Non-animal softgel capsule formulations, methods of preparation, and methods of use thereof

Abstract

To provide improved non-animal softgel capsule formulations that have shorter dissolution and / or disintegration times.SOLUTION: A shell composition is provided which has a non-animal derived gelling agent and a water-soluble polymer. The shell composition completely dissolves in less than 30 minutes when subject to a dissolution with a USP Apparatus II with paddles at 75 RPM in 900 ml of 0.1 N HCl and deionized water at 37°C. Also provided is a softgel composition comprising a fill material encapsulated within the shell composition.SELECTED DRAWING: None

Description

[Technical Field]

[0001] Related Applications This application was filed on October 9, 2019, which application is incorporated herein by reference in its entirety. This application claims priority to U.S. Provisional Patent Application No. 62 / 912,886, filed on 2004 / 01 / 14.

[0002] The present disclosure relates to non-animal softgel capsule formulations. Methods for preparing and using the same are also disclosed herein. [Background technology]

[0003] A solution or dispersion of a nutritional or pharmaceutical agent in a liquid carrier is encapsulated within a softgel capsule. It is important to note that compressed, coated, or uncoated solid It offers many advantages over other dosage forms such as solid tablets or bulk liquids. Such encapsulation of the dispersion is advantageous when relatively small amounts of active ingredient have to be administered. This allows for accurate delivery of the unit dose, which is particularly important. Furthermore, the solids are homogeneously mixed and compressed. in the tableting process where the tablet must be compressed or weighed before each oral administration. It is not possible to achieve uniformity in the delivery of the total dose of active ingredient to the bulk liquid carrier. It's more difficult.

[0004] In addition, soft gel capsules, most commonly soft gelatin capsules, are easy to swallow. and is more acceptable to patients because no taste masking is required to mask the unpleasant taste of the active agent. Softgel capsules provide an easy-to-use dosage form, allowing the required number of doses to be dispensed from the packaging. It is easier for patients to carry than bulk liquids because it only needs to be dispensed. There are also.

[0005] Softgel encapsulation of drugs may improve the bioavailability of pharmaceutical agents As soon as the capsule shell is ruptured, the active ingredient is rapidly released in liquid form. The complete disintegration of the capsule is not the same as in tableted compositions. is not essential for the active ingredient to be absorbable. Furthermore, it provides for more rapid absorption. Therefore, relatively insoluble active ingredients can be dispersed in a liquid carrier.

[0006] Soft candy made from animal-derived gelatin that takes between 5 and 15 minutes to burst. Compared to current non-animal softgels (e.g., Vegicaps (Trademark) and OptiShell® Softgels) remain in the dissolution medium until they burst. It takes between 20 and 40 minutes for immediate relief to be achieved. Such long dissolution times are necessary for the treatment of patients with steroids (analgesics, antihistamines / allergy medications). This can be a problem for some.

[0007] Therefore, improved non-animal based soft drinks with shorter dissolution and / or disintegration times are available. There is a need for a soft gel capsule formulation. Summary of the Invention [Means for solving the problem]

[0008] According to various embodiments, a softgel composition comprising a fill material encapsulated in a shell composition A shell comprising a non-animal derived gelling agent and a water-soluble polymer is disclosed herein. In certain embodiments, the shell composition is 900 mL of 0.1 N at 37° C. Dissolution tests in HCl and deionized water using USP Apparatus II with paddles at 75 RPM When tested, complete dissolution occurred in less than 30 minutes.

[0009] According to certain embodiments, a capsule containing an active agent or cosmetic agent and encapsulated by a shell composition. The softgel composition is disclosed to include a fill material containing carrageenan. a non-animal derived gelling agent comprising naan, starch, or a combination thereof, and polyvinyl alcohol; Alcohol, pullulan gum, polylactic acid, polyvinyl alcohol-polyethylene glycol RAFT copolymer, high molecular weight polyethylene glycol, povidone, surfactant, or The present invention also includes water-soluble polymers containing combinations of these.

[0010] Method for preparing a softgel composition comprising a non-animal derived gelling agent and a water-soluble polymer Various embodiments that do so are also disclosed herein.

[0011] According to a further embodiment, a filler material containing an active pharmaceutical agent (or cosmetic agent) is provided, the filler material being non-moving. A filling material encapsulated by a shell composition comprising a bio-derived gelling agent and a water-soluble polymer. Disclosed herein are softgel compositions comprising the same, as well as methods for making and processing the same. It is being done.

[0012] According to still further embodiments, the active agents or cosmetic agents described herein A condition treatable by administering any of the softgel compositions described herein to a patient. Disclosed herein are methods of treating a subject in need thereof by administering to said subject

[0013] The above and other features of the present disclosure, its nature and various advantages, are best understood from the following detailed description of the accompanying drawings. This will become apparent from consideration of the following detailed description, taken in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0014] [Figure 1] 1 illustrates the release profile of an active agent (e.g., ibuprofen) from a conventional non-gelatin capsule compared to a softgel capsule according to certain embodiments. The release profile is also illustrative of the dissolution profile of a conventional non-gelatin capsule shell composition compared to a softgel shell composition according to certain embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0015] softgel compositions, e.g., softgel capsule film compositions that encapsulate a fill material; Various embodiments relating to its preparation and methods of use are described herein. The invention is not limited to the details of construction or process steps set forth in the following description. It should be understood that the invention is capable of other embodiments and of various modifications. can be practiced or performed in a certain way.

[0016] Throughout this specification, the terms "one embodiment," "particular embodiment," "one or more embodiments," and "one or more embodiments" are used. References to an "embodiment" or "an embodiment" refer to the particular features described in connection with the embodiment. It is intended that the feature, structure, material, or characteristic be included in at least one embodiment of the present invention. For this reason, the term "one or more embodiments" is used in various places throughout this specification. "in a particular embodiment," "in one embodiment," or "in one embodiment" Appearances of phrases such as "in an embodiment" and "in an embodiment" do not necessarily refer to the same embodiment of the invention. Furthermore, any particular feature, structure, material, or characteristic may be incorporated into one or more embodiments. may be combined in any suitable manner.

[0017] As used herein, unless the context clearly indicates otherwise, the singular forms "a" and "an" are used interchangeably. , and "the" includes plural references. Thus, for example, a reference to "polymers" includes a single polymer as well as a mixture of two or more polymers.

[0018] As used herein, the term "about" in connection with a measured quantity means the quantity at which the measurement is made. , as would be expected by one skilled in the art using a level of care commensurate with the purpose of the measurement and the precision of the measurement equipment. In certain embodiments, "about" refers to normal variation in the measured quantity. The term includes the recited number plus or minus 10%, so that "about 10" includes 9 to 11. This becomes the case.

[0019] The term "at least about" in connection with a measured quantity is used to describe the quantity measured and the purpose and accuracy of the measurement. As would be expected by one skilled in the art using a level of care commensurate with the accuracy of the equipment and measurement. Refers to normal variations in the measured quantity and any quantities higher than that. In this context, the term "at least about" refers to the recited number minus 10% and higher. Any quantity, such that "at least about 10" includes 9 and any number greater than 9. This term may also be expressed as "about 10 or more." Similarly, "less than about" The term generally includes the recited number plus 10% and any lower quantity, resulting in Thus, "less than about 10" includes 11 and any number less than 11. It can also be expressed as "about 10 or less."

[0020] The term "immediate release" refers to the dosage forms disclosed herein (e.g., softgel capsules). Formulation) in 900 mL of 0.1 N HCl (optionally containing pepsin) at 37°C. In vivo dissolution in USP Apparatus II at approximately 50 RPM to approximately 250 RPM The amount of active agent (or cosmetic agent) encapsulated within the shell composition, as measured by at least about 85 wt.%, at least about 90 wt.%, or at least about 95 wt.% within about 30 minutes, within about 45 minutes, or within about 60 minutes.

