Capsules with sunscreen

Abstract

The present invention provides ingestible dosage form articles, such as opaque capsules, having reduced light transmission.

Description

[0001] This application is a divisional application of the invention patent application with application number 201980032910.9, application date May 14, 2019, applicant is Belgian Capsule Company, and invention name is “Capsule containing sunscreen”. Technical Field

[0002] The present disclosure relates to formulations for making opaque capsules or capsule shells and opaque capsules made therefrom. The capsules protect the contents from light while maintaining good mechanical properties. The present invention also relates to methods for making such capsules and their use for delivering the contents. Background of the Invention

[0003] Certain drugs or other active ingredients (such as health foods) are sensitive to light degradation and need to be stored in a light-shielding manner. Therefore, within the capsule, the opacity of the capsule regulates the light-shielding properties. Typically, titanium dioxide (TiO2) is used in the prior art to create opacity in the capsule shell.

[0004] Driven by the constant search for new products, people seek alternatives to well-known sunscreens.

[0005] There are many opacifiers, but due to their limited opacifying capacity, not all opacifiers can provide capsules with good opacifying properties while maintaining the mechanical strength required for production, processing and filling of active ingredients.

[0006] CaCO₃ is defined as one of many potential opacifiers, light-blocking agents, light-blocking materials, or pigments in numerous patents and patent applications, such as EP1580229A1, WO2011143347, WO2015174868A1, EP1502588A1, US3784684, EP1757275A1, JP2003300872A, US200244970A1, and US20100021535A1. However, none of these documents describe experimental success in achieving a light-blocking effect and maintaining mechanical strength when CaCO₃ is incorporated into the capsule formulation itself, rather than being applied to the capsule shell support in some form. EP1574220A1 discloses the use of calcium lactate as a light-blocking agent in HPMC-based capsules. However, this calcium lactate has a relatively low refractive index and therefore does not result in sufficient opacity. No information is given about the mechanical strength of this capsule.

[0007] It is therefore an object of the present invention to provide capsules having light-blocking capabilities without the need for TiO2 and still maintaining good mechanical properties. Summary of the Invention

[0008] The present invention relates to capsule shell formulation design, which focuses on the selection of a light-shielding agent that reduces the light transmittance of the capsule while maintaining the mechanical stability required for the production, storage, processing, filling, etc. of the capsule.

[0009] The inventors have determined that calcium carbonate (CaCO 3 ) provides the capsule with an optimal balance between good opacity and good mechanical properties when present in a specific concentration range, ie, provides the capsule with an optimally balanced level of opacity and mechanical strength.

[0010] This was unexpected because there have been many publications reporting on the potential use of calcium carbonate as a sunscreen, but no real results have been shown regarding opacity and mechanical strength when sunscreens are incorporated into capsule-forming formulations.

[0011] After extensive research on this problem, the inventors have now come up with the following aspects of the present invention:

[0012] Aspect 1. A capsule-forming composition comprising:

[0013] a film-forming agent selected from the group consisting of gelatin, polysaccharides, modified starches, cellulose derivatives or synthetic polymers or combinations thereof; and

[0014] The sunscreen is in the form of calcium carbonate, preferably precipitated calcium carbonate, present in an amount of 3 to 10% by weight based on the dry weight of the capsule-forming formulation.

[0015] Aspect 2. The capsule-forming composition according to aspect 1, wherein the sunscreen is present in an amount of 4 to 8 wt%, more preferably 5 to 7 wt%, such as 4.5 to 6.5 wt%, based on the dry weight of the capsule-forming formulation.

[0016] Aspect 3. The capsule-forming composition according to aspect 1 or 2, wherein the calcium carbonate has a substantially round or prismatic particle shape. In a particular embodiment, the calcium carbonate comprises small round or prismatic uniform particles.

[0017] Aspect 4. The capsule-forming composition according to any one of aspects 1 to 3, wherein the CaCO 3 has a median particle size of 0.2 to 2.0 μm, or has a D 4,3 particle size of about 10 μm or less.

[0018] The average particle size may be expressed as "D50" (Dv50) with a median particle diameter of 0.2 to 2 μm, for example 0.5 to 1.5 μm, more preferably 0.3 to 1.2 μm, more preferably 0.4 to 1.1 μm, for example about 1 μm.

[0019] Alternatively, the particles may have a "D4,3" particle size of about 10 μm or less, more preferably about 8 μm or less, such as about 6 μm or less, or about 4 μm or less, more particularly 1 μm to 10 μm, or 1-8 μm, preferably 2-6 μm, more preferably about 4 μm, such as 3.5 to 4.5 μm.

