Softgel capsules having a fill composition comprising magnesium oxide

Abstract

The softgel capsules have a fill composition that administers a 200-500 mg dose of magnesium from magnesium oxide, and an outer softgel gelatin shell. The composition includes 55-70 w / w% edible oil, 2-8 w / w% polysorbate 80, 0.5-2 w / w% hydrophobic silica, and 0.2-4 w / w% chelating agent to bind magnesium. The softgel capsules meet USP FDA requirements greater than NLT 75%(Q). <711> It has dissolution by.

Description

[Technical field]

[0001] The present disclosure relates generally to the field of softgel capsules, and more particularly to softgel capsules filled with magnesium oxide in edible oil with polysorbate 80, hydrophobic silica, and a chelating agent. The softgel capsules are formulated according to the USP monograph for magnesium oxide capsules. <711> Passes the dissolution test. [Background technology]

[0002] Many Americans do not get enough magnesium in their diet. Magnesium is available in nuts, seeds, whole grains, legumes, leafy vegetables, milk, yogurt, and fortified foods. However, some people turn to supplements to ensure they get their daily dose of magnesium. Magnesium can support muscle and nerve function, support energy production, improve sleep, and reduce anxiety and constipation. Although low magnesium levels do not typically have negative health consequences, chronically low levels may increase the risk of high blood pressure, heart disease, type 2 diabetes, and osteoporosis.

[0003] Many supplements for magnesium intake are available. The supplements can be in the form of powder, liquid, tablet, or hard capsule, and often contain a mixture of magnesium salts such as magnesium glycinate, magnesium citrate, magnesium chloride, magnesium sulfate, magnesium malate, and magnesium oxide. These magnesium salts differ in terms of solubility. For example, organic salts such as magnesium citrate and magnesium glycinate have been shown to have higher water solubility than magnesium oxide (MgO).

[0004] Magnesium oxide is an inorganic salt of magnesium. Magnesium oxide is of interest because it offers a higher loading of elemental magnesium. However, magnesium oxide suffers from limited bioavailability due to its low solubility. Referring to Figure 1, two two-piece hard capsules were filled with MgO and dissolution studies were performed. Hard capsule A was filled with approximately 350 mg of magnesium (approximately 620 mg MgO), HA grade Dead Sea Periclase. Hard capsule B was filled with approximately 350 mg of magnesium (approximately 620 mg MgO), heavy powder "LL" from Tomita Pharma. Dissolution studies were performed according to USP <711> The assay was performed according to the test procedure of USP 2001, which utilizes Apparatus 1 (basket apparatus) and Apparatus 2 (paddle apparatus) containing 900 ml of 0.1 N HCl and operating at 100 rpm for 45 minutes. The amount of dissolved MgO is determined using atomic absorption (AA) spectrophotometry at a wavelength of 285.2 nm using a filtered portion of the solution under test diluted with dissolution medium. A standard curve is constructed using magnesium standard solutions of known concentration in the same medium. The assay test for magnesium was performed according to the current USP monograph for magnesium oxide capsules. An acceptable result is equal to or greater than 75% (Q) of the labeled amount (NLT) of MgO dissolved. Both hard capsules A and B had approximately 44% dissolution, which is well below the acceptable result of 75%.

[0005] Two commercial products of magnesium softgels, magnesium citrate 125 mg and magnesium oxide softgel 400 mg, were also tested for dissolution using both the basket and paddle apparatus. The results of the tests are shown in Figures 2 and 3. Magnesium citrate is known to be more water soluble compared to the magnesium oxide form. Both products did not dissolve magnesium ions in dissolution tests using either the basket or paddle apparatus.

[0006] Both hard and soft gel capsules can be administered orally. Hard capsules are more stable and less susceptible to reactions with the shell matrix than soft gelatin capsules because they are made with unplasticized or low-plasticized gelatin and water to form a hard capsule that is typically filled with either powder or liquid.