[0021] The term "controlled release" refers to the dosage forms (e.g., softgel capsules) disclosed herein. formulations) over a period of time, for example to provide a once-daily or twice-daily dosage form. Therefore, it refers to a dosage form that releases an active pharmaceutical agent (or cosmetic agent) encapsulated within its shell composition. vinegar.

[0022] As used herein, the term "softgel" does not necessarily mean that gelatin is The shell composition (or film composition) and / or its fill material (or fill composition) In certain embodiments, the shell composition (or filler) is not meant to be part of the In other embodiments, the shell composition may comprise gelatin, but in other embodiments, the shell composition may comprise Similarly, in certain embodiments, the filler material (or filler The filler composition may include gelatin, although in other embodiments the filler material is The term "soft gel" is used throughout this description to refer to "soft gels." It may be used interchangeably with the term "shell."

[0023] The term "shell composition" is used throughout this description to refer to "film composition," "shell The terms "software", "software technology", and "film" may be used interchangeably. (For example, these terms refer to the outer portion of a soft gel composition that encapsulates a filler material.) (Refers to the shell of the gel capsule).

[0024] The term "fill material" is used throughout this description interchangeably with "fill composition" and "filler." These terms may be used interchangeably with the term "shell composition." The term "soft gel" refers to the interior of a soft gel composition (e.g., the interior of a soft gel capsule).

[0025] The term "softgel composition" is used throughout this description as "softgel formulation" and "softgel composition." It may be used interchangeably with the term "dosage form." In certain embodiments, "soft gel" refers to a The terms "soft gel composition" and "soft gel formulation" are used interchangeably. "softgel capsule composition" or "softgel capsule formulation" This may be done.

[0026] All parts and percentages are by weight unless otherwise indicated. If no weight percent (wt.%) is given, it is the weight percent of the entire composition excluding any volatile materials. based on dry solids.

[0027] The recitation of ranges of values ​​herein includes any value within that range unless otherwise indicated herein. It is only intended to serve as a shorthand way of referring individually to each value it contains. and each value is incorporated herein as if it were individually listed herein. Unless otherwise indicated herein or clearly contradicted by context, All methods described herein may be performed in any suitable order.

[0028] All examples or use of exemplary language (e.g., "such as") provided herein are intended to be illustrative and not restrictive. It is intended only to facilitate understanding of certain materials and methods and not to limit the scope. No language in the specification shall be construed as indispensable to the practice of the disclosed materials and methods. should not be construed as suggesting any element not claimed as such.

[0029] While the present disclosure refers to certain embodiments herein, it is understood that these embodiments include, but are not limited to, It is to be understood that these are merely illustrative of the principles and applications of the present invention. Various modifications and variations to the compositions and methods may be made without departing from the spirit and scope of the present invention. It will be apparent to one skilled in the art that various modifications and variations can be made to the present invention. The disclosure includes modifications and variations that come within the scope of the appended claims and their equivalents. It is intended to be

[0030] Softgel capsule formulation A softgel capsule shell composition comprising a non-animal derived gelling agent and a water soluble polymer, In certain embodiments, the shell composition has a viscosity of 900 psi at 37° C. 00 mL of 0.1 N HCl and deionized water, 50-250 RPM (e.g., 75 RPM) When subjected to dissolution in USP Apparatus II with paddles (PM), complete dissolution was achieved in less than 30 minutes. In certain embodiments, the softgel capsule shell composition is released in less than 25 minutes. , elute in less than 20 minutes, less than 15 minutes, less than 10 minutes, or less than 5 minutes.

[0031] In certain embodiments of the softgel capsule shell composition, a non-animal derived gelling agent Carrageenan and starch are included in the softgel capsule shell composition. The weight ratio of geenan to starch is, for example, about 1:1 to about 1:10, about 1:1 to about 1 :8, about 1:1 to about 1:5, or about 1:2.5 to about 1:4.5. In this embodiment, the inclusion of a water-soluble polymer in the softgel capsule shell composition This contributes to the weight ratio of lagenan to starch, which is This is less critical than if the water-soluble polymer described herein were not present in the composition. (e.g., for dissolution, disintegration, elasticity, strength, etc.).

[0032] A fill material comprising an active agent, encapsulated by a shell composition disclosed herein. Softgel capsule formulations containing fill materials such as The filling material may be, for example, a hydrophilic material, a lipophilic material, an amphiphilic material, or a combination thereof. The filler material may be in the form of a solution, suspension, or the like, together with an optional surfactant. The active agent (e.g., an active pharmaceutical ingredient or a nutritional supplement) may be a solid, semi-solid, or solid. It may further comprise a food supplement or cosmetic agent.

[0033] The shell compositions disclosed herein contain at least one of a buffer, a plasticizer, and water. The softgel capsule formulations described herein are vegetarian. and may be free of animal-derived materials such as gelatin. In some embodiments, the shell composition is less than 10 wt.%, less than 5 wt.%, or less than 1 wt.%. %, or 0 wt.% animal-derived gelling agent.

[0034] In certain embodiments, the shell compositions disclosed herein can be used in a volume of 900 mL at 37° C. in 0.1N HCl and deionized water (optionally containing pepsin) at approximately 50 RPM About 250 RPM (e.g., about 50 RPM, about 75 RPM, about 100 RPM, about 150 RPM) Dissolving by USP Apparatus II with paddles at 200 RPM, approximately 200 RPM, or approximately 250 RPM If served, it will be served in less than 25 minutes, less than 20 minutes, less than 15 minutes, less than 10 minutes, or less than 5 minutes. Dissolve completely.

[0035] In certain embodiments, the shell compositions disclosed herein can be used in a volume of 900 mL at 37° C. in 0.1N HCl and deionized water (optionally containing pepsin) at approximately 50 RPM About 250 RPM (e.g., about 50 RPM, about 75 RPM, about 100 RPM, about 150 RPM) Dissolving by USP Apparatus II with paddles at 200 RPM, approximately 200 RPM, or approximately 250 RPM When used for delivery, it takes approximately 5, 8, 10, 12, or 15 minutes. , approximately 20 minutes, approximately 23 minutes, approximately 25 minutes, approximately 28 minutes, approximately 30 minutes, or approximately 35 minutes It is completely eluted in

[0036] In certain embodiments, the shell compositions disclosed herein can be used in a volume of 900 mL at 37° C. in 0.1N HCl and deionized water (optionally containing pepsin) at approximately 50 RPM About 250 RPM (e.g., about 50 RPM, about 75 RPM, about 100 RPM, about 150 RPM) Dissolving by USP Apparatus II with paddles at 200 RPM, approximately 200 RPM, or approximately 250 RPM When subjected to extraction, elution occurs in less than 15 minutes, less than 10 minutes, less than 9 minutes, less than 8 minutes, or less than 7 minutes. Start doing it.

[0037] In certain embodiments, the shell compositions disclosed herein can be used in a volume of 900 mL at 37° C. in 0.1N HCl and deionized water (optionally containing pepsin) at approximately 50 RPM About 250 RPM (e.g., about 50 RPM, about 75 RPM, about 100 RPM, about 150 RPM) Dissolving by USP Apparatus II with paddles at 200 RPM, approximately 200 RPM, or approximately 250 RPM When used for cooking, the time can range from about 1 minute, about 2 minutes, about 3 minutes, about 4 minutes, or about 5 minutes to about 7 minutes. The elution begins by about 8 minutes, about 9 minutes, about 10 minutes, or about 15 minutes.

[0038] In certain embodiments, the filling material encapsulated with the shell compositions disclosed herein A softgel composition (e.g., softgel capsule) containing the material may be stored at 37°C for 900 mL. In 0.1N HCl and deionized water (optionally containing pepsin), at about 50 RPM to about 250 RPM (e.g., about 50 RPM, about 75 RPM, about 100 RPM, about 150 RPM) Disintegration in a USP disintegration apparatus using paddles at approximately 200 RPM, or approximately 250 RPM When subjected to a begins to crack.

