyzer (HE53, Mettler Toledo, Columbus, Ohio 43240). The process was carried out three times for each powder sample.
[0072] The (Sarabandi et al., 2018) method was used to measure the hygroscopicity of spray-dried powder with a little modification. A portion of the material, around 0.5 g, was dried for three days at 25 °C with saturated NaCI solution (75% relative humidity). In order to determine hygroscopicity, the mass of water absorbed per 100 g of dry sample was measured over the course of three consecutive days at the same time.
[0073] Hygroscopicity plays a crucial role in the constitutive behavior of bulk solids and has been recently addressed by. The amount of water stored in powders and bulk solids is influenced by relative humidity, which significantly impacts the effectiveness of bulkhandling machinery used in the packaging sector. FIG. 3 shows the progression of the powder’s hygroscopicity at 75% humidity over three days. Samples with lower hygroscopicity are less sticky and simpler to handle and package. The water absorption rate of the pure iodine and spray-dried samples increased on both the second and third day. The hygroscopicity values ranged from 4.51 ±0.00 to 4.81 ±0.27 where the lowest value was for pure KI samples and the highest value was for pure Nal samples.
[0074] The bulk density ( b) of the spray-dried powder was examined. First, the volume of 2 g spray dried powder was measured into a plastic graduated cylinder with a 10 ml capacity. The bulk density was then estimated by dividing the weight of the powder by its volume. For measuring tap density (pt), 2 g powder sample was added into a 10 ml plastic graduated cylinder and was tapped using a mechanical shaker (IKA-VIBRAX-VXR, Janke & Kunkel, Markham, ON, Canada) at 1000 rpm for 20 minutes. All the experiments were replicated three times, and the average value of the powder was recorded. A gaspycnometer (Quanta chrome Ultra pycnometer 1000 Anton Paar, Graz, Austria) was used to estimate the spray-dried powder's true density. The sample chamber was filled with 4 g of powder, and a preset volume of pressurized helium was allowed to enter the sample cell containing the powder. The true powder density was calculated as the weight of the powder in the sample cell divided by the volume determined by the pycnometer. The average figure was shown, and the equipment was set to run three times in multi-run mode. This procedure was applied three times with a different powder sample. The pycnometer was calibrated before use in accordance with the manufacturer's instructions.EXAMPLE 8: Flowability
[0075] The flow behavior of powder samples was analyzed by calculating the Carr Index (Carr Jr, 1965) and Hausner ratio (Hausner, 1967) from tapped density and bulk density. The equations below were used to calculate the Carr index and Hausner ratio, respectively. Powders with HR less than 1.1 and Cl less than 10 are considered as very free-flowing powders.Carr IndexHausner Ratio (HR) = —
[0076] With some modification, the angle of repose of powders was analyzed using the method described by (Beakawi Al-Hashemi & Baghabra Al-Amoudi, 2018) with some changes. First, a stand was used to suspend a funnel 10 cm above a horizontal surface. The height and width of the heap created by pouring one gram of powder through the funnel were then calculated using the following equation where H= height of the heap and D = diameter of the base.Angle of repose (°) = tan-1(^)
[0077] The angle of repose values for spray-dried samples and pure iodine samples are shown in Table 10, and it was interpreted according to the powder flowability classification by (Carr Jr, 1965) (Hausner, 1967). The angle of repose is the angle formed between the slope of the pile and a horizontal plane when the pile is stationary. The angle of repose explains the flowability characteristics of the sample; a sticky powder particle would have a high angle of repose and reduced flowability. Food industries specificallyrequire a low angle of repose as it is related to the processing and storage condition of the powder samples.
[0078] The angle of repose values less than 30° indicates the very free-flowing nature of the powders. Table 10 shows that there is a significant difference (p<0.05) in the angle of repose values among the pure iodine samples and spray-dried samples, with values ranging from 18.50 for 12% Nal to 24.35 pure Nal sample. Low angle of repose materials flows smoothly, which means the powder particles are not cohesive and a low heap requires relatively little energy to move.Table 10: Physical and Functional Characteristics of the Pure Iodine Samples and Spray-Dried PowdersNote: Each value is the mean of measurements taken 3 times ± SD. Different letters indicate significantly different values (p<0.05) in the same column.