[0007] Softgel capsules are more desirable than hard capsules due to consumer preference, improved bioavailability, speed of production, improved drug stability due to reduced exposure of the active ingredient to oxygen, uniformity of dosage, and product identification by capsule color and shape. Applicant hopes to encapsulate magnesium oxide in softgel capsules to obtain these advantages. However, preliminary dissolution testing of softgel capsules filled with magnesium oxide (MgO) has demonstrated low solubility and cross-linking. Softgel capsule shells contain significant amounts of water, and MgO may react with water from the shell, especially under high temperature and humidity, to form Mg(OH)2, which is less water soluble and extends dissolution time. Additionally, high temperature and humidity may promote cross-linking of the capsule shell resulting from gelatin polymerization, which may significantly slow the dissolution rate.

[0008] The applicant is a U.S.P. <711> I am not aware of any softgel capsules that have magnesium from magnesium oxide in a quantity sufficient to provide a daily dose of magnesium in one capsule that meet or exceed the dissolution tests and the following USP monographs for magnesium oxide capsules:

[0009] High magnesium loading provided by magnesium oxide and USP <711> There is a need for an orally administrable soft gel capsule for individuals needing a magnesium supplement that has magnesium oxide dissolution that passes testing. Summary of the Invention

[0010] In all embodiments, disclosed herein is a softgel capsule having a fill composition delivering a 200-500 mg dose of magnesium from magnesium oxide and an outer softgel gelatin shell. The composition comprises 55-70 w / w% edible oil, 2-8 w / w% polysorbate 80, 0.5-2 w / w% hydrophobic silica, and 0.2-4 w / w% chelating agent to bind magnesium. The softgel capsule is formulated to meet USP FDA requirements of greater than NLT 75%(Q), more preferably greater than NLT 85%(Q). <711> The chelating agent may be an ethylenediaminetetraacetic acid (EDTA) salt and / or a weak acid. When the weak acid is present, it is selected from the group consisting of ascorbic acid, aspartic acid, citric acid, glutamic acid, pyridoxine HCl, and combinations thereof. In one embodiment, the chelating agent comprises an ethylenediaminetetraacetic acid (EDTA) salt and a weak acid in a ratio of 2:1 to 2.5:1. Polysorbate 80 may be present as about 6% to about 6.7 w / w% of the filler composition.

[0011] In an exemplary embodiment, the edible oil comprises a medium chain triglyceride oil, and the fill composition can have a formulation of 50-65 w / w% medium chain triglyceride oil; 5.8-6.8 w / w% polysorbate 80; 1-2 w / w% hydrophobic silica; and 0.5-4 w / w% chelating agent to bind magnesium. The softgel capsules are formulated according to USP <711> Dissolution by the accelerated condition chamber after 3 months at 30° C. / 65% RH and after 1 month at 40° C. and 75% relative humidity is greater than NLT 75% (Q), and after 6 months at ambient conditions is greater than NLT 85% (Q). <711> Dissolution by is greater than NLT 100% (Q) after 6 months at ambient conditions and 3 months at an intermediate set at 30° C. / 65% RH, and greater than NLT 75% after 4 months at an accelerated condition chamber set at 40° C. and 75% relative humidity. This exemplary embodiment can have a chelating agent comprising an ethylenediaminetetraacetic acid (EDTA) salt and / or a weak acid. The weak acid can be selected from the group consisting of ascorbic acid, aspartic acid, citric acid, glutamic acid, pyridoxine HCl, and combinations thereof. Additionally, the chelating agent can include an ethylenediaminetetraacetic acid (EDTA) salt and a weak acid in a ratio of 2:1 to 3:1. [Brief description of the drawings]

[0012] [Figure 1] 1 is a schematic flow chart of images from dissolution testing of magnesium oxide (MgO) filled two-piece hard capsules.

[0013] [Diagram 2] 1 is a chart of images and data from a dissolution study using a basket apparatus for 125 mg of magnesium from magnesium citrate softgel and 400 mg of magnesium from MgO in a softgel capsule.

[0014] [Diagram 3]1 is a chart of images and data from dissolution testing using a commercial paddle apparatus for 125 mg of magnesium from magnesium citrate softgel and 400 mg of magnesium from MgO in a softgel capsule.