[0039] In certain embodiments, the filling material encapsulated with the shell compositions disclosed herein A softgel composition (e.g., softgel capsule) containing the material may be stored at 37°C for 900 mL. In 0.1N HCl and deionized water (optionally containing pepsin), at about 50 RPM to about 250 RPM (e.g., about 50 RPM, about 75 RPM, about 100 RPM, about 150 RPM) Disintegration in a USP disintegration apparatus using paddles at approximately 200 RPM, or approximately 250 RPM When subjected to the test, the time required for the test is approximately 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, or 7 minutes. , begin to burst by about 8 minutes, 9 minutes, 10 minutes, 15 minutes, or 20 minutes. .

[0040] In certain embodiments, the filling material encapsulated with the shell compositions disclosed herein A softgel composition (e.g., softgel capsule) containing the material may be stored at 37°C for 900 mL. In 0.1N HCl and deionized water (optionally containing pepsin), at about 50 RPM to about 250 RPM (e.g., about 50 RPM, about 75 RPM, about 100 RPM, about 150 RPM) Disintegration in a USP disintegration apparatus using paddles at approximately 200 RPM, or approximately 250 RPM When exposed to heat, the temperature is less than 45 minutes, less than 40 minutes, less than 35 minutes, less than 30 minutes, or less than 25 minutes. Dissolve completely.

[0041] In certain embodiments, the filling material encapsulated with the shell compositions disclosed herein A softgel composition (e.g., softgel capsule) containing the material may be stored at 37°C for 900 mL. In 0.1N HCl and deionized water (optionally containing pepsin), at about 50 RPM to about 250 RPM (e.g., about 50 RPM, about 75 RPM, about 100 RPM, about 150 RPM) Disintegration in a USP disintegration apparatus using paddles at approximately 200 RPM, or approximately 250 RPM When exposed to the temperature, the time is approximately 15 minutes, 18 minutes, 20 minutes, 22 minutes, or 25 minutes. The elution is complete by about 30 minutes, about 35 minutes, about 40 minutes, or about 45 minutes.

[0042] The dissolution and / or disintegration time of the shell composition is greater than the dissolution and / or disintegration time of the filler material. It should be understood that the time of disintegration and / or the amount of activity from the dosage form may be independent of the disintegration time. The release profile of a drug may vary depending on its shell and fill compositions. The dissolution and / or disintegration time of this shell composition is determined, at least in part, by the dosage form. The release profile of the active agent from the active agent may be suggested. According to an embodiment, the dosage form is administered as an immediate release dosage form (e.g., immediately using an immediate release fill material). The compositions may be formulated as controlled release dosage forms (by formulating a release shell composition). (e.g., by formulating an immediate release shell composition with a controlled release fill material) It may be formulated.

[0043] According to certain embodiments, the water-soluble polymer is, for example, polyvinyl alcohol (PVA ), pullulan gum, polylactic acid, polyvinyl alcohol-polyethylene glycol graft Copolymer (PVA-PEG copolymer), high molecular weight polyethylene glycol, povidone , surfactants (e.g., sodium lauryl sulfate), or combinations thereof. In one embodiment, the water-soluble polymer is PVA. In one embodiment, the water-soluble polymer is a PVA-PEG copolymer. High molecular weight polyethylene glycol is about 600 Da to about 2,000,0 The polyethylene glycol may be a polyethylene glycol having a number average molecular weight in the range of 0 to 100 Da, Any number average molecular weight (e.g., PEG600, PEG800, PEG1000, PEG 1500, PEG3350, PEG4000, PEG6000, PEG8000, etc.) In certain embodiments, the water-soluble polymer may be polyethylene glycol. In the shell composition, for example, about 0.5 wt.% to about 10 wt.%, about 0.5 wt. .% ~ approx. 12wt.%, approx. 1wt.% ~ approx. 15wt.%, approx. 1wt.% ~ approx. 20wt.% , about 2wt.%~about 22wt.%, about 2wt.%~about 7wt.%, about 0.5wt.%~about 8wt.%, about 3wt.% to about 9wt.%, about 2.5wt.% to about 30wt.%, about 10 wt.% ~ approx. 50wt.%, approx. 20wt.% ~ approx. 40wt.%, approx. 15wt.% ~ approx. 30 wt.%, approx. 15wt.%, approx. 18wt.%, approx. 20wt.%, approx. 22wt.%, approx. 25 % by weight, about 28% by weight, about 30% by weight, or any subrange therein Amounts are single concentration values ​​and all wt.% are based on the total weight of the shell composition .

[0044] According to embodiments, the non-animal gelling agent may be, for example, carrageenan, starch, alpha Modified starch, xanthan gum, agar, pectin, alginate, sugar, sugar-derived alcohol, Monosaccharides, disaccharides, oligosaccharides, cellulose derivatives, cellulose-based polymers, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, Carboxymethylcellulose, microcrystalline cellulose, attapulgite, bentonite, de Kistrin, alginate, kaolin, lecithin, magnesium aluminum silicate, calcium Carbomer, Carbopol (trademark), Silicon dioxide, Curdlan, cerelen, albumin (e.g., egg- or lacto-derived), soybean Protein, chitosan, guar gum, tamarind seed polysaccharide, glucomannan, chitin, The surfactant may comprise a pluran, a cyclodextrin, or a combination thereof.

[0045] The carrageenan may be iota carrageenan, kappa carrageenan, or lambda carrageenan. The compound may be at least one of the following:

[0046] The starch may be modified or native starch, sweet potato starch, potato starch, Starch, corn starch, tapioca starch, pea starch, hydroxy Dipropylated starch, hydroxyalkylated starch, acid-treated starch, dextrin , high amylose unmodified corn starch, modified waxy corn starch, non-granular starch, modified high amylose corn starch, pregelatinized rice flour, and their derivatives As used herein and in the claims, "modified starch" refers to a starch or a mixture thereof. The term includes starches such as hydroxypropylated starch, acid diluted starch, etc. Generally, modified starches are products prepared by chemical treatment of starch, e.g. Acid-treated starch, enzyme-treated starch, oxidized starch, cross-linked starch, and other starches This modified starch is derivatized so that the side chains are modified with hydrophilic or hydrophobic groups. It is preferable to form a more complex structure with strong interactions between the side chains by .

[0047] In certain embodiments, the non-animal gelling agent is present in the shell composition, e.g., at about 2 wt. t.% ~ approx. 20wt.%, approx. 2wt.% ~ approx. 15wt.%, approx. 2wt.% ~ approx. 40wt. %, about 10wt.%~about 80wt.%, about 15wt.%~about 75wt.%, about 20wt. % ~ approx. 70wt.%, approx. 25wt.% ~ approx. 60wt.%, approx. 25wt.% ~ approx. 45wt. %, about 20wt.%~about 35wt.%, about 30wt.%~about 40wt.%, about 32wt. %, about 35 wt.%, about 38 wt.%, or any subrange or single range therein. All wt.% are based on the total weight of the shell composition. In embodiments, the non-animal gelling agent includes carrageenan, starch (or modified starch). In one embodiment, the softgel shell composition does not contain starch (or substantially free of starch (or modified starch) or free of starch (or modified starch) stomach.

[0048] In certain embodiments, water-soluble polymers (e.g., PVA, PVA-PEG copolymers) non-animal gelling agents (e.g., carrageenan, dextran, pullulan, or combinations thereof) starch, or a combination thereof) is about 20:1 to about 1:20, about 15: 1 to about 1:15, about 10:1 to about 1:10, about 8:1 to about 1:8, about 5:1 to about 1:5, It may be in the range of about 3:1 to about 1:3, or about 2:1 to about 1:2, or about 1:1. Although not intended to be limiting, the invention also includes non-animal gelling agents for water-soluble polymers. The weight ratios of these components contribute to the dissolution time of the softgel shell compositions described herein. It is believed that...