[0020] In one embodiment, the particle size distribution is defined as a particle size distribution span that is as small as possible. Preferably, the span is less than 15, such as less than 10, preferably less than 8, more preferably less than 6.

[0021] Aspect 5. The capsule-forming composition according to any one of aspects 1 to 4, having a calcium carbonate concentration of about 10%, will typically have an opacity factor of 20% or greater. The capsule-forming composition according to any one of aspects 1 to 4, having a calcium carbonate concentration of about 5%, will typically have an opacity factor of 15% or greater. Alternatively, the capsule-forming composition according to any one of aspects 1 to 4, when the capsule contains 10% calcium carbonate, has a light transmittance of 35% or less at 650 nm; or when the capsule contains 5% calcium carbonate, has a light transmittance of 55% or less at 650 nm.

[0022] Aspect 6. The capsule-forming composition according to any one of aspects 1 to 5, wherein the calcium carbonate is in the form of precipitated calcium carbonate.

[0023] Aspect 7. The capsule-forming composition according to any one of aspects 1 to 6, wherein the film-forming agent is a cellulose-based polymer, such as methylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose or a combination thereof, preferably hydroxypropylmethylcellulose.

[0024] Aspect 8. The capsule-forming composition according to any one of aspects 1 to 6, wherein the film-forming agent is a synthetic polymer, such as polyvinyl alcohol, polyethylene glycol / polyethylene oxide, polyvinyl acetate, polyacrylamide, polyvinyl acetal diethylamino acetate, aminoalkyl methacrylate copolymer E, polyvinyl pyrrolidone, or a combination thereof.

[0025] Aspect 9. The capsule-forming composition according to any one of aspects 1 to 6, wherein the film-forming agent is a polypeptide (protein)-based polymer, such as gelatin, collagen, zein, casein, soy protein or mung bean protein, whey protein, pea protein.

[0026] Aspect 10. The capsule-forming composition according to any one of aspects 1 to 6, wherein the film-forming agent is a polysaccharide, preferably pullulan, starch, cellulose or dextran.

[0027] Aspect 11. The capsule-forming composition according to any one of aspects 1 to 6, wherein the film-forming agent is an acrylate and / or (meth)acrylate-based polymer, such as ethyl acrylate-methyl methacrylate copolymer, polyacrylic acid or polymethyl methacrylate.

[0028] Aspect 12. The capsule-forming composition according to any one of aspects 1 to 11, further comprising one or more additives, for example: a gelling agent, a gelling aid, a viscosity modifier, a defoaming aid, a plasticizer, a lubricant, a colorant, a solvent, a solvent aid, a surfactant, a dispersant, a solubilizer, a stabilizer, a flavoring agent, a sweetener, an adsorbent, an adherent, an antioxidant, an antiseptic, a preservative, a desiccant, a flavoring agent, a fragrance, an antioxidant, a pH adjuster, a binder, a disintegrant, a release controlling agent.

[0029] Aspect 13. A capsule formed from the capsule-forming composition according to any one of aspects 1 to 12.

[0030] Preferably, the capsule comprises:

[0031] a film-forming agent selected from the group consisting of gelatin, a polysaccharide, a modified starch, a cellulose derivative or a synthetic polymer; and

[0032] The sunscreen in the form of calcium carbonate is present in an amount of 3 to 10 wt % based on the dry weight of the capsule-forming composition, preferably 4 to 8 wt %, more preferably 5 to 7 wt %, for example 4.5 to 6.5 wt % based on the dry weight of the capsule-forming composition.

[0033] In a preferred embodiment, when the capsules contain HPMC as the film-forming agent, the finished capsules will contain 4 to 6 wt% water, based on the total weight of the capsule. In another preferred embodiment, when the capsules contain gelatin as the film-forming agent, the finished capsules will contain 12 to 15 wt% water, based on the total weight of the capsule. These concentrations are based on ambient temperature and humidity (25°C (+ / - 2°C) and 30-50% relative humidity).

[0034] Aspect 14. The capsule according to aspect 13, which is a hard shell capsule, preferably a hard shell capsule based on gelatin, pullulan or HPMC.

[0035] Aspect 15. A method of producing capsules with reduced light transmittance (also referred to as opaque capsules), comprising providing a film-forming composition according to any one of claims 1 to 12, and forming capsules using a dip coating process.