[0015] [Figure 4] 1 is a chart of images and data from a dissolution study of 400 mg of magnesium from MgO in a softgel capsule.

[0016] [Diagram 5] 13 is a chart of images and data from a dissolution study of 400 mg of Magnesium from MgO in softgel capsules for prototypes 5-18.

[0017] [Figure 6] 13 is a chart of images and initial test data from dissolution testing of 400 mg of Magnesium from MgO in softgel capsules for prototypes 20, 21, and 22.

[0018] [Figure 7] 13 is a chart of dissolution testing images and stability data using a basket apparatus for prototype 20 from 3 months, 4 months, and 6 months at ambient conditions.

[0019] [Figure 8] 8 is a stability plot of the data from FIG. 7 for prototype 20.

[0020] [Figure 9] 13 is a chart of dissolution testing images and stability data using a basket apparatus for prototype 21 from 3 months, 4 months, and 6 months at ambient conditions.

[0021] [Figure 10] 10 is a stability plot of the data from FIG. 9 for prototype 21.

[0022] [Figure 11] 13 shows images and stability data charts from dissolution testing using a basket apparatus for prototype 21 from 1 month, 2 months, and 3 months at intermediate conditions (30° C. / 65% RH).

[0023] [Figure 12] 12 is a stability plot of the data from FIG. 11 for prototype 21.

[0024] [Figure 13] 13 is a chart of dissolution testing images using a paddle apparatus and stability data for prototype 20 from 4 months and 6 months at ambient conditions.

[0025] [Figure 14] 13 is a chart of dissolution testing images using a paddle apparatus and stability data for prototype 21 from 4 months and 6 months at ambient conditions.

[0026] [Figure 15] 13 is a stability plot of 5-month stability data for prototype 21 under accelerated conditions using a paddle apparatus dissolution test.

[0027] [Figure 16] 1 is a bar graph of the effect of storage conditions on MgO dissolution profile in a paddle apparatus during a 6-month stability study. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] Ranges can be expressed herein as from "about" one particular value and / or to "about" another particular value. As used herein, "about" means ±5%, or more preferably ±2% of the numerical value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values ​​are expressed as approximations, using the antecedent "about," it will be understood that the particular value forms another embodiment. Moreover, it will be understood that the endpoints of each range are significant in relation to the other endpoint, as well as independently of the other endpoint. Concentration percentages are typically weight / weight % unless otherwise specified.

[0029] The following description and drawings are illustrative and should not be construed as limiting. Numerous specific details are described to provide a thorough understanding of the present disclosure. However, in some cases, well-known or conventional details are not described to avoid obscuring the description. Reference to an "embodiment" or an "exemplary embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure.

[0030] USP <711> Provided herein is a softgel capsule filled with magnesium oxide in an edible oil containing polysorbate 80, hydrophobic silica, and a chelating agent enclosed within an outer softgel shell that passes dissolution testing at 75% NLT of labeled claim. The softgel capsule has 400 mg of magnesium from MgO.

[0031] As used herein, a "softgel capsule" refers to a pharmaceutical device having a shell formed of a highly plasticized soft elastic shell material to define at least one chamber for a dose of fill material. The fill material may be a liquid, a powder suspended in a liquid, or a semi-solid. A softgel capsule may be seamed or seamless, depending on the manufacturing method. Seamed softgel capsules can be made using a rotary die encapsulation machine. Seamless softgel capsules can be made by coacervation or by the "dropping process" (i.e., a coextrusion process without mechanical shaping) using a concentric nozzle. The shell material may be animal gelatin plasticized with a polyhydric alcohol (e.g., glycerol, sorbitol, maltitol, etc.), or one or more vegetable capsule-forming materials, such as starch, modified starch, carrageenan, and alginate, or similar polymers with or without a polyhydric alcohol plasticizer. Any softgel shell material is suitable herein. Examples of soft gel shells are described in U.S. Pat. No. 5,614,217, U.S. Pat. No. 7,807,194, U.S. Patent Application Publication No. 2005 / 0152969, and U.S. Patent Publication No. 2019 / 0269623, the contents of each of which are incorporated by reference in their entirety.