[0049] According to an embodiment, the buffering agent is sodium phosphate dibasic, sodium phosphate monobasic, carbonated water Sodium citrate, sodium phosphate, calcium phosphate, dibasic phosphate calcium phosphate, tricalcium phosphate, monopotassium phosphate, and dipotassium phosphate In an embodiment, the buffering agent comprises dibasic sodium phosphate. In an embodiment, the buffering agent is present in the shell composition in an amount of from about 0.01 wt.% to about 5 wt.%. .%, about 0.05wt.%~about 4wt.%, about 0.1wt.%~about 3wt.%, about 0.5 wt.% to about 3 wt.%, about 1.0 wt.%, or any subrange therein Amounts are single concentration values ​​and all wt.% are based on the total weight of the shell composition .

[0050] According to various embodiments, the plasticizer may be, for example, glycerin, sorbitol, A solution of sorbitan, triacetin, polysorbate, propylene glycol, and lauric acid. sodium sulphate (SLS), sugar alcohols (e.g., maltitol), or their In certain embodiments, the plasticizer is glycerin. In one embodiment, the plasticizer is sorbitol. In one embodiment, the plasticizer is SLS. In embodiments, the plasticizer is present in the shell composition in an amount of from about 0.5 wt.% to about 40.0 wt.%. .%, 10wt.% ~ approx. 30.0wt.%, approx. 12wt.% ~ approx. 28wt.%, approx. 15w t.% ~ approx. 30wt.%, approx. 18wt.% ~ approx. 23wt.%, approx. 18wt.%, approx. 20w t.%, about 22 wt.%, about 25 wt.%, about 28 wt.%, about 30 wt.%, or Any subrange or single concentration value of the amount of Based on total weight of formulation.

[0051] In certain embodiments, the softgel capsule shell composition contains water. In the shell composition, about 30 wt.% to about 60 wt.%, about 35 wt.% to about 55 wt.% , about 40wt.% to about 50wt.%, about 42wt.%, about 43wt.%, about 44wt.% , about 45wt.%, about 45.5wt.%, about 46wt.%, about 47wt.%, about 48wt %, or any subrange or single concentration value therein, All wt.% are based on the total weight of the shell composition. The weight ratio of water to non-animal gelling agent in the shell composition is about 1:5 to about 5:1 , about 1:4 to about 4:1, about 1:3 to about 3:1, about 1:1, about 2:1, about 3:1, about 4:1 , or about 5:1.

[0052] In certain embodiments, the softgel shell compositions described herein are As measured by a texture analyzer according to the details explained in the example, it is approximately 5 The film strength is greater than about 5.0 kg, greater than about 5.2 kg, or greater than about 5.4 kg. In embodiments, the softgel shell compositions described herein contain about 3.5 kg, From approximately 4.0 kg, approximately 4.5 kg, approximately 5.0 kg, or approximately 5.5 kg , approx. 6.0kg, approx. 6.5kg, approx. 7.0kg, approx. 7.5kg, approx. 8.0kg, approx. 8.5 kg, approx. 9.0kg, approx. 9.5kg, approx. 10.0kg, approx. 10.5kg, approx. 11.0kg , about 11.5 kg, or about 12.0 kg, or any of the ranges therein In certain embodiments, the film strength may be a single value or a subrange. The softgel shell composition described in kg to approximately 12.0 kg, approximately 5.2 kg to approximately 10.0 kg, or approximately 5.0 kg to approximately 7.0 It has a film strength in the range of kg.

[0053] In certain embodiments, the softgel shell compositions described herein are As measured by a texture analyzer according to the details explained in the example, it is approximately 7 The elasticity may be greater than about 0.7 mm, greater than about 8.0 mm, or greater than about 8.2 mm. In the softgel shell compositions described herein, the softgel shell compositions are m, approximately 7.0 mm, approximately 7.5 mm, approximately 8.0 mm, or approximately 8.5 mm, Approx. 9.0mm, Approx. 9.5mm, Approx. 10.0mm, Approx. 10.5mm, Approx. 11.0mm, Approx. 1 1.5 mm, or approximately 12.0 mm, or any single In certain embodiments, the methods described herein have flexibility in the values ​​or subranges. The softgel shell composition may be from about 6.0 mm to about 12.0 mm, from about 7.0 mm to about 10.0 mm. Elasticity of .0mm, approximately 8.0mm to approximately 12.0mm, or approximately 8.0mm to approximately 10.0mm It has sexuality.

[0054] In certain embodiments, the softgel shell compositions described herein are It should be elastic enough to allow cell formation, but not so elastic that it can be easily encapsulated (e.g., by rotating the It is also strong enough to be handled in a die and has a melting point below the melting point of the softgel shell composition. and providing good sealing properties at temperatures ranging from 100°C to 120°C, all of which are consistent with the soft gel shell composition and and does not impair the dissolution or disintegration profile of the capsule.

[0055] The softgel capsule formulations disclosed herein may further comprise a fill material. The filler material is rapeseed oil, medium chain triglyceride oil, polyethylene glycol, and It may contain at least one of the lipophilic and / or hydrophilic combinations thereof. and / or alcohol fill material may be used in the softgel capsule filling described herein. It may be packaged with a filler material.

[0056] Active Agent Any pharmaceutically active ingredient may be used for the purposes of the present invention, including water-soluble Suitable pharmaceutical active ingredients include, but are not limited to, those that are soluble in water and those that are poorly soluble in water. Not specified, but includes analgesics and anti-inflammatory agents, antacids, anthelmintics, antiarrhythmics, antibacterials, and anticoagulants , antidepressants, antidiabetics, antidiarrheals, antiepileptics, antifungals, antigout agents, antihypertensives, antimalarials anti-inflammatory drugs, anti-migraine drugs, anti-muscarinic agents, anti-tumor and immunosuppressants, anti-protozoal agents, anti-rheumatic drugs Eumatic drugs, antithyroid drugs, antiviral drugs, anxiolytics, sedatives, hypnotics and neuroleptics, beta -blockers, cardiac inotropes, corticosteroids, antitussives, cytotoxic agents, decongestants, diuretics, enzymes Anti-Parkinson's agents, gastrointestinal agents, histamine receptor antagonists, lipid regulators, local anesthetics, Muscle-relieving drugs, nitrates and antianginal drugs, nutritional supplements, opioid analgesics, oral vaccines, proteins substances, peptides and recombinant drugs, sex hormones and contraceptives, spermicides, stimulants, and Combinations thereof are included.

[0057] In some embodiments, the active pharmaceutical ingredient includes, but is not limited to, dabigatran. Ran, dronedarone, ticagrelor, iloperidone, ivacaftor, midostaurin, a Simadoline, beclomethasone, apremilast, sapacitabine, linsitinib, abirate vitamin D analogs (e.g., calcifediol, calcitriol, parical cetyl, doxercalciferol), COX-2 inhibitors (e.g., celecoxib, Ludecoxib, rofecoxib), tacrolimus, testosterone, lubiprostone, drugs The compound may be selected from the group consisting of pharmaceutically acceptable salts thereof, and combinations thereof.

[0058] In some embodiments, the lipid in the dosage form includes, but is not limited to, amphotericin, methylparaben ... Indian oil, argan oil, avocado oil, borage seed oil, canola oil, cashew oil, castor oil Oil, hydrogenated castor oil, cocoa butter, palm oil, rapeseed oil, corn oil, cottonseed oil, grape Seed oil, hazelnut oil, hemp oil, hydroxylated lecithin, lecithin, flaxseed oil, macadamia Oil, mango butter, manila oil, mongongo nut oil, olive oil, palm kernel oil, palm Oil, peanut oil, pecan oil, perilla oil, pine nut oil, pistachio oil, poppy seed oil, kabochi Seed oil, rice bran oil, safflower oil, sesame oil, shea butter, soybean oil, sunflower oil, hydrogenated vegetable oil The oils and fats may be selected from the group consisting of peanut oil, walnut oil, and watermelon seed oil. including but not limited to fish oil (omega-3), krill oil, animal or vegetable fats, such as For example, their hardened forms, free fatty acids, as well as C8-, C10-, C12-, C14-, Mono-, di-, and tri- with C16-, C18-, C20-, and C22- fatty acids -glycerides, and combinations thereof.