[0079] The density of the particles influences how easily the powder may be handled and transported. These three different types of density are tap, aerated, and poured density. In aerated bulk density, the sample is aerated for maximum volume, in poured density, the sample is poured into a graduated cylinder, and for tap density sample istapped for getting the result. These powders' functional characteristics are influenced by a variety of inherent and external factors.
[0080] The bulk, tap, and true density of all the samples were calculated in Table 10. The bulk density of pure samples and spray-dried powder samples was found to be significantly different (p <0.05). The bulk density of spray-dried powders was lower than pure iodine samples. The lowest was found for 10% spray-dried sample, which was 0.40±0.00, and the highest was found for pure Nal, which was 2.07±0.13. Bulk density is influenced by sample particle size, distribution, friction, and cohesive forces of the particles, and these factors control to which degree the particles will collapse and fill the interspatial spaces depending on these variables.
[0081] Tap density was also found to be higher for pure iodine samples compared to spray-dried samples. The highest tap density was 2.28±0.20 and the lowest was for 12% nal, which was 0.50±0.02. The tap density of the pure sample and spray-dried powder sample was also found to be significantly different (p<0.05). The porosity values of the powder were calculated based on bulk and true density. The mean porosity values ranged from 39.83±0.28 % for pure Nal to 82.17±0.47 % for the 12 % Nal sample. Carr Index, Hausner ratio, and angle of repose were determined to understand the flow properties and compressibility of powder samples. The results are shown in Table 11 .Table 11 : The Flow Behavior of the Pure Iodine Sample and Spray Dried Powder Sample
[0082] Powders with a Carr index greater than 25% are regarded as non-free-flowing, while those with a Hausner ratio greater than 1 .34 are thought to be cohesive and less free-flowing. There was a significant difference (p<0.05) in the Cl and HR ratio values for all the powders. The HR ratio ranges between 1.04 to 1.25, where a pure KI sample is excellent, or very free flowing and 10% spray-dried KI is fair. In this study, all the pure iodine samples and spray-dried samples exhibited good flow properties. However, spray- dried powders were less flowing compared to the pure samples.EXAMPLE 9: pH
[0083] The pH of a liquid reconstituted powder sample was measured using a digital pH meter (Metier Toledo TM) with a pH electrode (In Lab® Expert Pro-ISM), following calibration using a standardized buffer solution at pH 7.00. The sample consisted of 2.5g of spray dried powder added to 5 ml of DI water and mixed thoroughly. The sample pH value was taken in triplicate, and average data was calculated.EXAMPLE 10: Iodine Content Analysis Using ICP-MS
[0084] The pure iodine samples and spray-dried samples were analyzed to determine potassium (K), sodium (Na), and iodine (I2) using inductively coupled plasma mass spectrometry or (ICP-MS), which is commonly used for elemental detection. This method effectively detects many components coming from a single solution in a single measurement. All the powders were weighed into pre-cleaned, pre-weighed polypropylene tubes. Spray-dried 10% KI and 12% Nal powder aliquots were approximately 100-120 mg, whereas Pure KI and Nal powder sample aliquots were 125- 175 mg. Ultrapure water (approx. 10 mL) was added to the powders, and the solution was mixed to dissolve all solids. The tubes were re-weighed to calculate the exact mass of the solution. The intense color of the two spray-dried powder solutions faded quickly in less than a minute.
[0085] Solutions were quickly diluted by a factor of approximately 100X in a diluent of 0.64M NH4OH in ultrapure water. All dilutions were done gravimetrically in order to calculate exact dilution factors. From these intermediate dilutions, further dilutions wereprepared for ICP-MS analysis. Internal standards (Li, Mo, and Cs) were added to all solutions to be run on the ICP-MS. The two spray-dried powder solutions were run at ~1 ,000X and ~10,000X to get all analytes into the best quantifiable range. However, results were consistent between the two dilution sets. Calibration standards were prepared from single-element High Purity Standards stock solutions. Two calibration series were used - a mixed Na / K solution and a solution of iodide (NH4I source). All calibration standards and blanks were prepared with the 0.64M NH4OH diluent, with Li / Mo / Cs internal standards added. Solutions were analyzed on a PerkinElmer NexION 300X instrument operated in KED (Kinetic Energy Discrimination) mode with a He flow of 3.5 mL / min. A glass nebulizer and spray chamber, with a quartz injector tube and torch, were used as the sample introduction system, lohexol was used as a control sample. The liquid 10 ml iohexol sample was diluted in 0.64M NH4OH - two different dilutions (total dilution factors of approximately 22,000 and 44,000) were prepared for analysis. The final dilutions had Li / Mo / Cs internal standards added.