[0036] Aspect 16. A method for preparing the film-forming composition according to any one of aspects 1 to 12, comprising the steps of:

[0037] a) preparing an aqueous dispersion of a calcium carbonate sunscreen by mixing;

[0038] b) preparing a film-forming formulation comprising one or more film-forming agents selected from the group consisting of gelatin, polysaccharides, modified starches, cellulose derivatives or synthetic polymers or a combination thereof;

[0039] c) adding the aqueous dispersion of step a) to the solution of step b); and

[0040] d) mixing the dispersion obtained in step c) to obtain a film-forming composition comprising 3 to 10 wt.% CaCO3, preferably 4 to 8 wt.%, more preferably 5 to 7 wt.%, for example 4.5 to 6.5 wt.% CaCO3, based on the final dry weight of the film-forming composition. In one embodiment, the film-forming composition comprises 15-25 wt.% HPMC, for example 20.5 wt.% HPMC; or 25-35 wt.% gelatin, for example about 31 wt.% gelatin, based on the total dry weight of the final capsule-forming formulation.

[0041] Aspect 17. The method according to aspect 16, wherein step c) is performed in two steps: c1) adding a portion of the film-forming formulation of step b) to the dispersion of step a) to form a slurry, and c2) adding the slurry to the remaining film-forming formulation. Preferably, the slurry is formed using high shear mixing, for example, mixing at a speed of at least 10,000 rpm, for example, at a speed of 12,000 rpm or more, for at least 2 minutes.

[0042] Aspect 18. The method according to aspect 16 or 17, wherein the mixing in step a) comprises high shear mixing, for example, mixing at a speed of at least 15,000 rpm, preferably at least 20,000 rpm, for at least 4 minutes.

[0043] Aspect 19. The method according to any one of aspects 16 to 18, wherein the film-forming agent comprises gelatin, pullulan, HPMCAS or HPMC.

[0044] In addition, the film-forming solution may further comprise one or more additives, for example: gelling agents, gelling aids, viscosity regulators, defoaming aids, plasticizers, lubricants, colorants, solvents, solvent aids, surfactants, dispersants, solubilizers, stabilizers, flavoring agents, sweeteners, adsorbents, adhesives, antioxidants, bactericides, preservatives, desiccants, fragrances, perfumes, antioxidants, pH regulators, binders, disintegrants, and release control agents.

[0045] Aspect 20. The method according to any one of aspects 16 to 19, wherein the sunscreen is present in an amount of 4 to 8 wt%, more preferably 5 to 7 wt%, based on the final dry weight of the film-forming formulation.

[0046] Aspect 21. A method for preparing a capsule, comprising the following steps:

[0047] a) preparing a film-forming composition according to the method of any one of aspects 16 to 20, and

[0048] b) Capsules are produced by dip molding. Generally, this dip molding method comprises the following steps: dipping a mold pin into a film-forming composition at a sufficient temperature to form a film on the dip pin; drying the film on the dip pin (air drying); and removing the film-forming capsule half from the dip pin.

[0049] Aspect 22. The capsule according to aspect 13 or 14, or the capsule obtained by the method of aspect 21, wherein:

[0050] When the capsule is an HPMC capsule with a calcium carbonate concentration of about 5 or 10%, its opacity factor is generally 20% or higher. The transmittance of HPMC capsules with 5% CaCO3 at 650nm is generally 35% or lower, while the transmittance of HPMC capsules with about 10% CaCO3 at 650nm is generally 10% or lower.

[0051] When the capsule is an HGC capsule having a calcium carbonate concentration of about 5 or 10%, its opacity factor is generally 17% or higher. The transmittance of HGC capsules with 10% CaCO3 at 650 nm is generally 30% or lower, while the transmittance of HGC capsules with about 5% CaCO3 at 650 nm is generally 55% or lower.

[0052] These values ​​are based on the average capsule wall thickness of standard capsules, which is approximately 100 μm.

[0053] Aspect 23. The capsule according to aspect 22, which is filled with a filling formulation comprising an active ingredient such as a nutrient or a drug.

[0054] Aspect 24. The capsule according to aspect 23, wherein the active ingredient is present in an amount of about 0.05 wt % to about 100 wt % based on the total dry weight of the fill formulation. Typically, the active ingredient may be present in an amount of about 0.5 wt % to about 90 wt %, preferably about 1 wt % to about 50 wt %, and more preferably about 5 wt % to about 30 wt %, based on the total dry weight of the fill formulation.

[0055] Aspect 25. The capsule according to any one of aspects 23 or 24, wherein the active ingredient is an active pharmaceutical ingredient, a nutritional supplement, a nutraceutical, a vitamin, a mineral, a cosmetic, a health food, preferably a photolabile active ingredient.

[0056] BRIEF DESCRIPTION OF THE DRAWINGS

[0057] Figure 1 : SEM images of different types of CaCO3 particles: A) precipitated CaCO3 presents small uniform round / prismatic particles; B) CaCO3 encapsulated in capsules presents agglomerated particles forming large particles (up to 100 μm). DETAILED DESCRIPTION

[0058] Developing dosage forms (eg capsules) with limited light transmittance, for example to protect photolabile active ingredients, is often a balance between opacity and mechanical strength and stability of the capsule shell.