[0032] Softgel capsules can offer distinct advantages over more traditional dosage forms such as tablets, hard shell capsules, and liquids. These advantages include patient compliance and consumer preference, improved bioavailability, faster product development in many cases, reduced manufacturing time, improved drug stability due to reduced exposure of the active ingredient to oxygen, uniformity of dosage, and product differentiation due to, for example, a novel shape.

[0033] The filler composition comprises 55-70 w / w% edible oil, 2-8 w / w% polysorbate 80, 0.5-2 w / w% hydrophobic silica, and optionally 0.2-4 w / w% chelating agent for binding magnesium. When the chelating agent is present, higher dissolution rates are achieved, especially at high magnesium amounts. The polysorbate may more preferably be in the range of about 6% to about 6.7 w / w% of the filler composition. In one embodiment, the filler composition comprises 50-65 w / w% edible oil, 5.8-6.8 w / w% polysorbate 80, and 0.5-4 w / w% chelating agent for binding magnesium.

[0034] One example of an edible oil is medium chain triglyceride (MCT) oil. MCT oil is a triglyceride containing two or three fatty acids, i.e., medium chain fatty acids, with an aliphatic tail of 6 to 12 carbon atoms. In one embodiment, MCT oil may be derived from palm kernel oil and / or coconut oil. Typically, MCT oil is separated from coconut or palm kernel oil by a process called fractionation. Any other edible oil may be used alone or in combination with MCT oil. Some examples of sources of fats and oils may include any fraction of coconut oil, palm kernel oil, palm oil, fish oil, lard, tallow oil, butterfat, soybean oil, safflower oil, cottonseed oil, rapeseed oil, poppy seed oil, corn oil, sunflower oil, olive oil, algae oil and blends thereof. Hydrogenation can be used to modify the degree of unsaturation of the fatty acids, thereby modifying the fatty acid composition.

[0035] Hydrophobic silica is a form of silicon dioxide with hydrophobic groups chemically bonded to the surface. The hydrophobic groups are usually alkyl or polydimethylsiloxane chains. Hydrophobic silica was chosen as an additive to make the entire filler matrix more hydrophobic and reduce the interaction between the filler and water in the shell. This minimizes the reaction between shell moisture and magnesium oxide and inhibits the formation of magnesium hydroxide.

[0036] The chelating agent includes ethylenediaminetetraacetic acid (EDTA) salts and / or one or more weak acids. EDTA is a chelating agent and sequestering agent that inhibits undesired reactions in the filler matrix. EDTA reacts with magnesium to form a complex with magnesium ions, which is a stable water-soluble complex. The resulting (chelated) structure immobilizes the magnesium ions and prevents them from reacting with other components in the filler matrix and shell matrix, especially water. Explained another way, the magnesium ions are captured by the chelating agent before being loaded or encapsulated in the softgel, thereby inhibiting the hydration of magnesium oxide.

[0037] The chelating agent binds magnesium ions from the MgO to prevent the MgO from reacting with water to form magnesium hydroxide. Examples of EDTA salts include, but are not limited to, calcium disodium EDTA, diammonium EDTA, dipotassium EDTA, disodium EDTA, TEA-EDTA, tetrasodium EDTA, tripotassium EDTA, and trisodium EDTA. In all embodiments, the chelating agent can include an EDTA salt and a weak acid. The weak acid is selected from the group consisting of ascorbic acid, aspartic acid, citric acid, glutamic acid, pyridoxine HCl, and combinations thereof.

[0038] The present invention will now be described in detail with reference to the following examples, it being understood that one, some or all of the features of the various embodiments and examples described herein may be combined to form other embodiments.