[0086] The ICP-MS analysis of the pure iodine samples and spray dried samples shows the amount of iodine retained before and after the spray drying. ICP-MS was done for only the 10% spray dried Nal sample to find the amount of iodine content and determine if the iodine needs to be increased in the final feed formulation. Both pure iodine KI and Nal samples contain iodine which is 318 mg / ml and 345mg / ml respectively (FIG. 4). However, after spray drying the iodine content level decreases in both spray dried 10% KI and 10% Nal samples, equaling 233 mg / ml and 306 mg / ml respectively. Spray dried 10% KI sample contains less iodine compared to spray dried 10% Nal sample. However, the concentration of the Nal was increased to 12% after ICP-MS analysis. All the iodine samples also contain a very small amount of Na, K (Table 12).
[0087] Pure KI and Pure Nal sample can be spray dried. However, both the spray dried samples contain Na and K besides I2. The explanation is that both spray dried sample formulation contains four different organic fruit juices, so there is a possibility that the small amount of K and Na that is detected is from the fruit juice samples.Table 12: ICP-MS Analysis of the Pure Iodine Sample and Spray Dried PowderEXAMPLE 11 : Rheological Property Analysis
[0088] The viscosity of the spray-dried powder was determined using Anton-Paar MCR-302 rheometer at 25 °C room temperature with a cone on plate system. Distilled water was used as a control sample to compare with the reconstituted spray-dried powder and determine the initial test parameter of the rheometer (Alatalo & Hassanipour, 2020). A cone on a plate with 25 mm diameter and 1° angle of the cone on a flat surface of the plate was used to determine the viscosity. About 0.7 ml of liquid sample was placed on the plate carefully using a micropipette, and approximately 0.2 to 0.3 ml of liquid sample was trimmed from the plate while taking the data (Singh et al., 2022). It took about 8 to 9 minutes to give one data point for the system. Newtonian regression model and low viscosity range were selected as the fluid's flow behavior, which was consistent with the change in shear rate (s-1). 0.6 g spray-dried powder was reconstituted with 1 ml of DI water (control) and compared with plain distilled water. All the data was taken four times, and the pre-shear rate 0.1 to 100 s-1for an individual sweep was selected.EXAMPLE 12: Morphological Characterization Analysis Using SEM-EDX
[0089] A scanning electron microscope (SEM) equipped with an energy-dispersive X- ray system (EDX) (FEI Quanta 600F ESEM, Oregon, USA) and running in high vacuum was used to investigate the particle morphology of the spray-dried powders. For imaging, 25 nm Pt was sputtered on the samples after mounting them with carbon glue. Spot size 3.5, 30pm objective aperture, 5 kV, and an 8 mm working distance were used for the morphological study. EDX analysis was conducted to confirm the presence of K, Na, and I2 ions.