[0059] The present inventors have now identified a concentration range and type of calcium carbonate that provides a good balance to achieve good light blocking effect and mechanical strength.

[0060] It is to be understood that the terminology used herein is not intended to limit the present invention, since the scope of the present invention will be limited only by the appended claims.

[0061] As used herein, the singular forms "a," "an," and "the" include singular and plural referents unless the context clearly dictates otherwise.

[0062] As used herein, the terms "comprising," "comprises," and "comprised of" are synonymous with "including," "includes," or "containing," "contains," and are inclusive or open-ended and do not exclude additional, undescribed members, elements, or method steps. The terms also encompass "consisting of" and "consisting essentially of."

[0063] The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within each range, as well as the recited endpoints.

[0064] The term "about" as used herein, when used in reference to a measurable value such as a parameter, amount, duration, and the like, is meant to encompass variations and / or differences in the specified value, particularly those variations and / or differences that would be perceived by one of ordinary skill in the art to be a reasonable amount of deviation in light of the nature of the specified value, i.e., +10% or less, preferably + / -5% or less, more preferably + / -1% or less, still more preferably + / -0.1% or less, of the specified value, within a range of values that is suitable to practice the application of the present disclosure. It is understood that the numerical values of the modifier "about" are also specifically disclosed as preferred amounts that themselves and also as being preferred in and of themselves.

[0065] Although the term "one or more" (e.g. one or more members of a group of members) is clear per se, by way of further illustration, the term includes inter alia a reference to any one of the recited members, or to any two or more of the recited members, e.g. any >3, >4, >5, >6 or >7 etc. of the recited members, and up to all of the recited members.

[0066] The expression "low light transmission" when used in combination with a capsule or a capsule formulation means that the capsule or capsule formulation allows for limited light transmission, and is thus capable of blocking light (e.g. natural or artificial light) to some extent from entering the chamber of the capsule body containing the active ingredient. For a capsule containing 10 wt% of precipitated CaCO3in its shell, it is generally contemplated that the opacity factor is about 20% or more, e.g. 25% or more, or 35% or more. Alternatively, the light transmission can be indicated and implies the amount of light that is allowed to enter through the capsule shell. Generally, it is contemplated that the light transmission at 650 nm is below 35%, preferably below 25%, e.g. about 20% or less, or about 10% or less. For a capsule containing 5 wt% of precipitated CaCO3in its shell, it is generally contemplated that the opacity factor is about 15% or more. Alternatively, the light transmission factor can be indicated and implies the amount of light that is allowed to enter through the capsule shell. Generally, it is contemplated that the light transmission at 650 nm is below 55%.

[0067] The opacity and light transmission of the capsules of the present application depend on the type of film forming polymer used and the concentration of CaCO3used. As an exemplary guidance:

[0068] When the capsule is an HPMC capsule having a calcium carbonate concentration of about 5 or 10%, it is generally contemplated that the opacity factor is 20% or more. An HPMC capsule having 5% CaCO3generally has a light transmission at 650 nm of 35% or less, while an HPMC capsule having about 10% CaCO3generally has a light transmission at 650 nm of 10% or less;

[0069] When the capsule is an HGC capsule having a calcium carbonate concentration of about 5 or 10%, the opacity factor is generally 17% or higher. The transmittance of an HGC capsule having 10% CaCO3 at 650 nm is generally 30% or lower, while the transmittance of an HGC capsule having about 5% CaCO3 at 650 nm is generally 55% or lower.

[0070] These values ​​are based on the average capsule wall thickness of standard capsules, which is approximately 100 μm. There are several methods for measuring particle size and particle size distribution. Some are light-based, others ultrasound-based, or based on electric fields, gravity, or centrifugal forces.

[0071] In all methods, size is an indirect measure, obtained by a model that abstracts the true particle shape into a simple and standardized shape, such as a sphere (most common) or a cuboid (when using a minimum bounding box), where size parameters (such as the diameter of a sphere) are meaningful. Mathematical morphology methods are an exception, which do not require shape assumptions.

[0072] Defining the particle size of an ensemble (collection) of particles raises another question. Real systems are almost always polydisperse, meaning that the particles within the ensemble have different sizes. The concept of particle size distribution reflects this polydispersity. A certain average particle size is often required for an ensemble of particles.

[0073] The term "D50 average particle size" or "Dv50" or volume-based median particle size indicates that in a mixture of particles, 50% (by mass) of the particles have a diameter less than the indicated D50 average particle size, and the other 50% (by mass) of the particles have a diameter greater than the indicated D50 average particle size. Common measurement techniques are sieve analysis, direct imaging, and laser diffraction, which are known in the art.