[0059] According to certain embodiments, the active agent includes, but is not limited to, a statin (e.g., Lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin, and pitavastatin), fibrates (e.g., clofibrate, Ciprofibrate, bezafibrate, fenofibrate, and gemfibrozil ), niacin, bile acid sequestrants, ezetimibe, lomitapide, phytosterols, and Pharmaceutically acceptable salts, hydrates, solvates, and prodrugs thereof, any of the foregoing Lipid-lowering agents, including mixtures thereof, may be included.

[0060] Suitable nutraceutical active agents include, but are not limited to, 5-hydroxytryptophan. Vitamin D3, Acetyl L-Carnitine, Alpha Lipoic Acid, Alpha Ketoglutarate, Bee Products, Salt Acid Betaine, Bovine Cartilage, Caffeine, Cetyl Myristoliate, Charcoal, Chitosan, Choline , chondroitin sulfate, coenzyme Q10, collagen, colostrum, creatine, cyanoco Baramin (Vitamin 812), Dimethylaminoethanol, Fumaric Acid, Germanium Oxide Glucosamine, Glandular Products, Glucosamine HCl, Glucosamine Sulfate, Hydroxymethylbutyrate, Immunoglobulin Lactic acid, L-carnitine, liver product, malic acid, maltose anhydrous, mannose (d-mannose), methylsulfonylmethane, phytosterols, picolinic acid, pyridoxine hydrochloride Vinyl acetate, red yeast extract, S-adenosylmethionine, selenium yeast, shark cartilage, theobromine May contain romine, vanadyl sulfate, and yeast.

[0061] Suitable nutritional supplement active agents include vitamins, minerals, fiber, fatty acids, amino acids, and herbs. supplements, or a combination thereof.

[0062] Suitable vitamin active agents include, but are not limited to, the following: ascorbic acid (vitamin A); Vitamin C), B vitamins, biotin, fat-soluble vitamins, folic acid, hydroxycitric acid, inosinate Sitol, mineral ascorbate, mixed tocopherols, niacin (vitamin B3) , orotic acid, para-aminobenzoic acid, pantothenate, pantothenic acid (vitamin B5) , pyridoxine hydrochloride (vitamin B6), riboflavin (vitamin B2), synthetic vitamins, Thiamine (vitamin B1), tocotrienol, vitamin A, vitamin D, vitamin E, May contain vitamin F, vitamin K, vitamin oils, and oil-soluble vitamins.

[0063] Suitable herbal supplement active agents include, but are not limited to, the following: arnica, Bilberry, black cohosh, cat's claw, chamomile, echinacea, evening primrose oil, Fenugreek, flaxseed, feverfew, garlic, ginger root, ginkgo biloba, Ginseng, goldenrod, hawthorn, kava, licorice, milk thistle, and osmanthus Ko, Indian jabok, senna, soybean, St. John's wort, saw palmetto, turmeric, May contain valerian.

[0064] Mineral active agents include, but are not limited to, the following: boron, calcium, chelate Minerals, chloride, chromium, coated minerals, cobalt, copper, dolomite Iron, iodine, magnesium, manganese, mineral premixes , mineral products, molybdenum, phosphorus, potassium, selenium, sodium, vanadium, phosphorus May contain niacin, pyruvate, zinc, and other minerals.

[0065] Examples of other possible active agents include, but are not limited to, antihistamines (e.g., , ranitidine, dimenhydrinate, diphenhydramine, chlorpheniramine, and d-chlorpheniramine maleate), nonsteroidal anti-inflammatory drugs (e.g., aspirin, Celecoxib, Cox-2 inhibitors, diclofenac, benoxaprofen, flurbipro Fen, fenoprofen, flubufen, indoprofen, pyroprofen, carp Profen, Oxaprozin, Pramoprofen, Muroprofen, Trioxaprofen , suprofen, aminoprofen, fluprofen, buclic acid, indomethacin, Sulindac, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, Clidanac, oxypinac, meclofenamic acid, flufenamic acid, niflumic acid, tolfenamic acid Namic acid, diflurisal, flufenisal, piroxicam, sudoxicam , isoxicam, aceclofenac, aloxiprine, azapropazone, benorilate , Bronfenac, Carprofen, Choline Magnesium Salicylate, Diflunisal, E Todolac, etoricoxib, physlamine, fenbufen, fenoprofen, fluconazole Ibuprofen, indomethacin, ketoprofen, ketorolac, Lunoxicam, loxoprofen, meloxicam, mefenamic acid, metamizole, salicylic acid Methyl salicylate, magnesium salicylate, nabumetone, naproxen, nimesulide, oxytocin Phenbutazone, parecoxib, phenylbutazone, salicylate, sulindac, Sulfinpyrazone, tenoxicam, tiaprofenic acid, tolmetin, pharmaceutically acceptable and their salts, and mixtures thereof, acetaminophen, antiemetics (e.g., methotrexate, antiepileptic drugs (e.g., phenytoin, mepromethazine, methylnaltrexone), nitrazepam), vasodilators (e.g., nifedipine, papaverine, zilch Azem, and nicardipine), cough suppressants and expectorants (e.g., codeine phosphate), antiasthmatics Breath medications (e.g., theophylline), antacids, antispasmodics (e.g., atropine, scopolamine) , antidiabetic drugs (e.g., insulin), diuretics (e.g., ethacrynic acid, bendroflume thiazides), antihypertensives (e.g., propranolol, clonidine), antihypertensives (e.g., bronchodilators (e.g., albuterol), steroids Medications (e.g., hydrocortisone, triamcinolone, prednisone), antibiotics (e.g., Tetracycline), anti-hemorrhoid, hypnotic, psychotropic, antidiarrheal, mucolytic, sedative, decongestant Expectorants (e.g., pseudoephedrine), laxatives, vitamins, stimulants (e.g., phenylpropanol), In addition to cannabinoids, pharmaceutically acceptable The term "compounds" includes salts, hydrates, solvates, and prodrugs thereof.

[0066] The active agent is a benzodiazepine, a barbiturate, a stimulant, or a mixture thereof. The term "benzodiazepines" refers to benzodiazepines and central nervous system This refers to drugs that are derivatives of benzodiazepines that can suppress the neurotransmitter system. , including but not limited to alprazolam, bromazepam, chlordiazepoxide, chlor Razepam, diazepam, estazolam, flurazepam, halazepam, ketazolam, lorazepam Pam, nitrazepam, oxazepam, prazepam, quazepam, temazepam, triazola methylphenidate, as well as pharmaceutically acceptable salts, hydrates, solvates thereof, The active agent may be a benzodiazepine, a prodrug, or a mixture thereof. Zepine antagonists include, but are not limited to, pharmaceutically acceptable azepine antagonists in addition to flumazenil. Salts, hydrates, solvates, and mixtures thereof are included.

[0067] The term "barbiturates" refers to barbituric acid (2,4,6-trioxohexyl Barbiturates are sedative-hypnotic drugs derived from benzodiazepines (benzothiazolinone, benzodiazepines, benzothiazolinone ... However, amobarbital, aprobarbital, butabarbital, and butalbital , methohexital, mephobarbital, metharbital, pentobarbital, phen Novarbital, secobarbital, and pharmaceutically acceptable salts and hydrates thereof, This includes solvates, prodrugs, and mixtures thereof. Barbiturate antagonists include, but are not limited to, those pharmaceutically active in addition to amphetamines. Acceptable salts, hydrates, solvates, and mixtures thereof are included.