[0090] The viscosity of fluid food is a crucial characteristic with numerous uses in thefield of food technology, including the design of food processes and processing machinery, the regulation of products, filters, and mixers, the assessment of product quality, and the comprehension of the structure of food and agricultural raw materials (Magerramov et al., 2007). Numerous factors, such as temperature, molecule concentration, shape, and applied shear force, have an impact on fluid viscosity (Alatalo & Hassanipour, 2020). All the experiments were conducted at room temperature (25 °C), and the viscosity of DI water was 0.9101 mPa s which was used as a control sample. Both the spray dried reconstituted powders demonstrate the Newtonian behavior with intensification in shear rate and is calculated by regression equation. The viscosity of the 10% KI sample was found 1.89±0.1 mPa s whereas the viscosity of the 12 % Nal sample was found to be 1.58±0.03 mPa s (FIG. 5). The viscosity for spray dried 10% KI was higher compared to the spray dried 12 % Nal powder, as the amount of elderberry juice concentration was higher in the feed solution for the 10% KI formulation. Previous research also suggests that viscosity increases with increasing soluble solid content. Similar results were found by Sun-Waterhouse & Waterhouse with spray dried green kiwifruit juice milk powder and gold kiwifruit juice milk powder, where the green kiwifruit juice milk has higher viscosity in water as it contains higher soluble solids compared to the gold kiwifruit juice milk powder. Therefore, it is understandable that the reconstituted spray dried 10% KI has a higher viscosity. The data collected here suggest that spray dried iodine powder with lower juice concentration shows more easily flowable behavior.
[0091] The size and form of powder particles, which together determine their morphology, greatly affect the flow behavior of powder. The SEM images of pure iodine powders and spray-dried powders were collected at different magnifications to visualize the aggregation and surface morphology. FIGS. 6A-6D depict a substantial difference between the morphology of spray-dried iodine powder and pure iodine powders. The pure KI powder has a smoother surface compared to the pure Nal powder. However, spray- dried 10% KI is agglomerated and spherical in shape, this could be due to the interaction of the protein as the final formulations contain organic fruit juices. Spray-dried 12% Nal looks more crystallized compared to the spray-dried 10% KI powder. The thickness of the nozzle's aperture, which was maintained at 150 jxm throughout the drying process and drying rate, variation of the drying time determines the size of spray-dried powderparticles. For instance, smaller particles have a higher initial heat and mass transfer coefficient, which causes them to evaporate quickly. This is why smaller particles appear different from larger particles.EXAMPLE 13: Radiodensity Analyses
[0092] Bench testing revealed the viscosity (1.5 cP) and density (1 .35 g / mL) of the thin liquid EcoTrast-GI formulation resembles water, is non-ionic (readily goes into / stays in solution when mixed with water), has a radiodensity of ~30 mean gray scale (equivalent to barium sulfate and iohexol), and a pH equivalent to barium sulfate (~5.4). FIG. 7 shows a comparison of the radiodensity of the food based contrast agent 100, barium sulfate 300, and iohexol 400. Following tracheal instillation in rats, barium remained visible in the lungs and caused an inflammatory response (neutrophilic, macrophagic, and lymphocytic infiltrates); neither of these findings were appreciated in the iohexol and EcoTrast-GI groups. Thus, EcoTrast-GI appears to be as safe as iohexol and much safer than barium relative to the lungs.
[0093] Bench testing results revealed that a thin liquid formulation (i.e., not yet optimized for taste) contains less iodine (~320 mg / mL iodine) than FDA-approved iohexol 350 (i.e., 350 mg / mL iodine) and has a viscosity of 1 .5 cP and density of 1 .35 g / mL, which resembles water and is much thinner than both barium sulfate and iohexol. Moreover, the thin liquid formulation is non-ionic (i.e., does not dissociate into ions) and therefore readily goes into (and stays in) solution when mixed with water - in this respect, it is more similar to iohexol than barium. The radiodensity (mean gray scale) of the thin liquid formulation is ~30 (where 0 = dark / black and 255 = light / white), which is equivalent or slightly darker than barium sulfate and iohexol. Finally, the pH is equivalent to barium sulfate (~5.4) but lower than iohexol (~7.0). These collective results demonstrate that the food-based contrast agent is a stable, water-soluble oral contrast agent with equivalent contrast density and comparable pH to the two leading contrast agents used in VFSS (i.e., barium sulfate and iohexol), but with the added value of a lower viscosity and density resembling water.EXAMPLE 14: Statistical Analysis
[0094] Using the statistical tool JMP 14.0 (SAS Institute Inc, Cary, NC), analysis of variance (ANOVA) of mean values was performed. The Tukey test was used to compare the means, and significance was accepted at a 95% confidence level (p <0.05). The outcomes were shown as mean standard deviation.