[0074] The term "D4,3 mean diameter size" or volume mean diameter (also known as the DeBroukere mean, following the conventional method in ref. 2, ASTM E 799) is the average particle size based on the volume distribution, indicating that the volume mean is used to define the center point of the particle size distribution, although the median is more commonly used than the mean when using this technique. The value of D[4,3] is strongly affected by the presence of aggregates, which are not easily broken up during the measurement, resulting in large variations in the measured particle size within a larger range of particles. The formula is as follows:

[0075]

[0076] The term "particle size distribution" reflects the width or breadth of the distribution of particle sizes. Several calculations are used to describe the width of the distribution, but the most common calculations are the standard deviation and variance.

[0077] The term "particle size span" refers to the width of the particle size distribution and follows the following formula: Span = (Dv0.9-Dv0.1) / Dv0.5, where Dv0.9 (D90), Dv0.1 (D10) and Dv0.5 (D50) represent the sizes below which 90%, 10% and 50% of the particles are respectively measured by laser diffraction.

[0078] The term "high shear mixing" encompasses any type of high shear mixing at a speed of at least 15,000 rpm, preferably at least 20,000 rpm, for at least 4 minutes. As a non-limiting example, an IKA Ultra Turraxx T25 mixer can be used. The concentration of the dispersion is preferably at least 15% by weight, preferably greater than 20% by weight.

[0079] All documents cited in this specification are incorporated herein by reference in their entirety.

[0080] Unless otherwise specified, all terms used to disclose the present invention, including technical and scientific terms, have the meanings commonly understood by those skilled in the art to which the present invention belongs. By way of further guidance, term definitions may be included to better understand the teachings of the present invention.

[0081] The film-forming agent referred to herein may be any type of film-forming agent. Particularly contemplated film-forming agents are gelatin, polysaccharides, modified starches or synthetic polymers. Non-limiting examples thereof include generally known agents, such as: cellulose-based polymers such as methylcellulose, ethylcellulose, methylhydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, etc., polysaccharides such as pullulan, carrageenan, gellan gum, alginate, etc.; or gelatin; synthetic polymers such as polyvinyl alcohol, polyvinyl acetal diethylaminoacetate, methacrylate aminoalkyl ester copolymer E (Eudragit-E-Rohm Pharma Co. Ltd.), polyvinyl pyrrolidone, etc.; (meth)acrylate-based polymers such as ethyl acrylate-methyl methacrylate copolymer suspension (Eudragit NE (trade name), Rohm Pharma Co. Ltd.), etc.; acrylate-based polymers such as methacrylate copolymer L (Eudragit L-Rohm Pharma Co. Ltd.), methacrylate copolymer LD (Eudragit L-30D55-Rohm Pharma Co. Ltd.), etc. Pharma Co. Ltd.), etc.; and any combination thereof.

[0082] Gelatin, pullulan and cellulose-based polymers are preferred. Among the cellulose-based polymers, methylhydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and hydroxypropylmethylcellulose acetate succinate are more preferably used.

[0083] In addition to the film-forming agent, other additives may be added, such as plasticizers, colorants, solvents, solvent aids, dispersants, solubilizers, stabilizers, flavorings, sweeteners, adsorbents, absorbents, adhesives, antioxidants, bactericides, preservatives, desiccants, flavorings, fragrances, pH adjusters, binders, lubricants, wetting agents, disintegrants and / or release control agents known in the art.

[0084] It may be advantageous to add additives such as dispersants (for example (iota-)carrageenan, sodium lauryl sulfate, sorbitan or lecithin).

[0085] When hard capsule shells are contemplated, the capsule shells may optionally further include other minor components conventionally used in capsules, or other minor components used in aqueous compositions for impregnation and retained as part of the finished capsule. Examples of such materials include surfactants, antifoaming aids, antioxidants, viscosity modifiers, gelling agents, gelling aids, lubricants, and plasticizers.

[0086] The production of hard capsule shells by non-thermal gel dipping processes typically relies on so-called "setting systems" containing gelling agents and / or gelling aids to impart adequate setting capabilities while cooling into film-forming polymers (pullulan, HPMC, or starch derivatives) that inherently have poor gelling properties under these conditions. The setting system sets the aqueous composition on an immersed pin, thereby facilitating capsule production and ensuring uniform capsule shell thickness.

[0087] Such gelling agents and adjuvants are well known in the art. In terms of the film-forming polymers used in the manufacture of capsule shells, we refer to, for example, U.S. Patent No. 5,264,223 and EP714656 (discussing HPMC capsules), EP1117736 (discussing starch derivative capsules); WO2005105051 and EP1072633 (discussing pullulan capsules).