[0039] example Dissolution of magnesium oxide was tested using hard capsules as described in the Background section to establish a baseline for MgO dissolution. In all of the following examples, conventional mixing techniques were used to prepare hand-filled capsules for these preliminary tests. Prototype softgel capsules were prepared using air-filled softgel capsules with shells of 150 Bl bovine bone gelatin plasticized at 55% with glycerin. Each moist air-filled capsule was injected with a known weight of one of the fill materials described in the following examples. The open tip of each of the filled softgel capsules was then sealed by heating. The capsules were dried for 2-3 days in an R&D drying chamber set at 10-20% relative humidity. They were then dried using a USP drying method using a basket apparatus. <711> A dissolution test was carried out.

[0040] 400 mg of Magnesium from MgO Softgel Capsules

[0041] Next, a known fill material of MCT oil as the primary delivery vehicle and rapeseed lecithin was used as an emulsifier for magnesium oxide in a softgel capsule. This softgel capsule had a dissolution test result of 0.02% and became the control formulation shown in Figure 4. Due to this poor performance of this base fill material, other base fill materials were selected for trials 1-3, and polysorbate 80 was selected as the emulsifier instead of using lecithin. The primary fill material used was MCT oil in trials 1 and 2, and polyethylene glycol 400 in trials 3 and 4. [Table 1]

[0042] The dissolution test results for Prototypes 1-4 are shown in Table 1. Prototypes 1 and 2 with polysorbate 80 and MCT oil had a dissolution of about 29%, which is much better than the 0.02% for the control formulation, but still did not meet the USP <711> The NLT of 75% (Q) was still far short of meeting the NLT of 75%. The hydrophilic PEG 400 base filler with or without polysorbate 80 had only about 8-9% dissolution.

[0043] Improves dissolution of 400 mg of magnesium from MgO in a base fill of polysorbate 80 / MCT oil.

[0044] EDTA was added as a chelating agent to help prevent magnesium insolubility by binding to magnesium and preventing hydration to form magnesium hydroxide as described herein. Various weak acids were tested to see if they would improve dissolution. Citric acid, ascorbic acid, and pyridoxine hydrochloride were selected to increase magnesium solubility. Hydrophobic silica was added as a suspending agent and additive to form a layer between the shell and the filler composition to minimize water migration and reduce hydration of magnesium oxide.

[0045] [Table 2]

[0046] Based on the results of the dissolution test ("AA"), compared to Table 1, the addition of hydrophobic silica and EDTA / citric acid chelating agent improved the dissolution test results. <711> In the dissolution tests, the rates improved by at least 15%, 20%, and 30%, but none of the softgel capsules passed. Prototype 7 with ascorbic acid had the lowest dissolution rate, while Prototype 11 with hydrophobic silica and vitamin B6 had the highest dissolution rate. Based on these results, more prototypes were made.

[0047] [Table 3]

[0048] Based on the test results of prototypes 12-18, it was concluded that increases in polysorbate 80 and pyridoxine HCl enhanced solubility, and hydrophobic silica was adjusted to enhance solubility.

[0049] Prototype 19 presented below is a modified formulation from Prototype 18 by adjusting the amount of MCT oil to fit one softgel. Test results met the NLT 75% requirement.

[0050] [Table 4]

[0051] Due to the success of 400 mg of magnesium from an MgO softgel capsule in trial run 19, a pilot batch was manufactured for stability studies.

[0052] Pilot Batch: 400 mg Magnesium from MgO Softgel Capsules

[0053] These pilot batches used the gelatin and veggie softgel capsules described above. Each capsule was a rectangular capsule size 25. The formulations selected for the pilot batches are outlined in Table 5 and were made using conventional techniques. [Table 5]

[0054] Prototype 22 failed the dissolution test. Here, the veggie softgel capsules were dissolved in water using Apparatus 1 in a USP <711> The test medium remained generally clear, with only partial dissolution during the 45 minute test period defined by , and Prototypes 20 and 21 passed the dissolution test. Prototype 20 had an average dissolution of 97.5% (103.9%; 91.1%; 87.7%; 108.2%; 112.0%; 82.3%). Prototype 21 had an average dissolution of 86.7% (89.9%; 90.0%; 92.6%; 85.8%; 85.0%; 76.7%).