[0068] The term "stimulant" includes, but is not limited to, dextroamphetamine resin complexes. Body like amphetamine, dextroamphetamine, methamphetamine, methylphenidamine Nidate, as well as pharmaceutically acceptable salts, hydrates, solvates, and the like thereof. Stimulant antagonists that may be used as active agents include, but are not limited to, benzodiazepines ... benzodiazepines, as well as pharmaceutically acceptable salts, hydrates, solvates, and the like thereof. It includes mixtures of these.

[0069] The softgel capsule formulations described in this disclosure contain various active agents and their pharmaceutically acceptable salts. Pharmaceutically acceptable salts include, but are not limited to, hydrochloride salts. Inorganic acid salts such as hydrobromides, sulfates, phosphates, etc., formates, acetates, trifluorides, Organic acid salts such as acetates, maleates, tartrates, etc., methanesulfonates, benzenesulfonates, etc. sulfonates such as toluenesulfonate, p-toluenesulfonate, etc., arginate , amino acid salts such as aspartate, glutamate, etc., sodium salts, potassium salts, metal salts such as cesium salts, alkali salts such as calcium salts, magnesium salts, etc. alkali earth metals, triethylamine salts, pyridine salts, picoline salts, ethanolamine salts, tri Ethanolamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine Examples of suitable salts include organic amine salts such as amine salts.

[0070] Method for preparing a softgel capsule formulation The softgel shell compositions and softgel capsule formulations as disclosed herein A method of preparation is disclosed herein, which method comprises adding a non-animal a water-soluble gelling agent, a water-soluble polymer, and optionally at least one of a buffer, a plasticizer, or water. The method includes blending at least one of the blends to form a molten mass. In embodiments, the molten mass is a homogeneous molten mass. The method may further include extruding the molten mass to form a ribbon. Additionally, the method uses a rotary die encapsulation device to cast the ribbon onto a drum. and forming a soft capsule shell. In an embodiment, the ribbon comprises: For example, about 0.001 inches to about 0.100 inches (about 0.0254 mm to about 2.54 m) m), approximately 0.001 inches to approximately 0.070 inches (approximately 0.0254 mm to approximately 1.78 mm ), approximately 0.001 inches to approximately 0.050 inches (approximately 0.0254 mm to approximately 1.27 mm) , approximately 0.005 inches to approximately 0.030 inches (approximately 0.127 mm to approximately 0.762 mm), Approximately 0.010 inches to approximately 0.025 inches (approximately 0.254 mm to approximately 0.635 mm), approximately 0.015 inches to approximately 0.021 inches (approximately 0.381 mm to approximately 0.533 mm), approximately 0 .017 inches (approx. 0.432 mm), approx. 0.018 inches (approx. 0.457 mm), approx. 0 .019 inches (approx. 0.483 mm), approx. 0.020 inches (approx. 0.508 mm), approx. 0 .021 inches (approximately 0.533 mm) or approximately 0.022 inches (approximately 0.559 mm) In certain embodiments, a network formed from the formulation may have a thickness of This netting can then be melted and reused to form ribbons.

[0071] In one embodiment, the method includes forming a plasticizer solution when both a plasticizer and water are present. The method may further include mixing a plasticizer with water to form a synthetic polymer. -, a non-animal (natural) gelling agent, and a buffering agent (if present) are mixed with the plasticizer solution. In the same or alternative embodiment, the combination may further comprise: mixing a plasticizer with a non-animal gelling agent to form a solution; forming a plasticizer solution; mixing the solution with water and plasticizing the water-soluble polymer and buffer to form a The method may further comprise mixing the mixture with a gelling agent solution (including a non-animal gelling agent therein). In this case, the water-soluble polymer, the non-animal gelling agent, the buffer, the plasticizer, and the water are each mixed at low shear. In embodiments, the blending may be performed for about 1 minute to about 3 minutes. Time, about 5 minutes to about 2.5 hours, about 15 minutes to about 2.0 hours, about 20 minutes to about 1.5 hours, about 3 The blending time can be from about 45°C to about 90°C for 1.0 minutes to 1.0 hour, or from about 5 minutes to about 30 minutes. °C, about 50°C to about 85°C, about 55°C to about 80°C, about 60°C to about 70°C, about 55°C, about 60 The blending may be carried out at a temperature of about 95°C to about 125°C, or about 100°C. ~120℃, ~105℃~115℃, ~95℃, ~96℃, ~97℃, ~98℃, It may further comprise increasing the temperature to 99°C, or about 100°C.

[0072] According to certain embodiments, the method may further comprise transferring the formulation to a receiving vessel. The mixture or material in the receiving vessel is transferred to a heated vessel in which the material is heated. In certain embodiments, the heated vessel may be heated to a temperature of about 80°C to It can be heated to a temperature of about 115°C, about 85°C to about 100°C, or about 88°C to about 95°C. According to certain embodiments, the method may include injecting a colorant into the formulation. stomach.

[0073] The method may further comprise transferring the formulation to an encapsulation device. In one embodiment, the method comprises: and encapsulating the fill material within a softgel capsule fill material formed from any of the above compounds. The method may include drying a plurality of softgel capsule dosage forms in a tumble dryer. Certain embodiments may further include packaging a plurality of softgel capsule dosage forms. The method may further include dressing the device.

[0074] treatment The active agent contained in the fill material of the softgel capsules described herein Treating, preventing, or minimizing a treatable condition in a subject in need thereof A method for preventing or ameliorating the disease is disclosed herein. Administer any of the listed softgel capsules to a subject in need thereof. and wherein administration of the softgel capsule treats or prevents said condition. , minimized, ameliorated, or alleviated.

[0075] The terms "treatment of" and "treating" are used to describe a condition with the goal of reducing the severity of the condition. This includes administering an active agent.

[0076] The terms "prevention of" and "preventing" refer to the prevention of the onset of a condition by prophylactic administration of an active agent. This includes avoiding

[0077] The term "condition" or "conditions" refers to an effective amount of the or may be treated by administration of any of the active or cosmetic agents described in the literature; It may refer to a condition that can be prevented, minimized, or ameliorated. In certain embodiments, the term "condition" or "conditions" The term may refer to pain.

[0078] In certain embodiments, the softgel capsules described herein (e.g., non- an animal-derived gelling agent, a water-soluble polymer, and at least one of a buffer, a plasticizer, and water The polymers (including any one of the polymers) may be prepared by mixing the polymers with the components listed hereinabove (such as water-soluble polymers). Faster T than softgel capsules that do not contain one of the max contribute to.

[0079] T max is the plasma concentration of the active drug at C max It refers to the time it takes to reach

[0080] C max refers to the peak plasma concentration of the active drug.

[0081] As used herein, the term "effective amount" refers to an amount that produces a desired therapeutic or cosmetic result. It refers to the amount and / or proportion of active pharmaceutical or cosmetic agent required to produce a desired effect.

[0082] The term "subject" refers to a person who is a candidate for treatment with any of the active agents described herein. Refers to a human or animal that exhibits the onset of a condition (clinical or otherwise) that indicates a need. [Example]

[0083] Specific embodiments of the present disclosure will now be demonstrated by reference to the following examples. It will be understood that these examples are disclosed only for the purpose of illustrating the present disclosure. and should in no way be construed as limiting the scope of this disclosure. It's not that.

[0084] [Example 1] A non-animal gelling agent capsule shell composition containing no water-soluble polymer (control) and a water-soluble Softgel capsules made in a non-animal gelling agent capsule shell composition containing an animal-derived gelling agent and an animal-derived polymer The dissolution was compared in 900 mL of 0.1 N HCl and deionized water at 37°C for 7 min. Tested using USP Apparatus II with paddles at 5 RPM. Test shell compositions are 1000 psi diameter. 1.0 inch (25.4 mm) and 0.7 mm and 1.4 mm thick samples. do.