[0088] In one embodiment, the styling system of the present invention comprises one or more gelling agents.In one embodiment, the styling system of the present invention comprises one or more gelling agents and one or more gelling aids, also known as co-gelling agents.

[0089] In one embodiment, the one or more gelling agents are selected from the group consisting of alginates, agar gum, guar gum, locust bean gum (carob), carrageenan (preferably kappa, lambda, and / or iota carrageenan), tara gum, gum arabic, ghatti gum, khaya grandifolia gum, goat thorn gum, karaya gum, pectin, arabic (arabinan), xanthan gum, low acyl gellan gum and high acyl gellan gum, starch, konjac mannan, galactomannan, funoran, acetan, welan gum, rhamnan, furcellan, succinoglycan, scleroglycan, schizophyllan, tamarind gum, curdlan, dextran, and mixtures thereof. Preferably, the one or more gelling agents are selected from carrageenan (preferably kappa- and / or iota-carrageenan, more preferably at least kappa-carrageenan), gellan gum, and mixtures thereof. In one embodiment, the one or more gelling agents comprise carrageenan (preferably kappa- and / or iota-carrageenan, more preferably at least kappa-carrageenan), preferably consist of carrageenan (preferably kappa- and / or iota-carrageenan, more preferably at least kappa-carrageenan). In one embodiment, the one or more gelling agents include gellan gum, preferably consist of gellan gum.

[0090] In one embodiment, the one or more gelling agents comprise a combination of two or more of the agents listed above. In one embodiment, the one or more gelling agents comprise, and preferably consist of, a combination of xanthan gum and locust bean gum. In one embodiment, the one or more gelling agents comprise, and preferably consist of, a combination of xanthan gum and konjac mannan.

[0091] In one embodiment, the one or more gelling aids (also called co-gelling agents) are cationic. In one embodiment, the one or more gelling aids are selected from: K + ,Li + ,Na + ,NH4 + ,Ca 2+ ,Mg 2+ and mixtures thereof. Preferably, one or more gelling aids are selected from: K + ,NH4 + ,Ca 2+ and mixtures thereof. The cations may be added to the styling system in the form of pharmaceutically or food-acceptable water-soluble salts such as chlorides, acetates, citrates or phosphates.

[0092] In one embodiment, the styling system of the present invention comprises one or more gelling agents selected from the group consisting of carrageenan (preferably kappa and / or iota-carrageenan, more preferably at least kappa-carrageenan), gellan gum and mixtures thereof; and one or more pharmaceutically or food acceptable K + ,NH4 + ,Ca 2+ and water-soluble salts of mixtures thereof.

[0093] In one embodiment, the aqueous composition of the present invention comprises one or more gelling agents as defined above in an amount suitable for obtaining a hard capsule shell as defined below, the hard capsule shell comprising from about 0.01% to 3.0% by weight, preferably from about 0.03% to 1.0% by weight, and preferably from about 0.1% to 0.5% by weight of such gelling agent relative to the weight of the hard capsule shell. Exemplary amounts of suitable gelling agents are readily available to those skilled in the art of hard capsule manufacturing. For example, it is generally recognized that a hard capsule shell containing a "target" amount of gelling agent within the above-mentioned range can be obtained by using a dip molding process using an aqueous composition containing about 1 / 4 (i.e., 25%) of the "target" amount (expressed as a % by weight relative to the weight of the composition).

[0094] In one embodiment, the aqueous composition of the present invention comprises one or more gelling aids as defined above in an amount suitable for obtaining a hard capsule shell as defined below, the hard capsule shell comprising less than about 3%, preferably less than about 2.0%, more preferably from about 0.5% to 2.0%, and even more preferably from about 1.0% to 2.0% of the one or more gelling aids relative to the weight of the hard capsule shell. In the case where the gelling aid is a cation, the above ranges are expressed as the weight of a pharmaceutically or food-acceptable water-soluble salt containing the cation relative to the weight of the capsule shell. Those skilled in the art of hard capsule manufacturing can readily obtain exemplary amounts of suitable gelling aids. For example, it is generally accepted that when water is about 75% by weight relative to the weight of the aqueous composition, a hard capsule shell containing a "target" amount of gelling aid can be obtained by using an aqueous composition containing about 1 / 4 (i.e., 25%) of the target amount (expressed as a % by weight relative to the weight of the composition) by a dip molding process.

[0095] The hard capsule shell may also contain residual water. Typically, such shells contain, for example, less than 25% by weight, preferably less than 20% by weight, more preferably from 0% to 14% by weight, even more preferably from greater than 1% to less than 10% by weight, and more preferably from 2% to 7% by weight of water.