[0055] Ambient Bulk Stability Testing of Prototypes 21 and 22

[0056] The capsules were packed into polyethylene bags, sealed with cable ties, placed in single-walled cardboard boxes and stored at ambient conditions.

[0057] Dissolution data from Samples 20 and 21, shown below in Tables 6 and 7, were obtained using the USP 100001 standard using the basket and paddle apparatus, respectively. <711> This concerns bulk stability at ambient conditions. [Table 6] [Table 7]

[0058] Prototype 20 capsules showed a significant decrease in dissolution between 4 and 6 months in the basket device, decreasing from 94.3% to 43.5%. Results were 112.5% ​​at 4 months and 79.8% at 6 months with the basket device.

[0059] Prototype 21 capsules were relatively stable over the 6-month stability period, with 3-, 4-, and 6-month results of 86.7%, 88.9%, and 83.5% for the basket device, and 108.9% at 3 months and 108.4% at 4 months for the paddle device.

[0060] Bottle stability under controlled conditions for prototypes 20 and 21

[0061] Forty-five capsules from Trial 20 and Trial 21 were placed in white HDPE bottles, sealed by heat induction, and stored at three storage conditions for stability: 25°C / 60% relative humidity (RH) (real-time), 30°C / 65% RH (intermediate), and 40°C / 75% RH (accelerated). <711> Samples were tested for dissolution by ethanol for a period of three months.

[0062] [Table 8]

[0063] [Table 9]

[0064] [Table 10]

[0065] [Table 11]

[0066] Prototype 21 had an NLT of 80% at ambient conditions using Apparatus 1 (basket) without showing any significant decrease in dissolution over 6 months of bulk stability.

[0067] Prototype 21 met the requirements for bulk stability at ambient conditions for 6 months at over 100% using Apparatus 2 (paddles).

[0068] Prototype 20 failed to meet requirements after one month at intermediate and accelerated conditions.

[0069] Prototype 21 met the NLT 75% requirement for 3 months at real-time and intermediate conditions using Apparatus 1 (basket) and also met the requirement with NLT 100% dissolution using Apparatus 2 (paddle) method from the same conditions.

[0070] Prototype 21 met the NLT 75% requirement using the basket apparatus for one month at accelerated conditions and using the paddle apparatus for a four month period at accelerated conditions.

[0071] Although the examples are based on achieving the dosage of magnesium from MgO, the filler composition can include additional sources of magnesium, such as magnesium glycinate, magnesium citrate, magnesium chloride, magnesium sulfate, magnesium malate, etc., as sources of magnesium beyond the dosage from MgO.

[0072] Methods of Treating a Subject in Need of Magnesium Supplements

[0073] As used herein, "subject" refers to a vertebrate, more specifically a mammal, such as a human (or individual) who is in need of a supplement to his or her diet, particularly a magnesium supplement. Methods for treating an individual in need of a magnesium supplement include identifying such an individual and administering magnesium supplements to such an individual as described in the USP <711> The method includes administering one softgel capsule having 400 mg of magnesium from magnesium oxide that has passed the dissolution test according to the method described herein. Numerous examples of softgel capsules having suitable filler compositions are described herein and can be administered as a daily dose. The daily dose can be taken by the individual for several days, several weeks, several months, or for the rest of their life. Identifying an individual in need of magnesium supplements can include a medical professional testing the individual for magnesium deficiency and determining that such a deficiency exists.

[0074] The above detailed description of the embodiments of the present disclosure is not intended to be exhaustive or to limit the teachings to the precise form disclosed above. Although specific embodiments and examples of the present disclosure have been described above for illustrative purposes, various equivalent modifications are possible within the scope of the present disclosure, as one of ordinary skill in the art will recognize and appreciate. For example, while a process may be presented in a given order, alternative embodiments may implement practices having steps in a different order, and some steps may be deleted, moved, added, subdivided, combined, and / or modified to provide alternative or subcombinations. Each of these processes may be implemented in a wide variety of ways, as one of ordinary skill in the art will appreciate. Also, while processes are sometimes shown to be performed sequentially, these processes may instead be performed in parallel or at different times. Furthermore, any specific numbers described herein are merely examples, and alternative implementations may use different values ​​or ranges.