Claims
ClaimsWhat is claimed is:1 . A food-based contrast agent formulation comprising a concentration of iodine salt encapsulated in a food grade carrier matrix, wherein the food-based contrast agent formulation is a free-flowing powder.
2. The formulation of Claim 1 , wherein the food grade carrier matrix is derived from at least one fruit, at least one vegetable, or at least one fruit and at least one vegetable.
3. The formulation of Claim 2, wherein the at least one fruit includes fruits selected from the group consisting of strawberry, blueberry, blackberry, grapefruit, cantaloupe, papaya, date, elderberry, guava, apple, pomegranate, pear, tomato, and any combination whereof.
4. The formulation of Claim 2, wherein the at least one vegetable includes vegetables selected from the group consisting of beets, potato, sweet potato, bell pepper, carrot, cucumber, squash, lettuce, sweet corn, and any combination thereof.
5. The formulation of Claim 1 , wherein the concentration of iodine salt is between 1 % and 50% of the formulation.
6. The formulation of Claim 5, wherein the concentration of iodine salt is between 5.0% and 15.0% of the formulation.
7. The formulation of Claim 1 , wherein the concentration of iodine salt comprises one or more iodine salts selected from the group consisting of sodium iodide, potassium iodide, and any combination thereof.
8. The formulation of Claim 1 , wherein the food grade carrier matrix comprises a fruit juice and a drying aid.
9. The formulation of Claim 8, further comprising a sweetener.
10. The formulation of Claim 8, further comprising an acid.11 . The formulation of Claim 8, further comprising a bitter blocker.
12. The formulation of Claim 9, wherein the sweetener is selected from the group consisting of sucrose, xylitol, maltose, aspartame, sucralose, coconut sugar, honey, vanilla, stevia, monk fruit sweetener, raisin, and any combination thereof.3713. The formulation of Claim 8, wherein the fruit juice is a juice derived from a fruit selected from the group consisting of strawberry, blueberry, blackberry, grapefruit, cantaloupe, papaya, date, elderberry, guava, apple, pomegranate, pear and any combination thereof.
14. The formulation of Claim 8, wherein the drying aid is selected from the group consisting of maltodextrin, gum Arabic, whey protein isolate, plant protein isolate, and any combination thereof.
15. The formulation of Claim 11 , wherein the bitter blocker is selected from the group consisting of beta-cyclodextrin, adenosine 5’ monophosphate, and any combination thereof.
16. The formulation of Claim 10, wherein the acid is an organic acid.
17. The formulation of Claim 16, wherein the organic acid is selected from the group consisting of citric acid, malic acid, ascorbic acid, and any combination thereof.
18. The formulation of Claim 1 , wherein the pH of the food-based contrast agent formulation is between 4 and 7.
19. The formulation of Claim 1 having a sweetness between 4° and 90° on the Brix scale.
20. A method of preparing a food-based contrast agent comprising: a. blending a quantity of at least one fruit to obtain a food grade carrier matrix; b. mixing an iodine salt with the food grade carrier matrix and water to produce a liquid feed; c. encapsulating the iodine salt in the food grade carrier matrix by drying the liquid feed to obtain a food-based contrast agent.21 . The method of Claim 20, wherein each fruit of the at least one fruit is independently selected from the group consisting of blueberry, strawberry, elderberry, cantaloupe, apple, guava, papaya, pear, pomegranate, date, and any combination thereof.
22. The method of Claim 20, wherein at least 10% of the liquid feed is the iodine salt, at least 60% of the liquid feed is the food grade carrier matrix, and at least 20% of the blended fruit is added water.3823. The method of Claim 20, wherein less than 12% of the liquid feed is the iodine salt, less than 40% of the liquid feed is the food grade carrier matrix, and less than 60% of the liquid feed is added water.
24. A liquid feed for generating a food based contrast agent, the liquid feed comprising: a. a concentration of iodine salt; b. a food grade carrier matrix; and c. a volume of water.
25. The liquid feed of Claim 24 wherein the viscosity of the liquid feed is between 1 mPa.s and 250,000 mPa.s.
26. The liquid feed of Claim 24 wherein the viscosity of the liquid feed is between 1 .0 mPa.s and 2.0 mPa.s.