[0085] [Table 1-1]

[0086] [Table 1-2]

[0087] As can be seen in Table 1, the control non-animal gelling agent capsule system did not contain a water-soluble polymer. The well compositions had dissolution times in water of 63.25 minutes and 71.05 minutes. In this study, water-soluble polymers (PVA alone, PVA with SLS, or PVA-PEG copolymer) were used. All non-animal gelling agent capsule shell compositions containing any of the polymers are Much better in water (less than 20 minutes) and in 0.1N HCl (less than 25 minutes). It eluted quickly.

[0088] Interestingly, the non-animal gelling agent capsule shell composition containing PVA with SLS In the case of SLS, faster dissolution was observed than in the case of any of the other water-soluble polymers. The shell composition containing PVA without PVA was prepared by using a PVA-PEG copolymer as the water-soluble polymer. The dissolution rate was comparable to that of the shell composition containing .

[0089] Although not intended to be limiting, the present invention relates to specific water-soluble polymers of carrageenan. Similar to the weight ratio, the type of water-soluble polymer may affect the dissolution time of the shell composition. It is thought that there is a gender.

[0090] [Example 2] As shown in Table 2 below, the solubility of various softgel shell compositions, whether natural or synthetic, is significantly improved. The evaluation was carried out by blending synthetic water-soluble polymers.

[0091] [Table 2]

[0092] A softgel shell composition was prepared for each of the above formulations (F-1 to F-6). Formulation F-1 Shell compositions F-1 to F-4 were cast into films. Shell compositions F-1 to F-4 were dried and then The water content was 6 wt.% to 15 wt.% based on the total weight of the shell composition. The film strength and elasticity of the dried shell composition was evaluated using a film analyzer. Table 3 shows the strength and hardness of shell compositions prepared using various water-soluble polymers. This data is based on the total weight of the softgel shell composition. It is produced using a dry shell composition containing a moisture content of 0.05% to 15 wt.%.

[0093] The texture analyzer test conditions for measuring strength and elasticity are as follows: The soft gel films having compositions F-1 to F-4 were placed on the platform. A quarter-inch (6.35 mm) ball probe was placed on the film. The force measured was 2 mm / sec toward the softgel film until the force was passed through. The measured distance was the strength of the film. The measured distance was the elasticity of the film. was carried out under the conditions.

[0094] [Table 3]

[0095] As can be seen in Table 3, the control non-animal gelling agent capsule system containing no water-soluble polymer The shell composition had a strength of 4.9 kg and a resilience of 7.5 mm. Water-soluble polymers (PVA alone, pullulan, or PVA-PEG copolymer) All non-animal gelling agent capsule shell compositions containing any of the above have a strength greater than 5 kg. It was stronger and more resilient with a resilience of over 8 mm.

[0096] [Example 3] Softgel Shell Composition - Dissolution Data The soft gel shell compositions prepared with different concentrations and types of water-soluble polymer were The samples were cut into 1 inch x 1 inch squares and their solubility was checked by 0.1N dilution with deionized water at 37°C. in HCl at 0.1 N using USP Apparatus II with a paddle rotation speed of 75 RPM The shell compositions were evaluated in HCl. Table 4 shows the shell compositions prepared using various water-soluble polymers. The solubility data (also called dissolution data) for

[0097] The types of carrageenan, plasticizers, and buffers used in the samples in Table 4 below. The concentrations were the same as those listed in Table 2 for formulations F-2 through F-6.

[0098] [Table 4]

[0099] Although not intended to be limiting, the present invention relates to specific water-soluble polymers of carrageenan. Similar to the weight ratio, the type of water-soluble polymer may affect the dissolution time of the shell composition. It is thought that there is a gender.

[0100] [Example 4] Softgel Capsule Formulations - Dissolution / Disintegration Data Placebo softgel capsules were prepared using polyvinyl alcohol and pullulan. The softgel capsule contained 900 mg of soybean oil as the fill material. The softgel shell composition encapsulating the filler was used in Table 2 for formulations F-2 to F-6. The formulation contained the specified types and concentrations of carrageenan, plasticizer, and buffering agent. The type and concentration of water-soluble polymers in each softgel filling material are listed in Table 5. After drying the capsules, they were subjected to dissolution testing and found to be: The burst time / dissolution rate of the capsules was evaluated.

[0101] Elution method: Equipment: USP Equipment II Temperature: 37℃ Medium: 0.1N HCl Paddle rotation speed: 50 and 75 RPM

[0102] [Table 5]

[0103] As can be seen from Table 5, the shell composition containing the water-soluble polymer (PVA or pullulan) The softgel capsules used were faster in 0.1N HCl at 75 RPM and 37°C. The shell composition containing pullulan exhibited a shorter dissolution time than the control, The dissolution time was faster than that of the shell composition containing PVA. The shell composition is 0.1N HCl at 50 RPM and 37°C. Similar elution times were maintained in 0.1 N HCl containing pepsin.

[0104] The control samples were non-gelatin soft gel capsules containing no pullulan and 2 wt. % pullulan using a USP disintegration apparatus. The results are shown in Table 6. The capsules burst much faster than the softgels without pullulan. The addition resulted in faster disintegration.

[0105] [Table 6]

[0106] [Example 5] Comparative dissolution of ibuprofen softgel capsules Contains 200 mg of ibuprofen manufactured using a standard non-gelatin shell composition and 2 wt.% pullulan. Comparative dissolution tests were performed using the non-gelatin shell compositions described in the examples. A soft gel capsule (CS100A) containing 2 wt.% pullulan was used. The softgel composition for the non-gelatin softgel capsules according to the present invention is as shown in Table 7 below. The results of this test are summarized in Figure 1. This dissolution test was performed using 0.1N ethanol at 37°C. It was carried out in USP Apparatus II using a paddle rotation speed of 75 RPM in HCl.

[0107] [Table 7]

[0108] This result is consistent with the results of the non-gelatin ebullient described in one embodiment, which contains 2 wt.% pullulan. The Lofen 200mg softgel capsules burst in 24 minutes, a standard non-gelatin eve It burst in 18 minutes, faster than the 200mg softgel capsule of Profen. The F2 factor was calculated to be 40, indicating that the two elution profiles were different. Pullulan softgel capsules were compared with the control non-gelatin ibuprofen 20 0 mg softgel capsules, which has a faster drug release rate than the 0 mg softgel capsules, resulting in a faster onset of drug efficacy and and shorter T max may be useful in achieving this.

[0109] The term "similarity factor (f2)" indicates the similarity of the release profiles of the two dosage forms. If the f2 value is not less than about 50, the release profiles of the two dosage forms are are relative, similar, or bioequivalent (to a solid oral dosage form) FDA Guidance issued in December 2017 regarding bioequivalence studies to Industry).

[0110] The foregoing description provides a good understanding of some embodiments of the present invention, and is provided with reference to specific systems. Although numerous specific details are set forth, such as examples of systems, ingredients, methods, etc., the present invention It is understood that at least some embodiments of the present invention may be practiced without these specific details. In other instances, well-known ingredients or methods may be used in the present invention. To avoid unnecessarily obscuring the invention, the invention has not been described in detail. The specific details set forth are exemplary. Particular embodiments may incorporate these exemplary details. The details may be varied and still be considered within the scope of the present invention.

[0111] Although the method operations herein are described in a particular order, the order of operations in each method It is important to note that certain operations may be performed in reverse order, or that certain operations may be performed in at least Some parts may be modified so that they may be performed in parallel with other operations. In this configuration, instructions for separate operations or sub-operations are performed intermittently and / or alternately. That's fine.