[0075] The teachings of the disclosure provided herein can be applied to other systems, not necessarily the systems described above. The elements and operations of the various embodiments described above can be combined to provide further embodiments. For example, the above patents incorporated herein by reference can be modified as necessary to provide further embodiments of the disclosure provided herein. Furthermore, while the above description describes specific embodiments, no matter how detailed the above content is described, the teachings can be implemented in many ways that will be understood by those skilled in the art. The details of the capsule members, capsules, and related processes and products may vary considerably in their implementation details, but are still encompassed by the subject matter disclosed herein. Thus, while exemplary embodiments of the present invention have been shown and described, it should be understood that all terms used herein are descriptive rather than limiting, and that many changes, modifications, and substitutions may be made by one skilled in the art without departing from the spirit and scope of the following claims.

Claims

1. Magnesium in doses of 200-500 mg from magnesium oxide; Edible oil with a wt / w% content of 48-70%; 2-8 w / w% polysorbate 80; 0.5–2 w / w% hydrophobic silica; and A chelating agent of 0.2–4 w / w% for binding to magnesium; A filler composition containing, A soft gel gelatin shell that encloses the filling material on the outside, Includes, Softgel capsules having a USP<711> dissolution rate of 75% or more of the labeled MgO solubility (NLT).

2. The soft gel capsule according to claim 1, wherein the chelating agent comprises an ethylenediaminetetraacetic acid (EDTA) salt and / or a weak acid.

3. The softgel capsule according to claim 2, wherein the weak acid present is ascorbic acid, aspartic acid, citric acid, glutamic acid, and / or pyridoxine HCl.

4. The soft gel capsule according to claim 1, wherein the chelating agent comprises an ethylenediaminetetraacetic acid (EDTA) salt and a weak acid in a ratio of 2:1 to 2.5:

1.

5. The soft gel capsule according to claim 4, wherein polysorbate 80 is present in the filler composition at an amount of about 6% to about 6.7 w / w%.

6. The softgel capsule according to claim 1, having dissolution by USP<711> greater than NLT 85% (Q).

7. The soft gel capsule according to claim 1, wherein the edible oil comprises medium-chain triglyceride oil.

8. The filler composition is 50-65 w / w% medium-chain triglyceride oil; 5.8–6.8 w / w% polysorbate 80; 1-2 w / w% hydrophobic silica; and It contains 0.5-4 w / w% of a chelating agent for binding to magnesium. The softgel capsule according to claim 7, having dissolution by USP<711> greater than NLT 75% (Q).

9. The softgel capsule according to claim 8, wherein dissolution by USP<711> using apparatus 1 is greater than NLT 85% (Q) after 6 months under ambient conditions, greater than NLT 75% after 3 months at intermediate conditions set to 30°C / 65% RH, and greater than NLT 75% after 1 month in an accelerated condition chamber set to 40°C and 75% relative humidity.

10. The softgel capsule according to claim 8, wherein dissolution by USP<711> using apparatus 2 is greater than NLT 100% (Q) after 6 months under ambient conditions and after 3 months at an intermediate setting of 30°C / 65% RH, and greater than NLT 75% after 4 months in an accelerated conditions chamber set at 40°C and 75% relative humidity.

11. The soft gel capsule according to claim 8, wherein the chelating agent comprises an ethylenediaminetetraacetic acid (EDTA) salt and / or a weak acid.

12. The softgel capsule according to claim 11, wherein the weak acid present is ascorbic acid, aspartic acid, citric acid, glutamic acid, and / or pyridoxine HCl.

13. The soft gel capsule according to claim 8, wherein the chelating agent comprises an ethylenediaminetetraacetic acid (EDTA) salt and a weak acid in a ratio of 2:1 to 3:1.

Images