[0096] Although any active ingredient selected from active pharmaceutical ingredients, nutritional supplements, nutraceuticals, vitamins, minerals, cosmetics, health foods, etc. can be encapsulated in the capsule preparation of the present invention, photolabile or photosensitive ingredients are particularly suitable. Non-limiting photolabile drugs that can be filled in the capsule to obtain an effective light-shielding effect when they are filled into the capsule preparation of the present invention include: dihydropyridine derivatives (e.g., nifedipine), antiviral HIV protease inhibitors (e.g., ritonavir, saquinavir), hyperlipidemia therapeutic agents (e.g., clofibrate), iodine compounds (e.g., sodium ipodate),

[0014] Examples of the present invention include iopodate, sodium iodide), polyunsaturated fatty acid derivatives (e.g., ethyl eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)), carotenoids (e.g., lycopene, nopaline, β-carotene, lutein, lutein), ubiquinone (coenzyme Q) (e.g., ubidecarenone used as a metabolizable cardiotonic), various vitamin derivatives, as well as indomethacin, colchicine, diazepam, syrosingopine, norethindrone, piretanide, cyanthiazide, perphenazine, mequinazine, medazepam, menatetrenone, indenolol hydrochloride, reserpine, sofarone, bromocriptine mesylate, bufetolol hydrochloride, and propranolol hydrochloride. Among the vitamin derivatives, fat-soluble vitamin derivatives are preferably used. Examples include vitamin A derivatives (e.g., tretinoin, hepatic oil, retinyl palmitate), vitamin A analogs (e.g., etretinate), vitamin D derivatives, vitamin E derivatives (e.g., tocopheryl nicotinate, tocopheryl acetate, tocopheryl calcium succinate), and vitamin K derivatives (e.g., phylloquinone (vitamin K1), vitamin K2 (menaquinone), vitamin K3 (menadione), menatetrenone, phylloquinone).

[0097] The medicine as active ingredient can be filled into the capsule of the present invention alone or in combination with any matrix or carrier, additive or excipient. Any type of matrix (base) or carrier can be used, whether fat-soluble or water-soluble, as long as the activity of the medicine is not damaged and the various physical properties (such as strength, air permeability and disintegration, or dissolution characteristics) of the capsule shell are not affected. Similarly, the matrix itself can be liquid or solid at room temperature, as long as it can be filled into the capsule by means of heating or diluting with other solvents. Examples of such matrix include vegetable oils (e.g., soybean oil, sesame oil, cottonseed oil, olive oil), fatty acid glycerides (e.g., medium-chain triglycerides), propylene glycol, propylene glycol fatty acid esters, polyethylene glycol, polyvinyl pyrrolidone, triacetin, liquid paraffin, polyoxyethylene sorbitan fatty acid esters, sucrose fatty acid esters, ethanol and purified water, which can be used alone or in combination. Preferred matrices for dissolving fat-soluble drugs (e.g., vitamins A, D, E and K) are vegetable oils or fatty acid glycerides, particularly preferably medium-chain triglycerides. When a water-soluble matrix is ​​used, it is preferred to provide a protective layer or a crystallization inhibitor between the shell layer and the drug layer in consideration of the effect on the capsule shell.

[0098] The drug filled into the capsule shell of the present invention is preferably, but not limited to, a drug in liquid form or a drug dissolved, suspended or emulsified in the above-mentioned matrix. The drug can also be in solid form (e.g., powder, granules) or semi-solid form (e.g., cream or gel).

[0099] Therefore, the present invention provides a capsule formulation for forming a capsule with reduced light transmittance (also known as an opaque capsule), comprising:

[0100] a film-forming agent as defined herein; and

[0101] The sunscreen in the form of calcium carbonate is present in an amount of 3-10 wt % based on the dry weight of the capsule forming formulation. Preferably, the amount of CaCO3 present is 4-8 wt % based on the dry weight of the final capsule forming formulation, more preferably 4-8 wt % based on the dry weight of the final capsule forming formulation.

[0102] 4.5-6.5 wt%.

[0103] As will become clear from the Examples section, the amount and particle size of calcium carbonate and the type of CaCO 3 influence the balance between opacity and mechanical strength of the films and capsules contemplated herein.

[0104] The inventors have found that a median particle size (Dv50) of 0.2 to 2.0 μm and / or a "D4,3" particle size of about 10 or less is particularly advantageous for forming such films and capsules.

[0105] The average particle size may be expressed as a "D50" (Dv50) median particle diameter of 0.2 to 2 μm, for example 0.5 to 1.5 μm, more preferably 0.3 to 1.2 μm, more preferably 0.4 to 1.1 μm, for example about 1 μm.