[0112] The above description is intended to be illustrative and not restrictive. It should be understood that many other embodiments are possible in light of the above description. The scope of the present invention will be apparent to those skilled in the art upon reading the appended claims. Reference should be made to the claims and all equivalents to which such claims are entitled. This should be determined in conjunction with the scope.

Claims

1. A shell composition comprising a non-animal derived gelling agent and a water-soluble polymer, the shell composition having a gelling ability of 90°C at 37°C. USP apparatus with paddles at 75 RPM in 0 mL of 0.1 N HCl and deionized water A shell composition that completely dissolves in less than 30 minutes when subjected to dissolution by II; and a filler material encapsulated within said shell composition; 1. A softgel composition comprising:

2. The non-animal derived gelling agent is selected from the group consisting of carrageenan, starch, pregelatinized starch, xanthan gum, and the like. Gum, agar, pectin, alginate, sugar, high molecular weight polyethylene glycol, sugar-derived Alcohols, cellulose derivatives, cellulose-based polymers, hydroxyethyl cellulose, Hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl Cellulose, microcrystalline cellulose, attapulgite, bentonite, dextrin, aloe Sodium glutamate, kaolin, lecithin, magnesium aluminum silicate, carbomer, Bopol, silicon dioxide, curdlan, furcellaran, albumin, soy protein, 10. The softgel composition of claim 1, comprising a hydroxybenzoate, ...

3. 3. The softgel composition of claim 1, wherein the shell composition further comprises a plasticizer. 。

4. The soft shell composition of claim 1 , wherein the shell composition further comprises a buffer. Togel composition.

5. The water-soluble polymer is polyvinyl alcohol, pullulan gum, polylactic acid, polyvinyl Alcohol-polyethylene glycol graft copolymer, high molecular weight polyethylene glycol 5. The composition of claim 1, further comprising a surfactant, povidone, a surfactant, or a combination thereof.

10. The softgel composition of claim 1.

6. 6. The softgel composition of claim 5, wherein the surfactant is sodium lauryl sulfate. 。

7. The shell composition may be heated for less than 25 minutes, less than 20 minutes, less than 15 minutes, less than 10 minutes, or less than 5 minutes.

7. The softgel composition of claim 1, wherein the softgel dissolves in less than 1000 mg of water.

8. 8. Any of claims 1 to 7, wherein the non-animal derived gelling agents include carrageenan and starch.

10. The softgel composition of claim 1 .

9. The weight ratio of carrageenan to starch in the shell composition is from about 1:1 to about 1 :10, about 1:1 to about 1:8, about 1:1 to about 1:5, or about 1:2.5 to about 1:4.5 9. The softgel composition of claim 1, wherein

10. The carrageenan may be iota carrageenan, kappa carrageenan, or lambda carrageenan.

10. The softgel composition of claim 9, comprising:

11. The starches include native starch, modified starch, potato starch, corn starch, Starch, tapioca starch, pea starch, hydroxypropylated starch, Hydroxyalkylated starch, acid-treated starch, dextrin, and combinations thereof 11. The softgel composition of claim 9 or 10, comprising:

12. The non-animal gelling agent comprises about 100 parts by weight of the softgel capsule shell composition.

12. The softener of claim 1, in an amount of 2 wt. % to about 40 wt. %. Togel composition.

13. Less than 10 wt. %, less than 5 wt. %, based on the total weight of said softgel capsule shell composition. % or less than 1 wt. % animal-derived gelling agent.

10. The softgel composition of claim 1.

14. 14. Any one of claims 1 to 13, wherein the shell composition does not contain an animal-derived gelling agent. Item 1. The softgel composition according to item 1.

15. The plasticizer may be glycerin, sorbitol, a solution of sorbitol and sorbitan, trimethylsilyl methylcellulose, or the like.

4. The softener of claim 3, comprising acetone, sodium lauryl sulfate, or a combination thereof. Togel composition.

16. The high molecular weight polyethylene glycol has a molecular weight in the range of 600 Da to 2,000,000 Da. or various numbers in the range of 600 Da to 2,000,000 Da.

3. The method of claim 2, wherein the polyethylene glycol has a number average molecular weight of 100 or more. Soft gel composition.

17. The plasticizer is present in the softgel capsule shell composition.

3. The composition of claim 2, wherein the amount of the hydroxybenzoate is about 0.5 wt. % to about 40 wt. % based on the total weight of the composition.

1. The softgel composition described herein.

18. The buffering agent is present in the softgel capsule shell composition.

5. The method of claim 4, wherein the amount of the hydroxybenzoate is about 0.1 wt. % to about 5 wt. % based on the total weight of the composition. The softgel composition described above.

19. The buffering agent may be dibasic sodium phosphate, monobasic sodium phosphate, sodium bicarbonate, Sodium citrate, disodium phosphate, calcium phosphate, dibasic calcium phosphate, Tricalcium phosphate, monopotassium phosphate, dipotassium phosphate, and combinations thereof 5. The softgel composition of claim 4, wherein the softgel composition is selected from the group consisting of:

20. 1. A softgel composition comprising a fill material comprising an active pharmaceutical agent or a cosmetic agent, said fill material is encapsulated by a shell composition, and the shell composition comprises a non-animal derived gelling agent and and a water-soluble polymer, wherein the shell composition is dissolved in 900 mL of 0.1 N HCl and and when subjected to dissolution in USP Apparatus II using paddles at 75 RPM in deionized water The softgel composition completely dissolves in less than 30 minutes.

21. 1. A softgel composition comprising a fill material encapsulated by a shell composition, said shell comprising: The composition is a non-animal derived gelling agent comprising carrageenan, starch, or a combination thereof; and Polyvinyl alcohol, pullulan gum, polylactic acid, polyvinyl alcohol-polyethylene Glycol graft copolymer, high molecular weight polyethylene glycol, povidone, surfactant a water-soluble polymer containing an agent, or a combination thereof The salt gel composition comprising:

22. The filling material comprises a hydrophilic material, a lipophilic material, an amphiphilic material, or a combination thereof.

22. The softgel composition of claim 20 or 21.

23. 23. The method of claim 20, wherein the shell composition comprises a surfactant. Soft gel composition.

24. 24. The method of claim 20, wherein the filling material is a solution, a suspension, a semi-solid, or a solid.

10. The softgel composition of claim 1 .

25. 25. The method of claim 21, wherein the filler material comprises an active pharmaceutical agent or a cosmetic agent.

1. The softgel composition described herein.

26. a non-animal gelling agent, a water-soluble polymer, and optionally a buffer, plasticizer, or water sac blending at least one of them to form a blend; and encapsulating a filler material in a shell composition comprising said blend; 1. A method for preparing a softgel composition comprising:

27. The composition is mixing a plasticizer with water to form a plasticizer solution; and A water-soluble polymer, a non-animal gelling agent, and a buffering agent are mixed with the plasticizer solution to form a formulation. To form 27. The method of claim 26, comprising:

28. The composition is mixing a plasticizer, a non-animal gelling agent, and water to form a plasticizer solution; mixing a water-soluble polymer and a buffer with said plasticizer solution to form a formulation; 27. The method of claim 26, comprising:

29. 28. The method of claim 26 or 27, further comprising heating the blend to form a molten mass. How to post.

30. 30. The method of claim 29, wherein the molten mass is homogeneous.

31. 31. The method of claim 29 or 30, further comprising extruding the molten mass to form a ribbon. The method described.

32. The ribbon may be about 0.001 inches to about 0.050 inches (about 0.0254 mm to about 1 32. The method of claim 31 , wherein the substrate has a thickness in the range of 0.27 mm.

33. 26. A method of treating a condition comprising administering to a subject a softgel composition according to any one of claims 1 to 25. A composition or softgel prepared according to the method of any one of claims 26 to 32. and administering the composition to a subject in need thereof, wherein said condition is treated by administration. A method for treating, preventing, ameliorating, or alleviating a disease.

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