[0106] Alternatively, the particles may have a "D4,3" particle size of about 10 μm or less, more preferably about 8 μm or less, such as about 6 μm or less, or about 4 μm or less, more particularly 1 μm to 10 μm, or 1-8 μm, preferably 2-6 μm, more preferably about 4 μm, such as 3.5 to 4.5 μm.

[0107] Preferably, the calcium carbonate has a substantially round / prismatic particle shape. In a particular embodiment, the calcium carbonate comprises small uniform round or prismatic particles.

[0108] Typically, the span of the particle size distribution of the CaCO3 particles as defined above is as low as possible. Preferably, the span is less than 10, preferably less than 8, more preferably less than 6.

[0109] In a preferred embodiment, CaCO3 is precipitated, i.e., prepared from calcium oxide (CaO-lime), to which water is added to obtain calcium hydroxide. Carbon dioxide is then passed through the solution to precipitate the desired calcium carbonate, which exists industrially in the form of precipitated calcium carbonate (PCC). PCC has a variety of crystal forms and sizes and can be customized to optimize performance in specific applications. Calcium oxide used as a raw material for the precipitation process can be obtained through a lime milk process, which includes crushing high-purity calcium carbonate rock into small particles or powder suitable for processing, then heating it to about 1000°C to decompose the calcium carbonate into calcium oxide (CaO) and carbon dioxide (CO2), which can be captured and reused in the above-mentioned precipitation process.

[0110] In a preferred embodiment, the PCC has a median particle size of 0.2 to 2.0 μm or a D4,3 particle size of about 10 μm or less. Alternatively, the average particle size of the PCC can be expressed as a "D50" (Dv50) median particle size of 0.2 to 2 μm, such as 0.5 to 1.5 μm, more preferably 0.3 to 1.2 μm, more preferably 0.4 to 1.1 μm, such as about 1 μm.

[0111] Therefore, the present invention provides a method for preparing a film-forming composition having light-shielding ability, the method comprising the following steps:

[0112] a) preparing an aqueous dispersion of a calcium carbonate sunscreen by mixing;

[0113] b) preparing a film-forming formulation comprising one or more film-forming agents selected from the group consisting of gelatin, polysaccharides, modified starches, (meth)acrylate-based polymers or synthetic polymers or combinations thereof;

[0114] c) adding the aqueous dispersion of step a) to the solution of step b); and

[0115] d) mixing the dispersion obtained in step c) to obtain a film-forming composition comprising 3 to 10 wt. %, preferably 4 to 8 wt. %, more preferably 5 to 7 wt. %, for example 4.5 to 6.5 wt. % of CaCO 3 , based on the final dry weight of the film-forming composition. In one embodiment, the film-forming composition comprises 15-25 wt. % of HPMC (e.g., 20.5 wt. % of HPMC); or 25-35 wt. % (e.g., about 31 wt. %) of gelatin, based on the total dry weight of the final capsule-forming formulation.

[0116] In one embodiment, the film-forming composition comprises 15-25 wt% HPMC (eg, 20.5 wt% HPMC); or 25-35 wt% (eg, about 31 wt%) gelatin, based on the total dry weight of the final capsule-forming formulation.

[0117] In one embodiment, step c) is performed in two steps: c1) adding a portion of the film-forming formulation of step b) to the dispersion of step a) to form a slurry, and c2) adding the slurry to the film-forming formulation.

[0118] Preferably, the slurry is formed using high shear mixing, such as mixing at a speed of at least 10,000 rpm, such as 12,000 rpm or more, for at least 2 minutes.

[0119] In one embodiment, the mixing in step a) comprises high shear mixing, for example mixing at a speed of at least 15,000 rpm, preferably at least 20,000 rpm, for at least 4 minutes.

[0120] Without being bound by any theory, high shear mixing may result in better dispersion of the CaCO 3 in the film-forming composition, leading to increased mechanical strength.

[0121] In one embodiment, the sunscreen is present in an amount of 3 to 10 wt%, such as 4 to 8 wt%, more preferably 5 to 7 wt%, based on the final dry weight of the film-forming composition.

[0122] The present invention also provides a method for preparing capsules, which comprises the following steps:

[0123] a) preparing a film-forming composition as defined herein, and

[0124] b) producing the capsules, for example, by conventional methods such as extrusion, injection molding, casting, or dipping. Typically, such dipping methods include the following steps: dipping a mold pin into the film-forming composition at a sufficient temperature to form a film on the dipped pin; drying the film on the dipped pin ((hot)-air drying); and removing the film-formed capsule half from the dipped pin.

[0125] When using a concentration of 10% w / w precipitated calcium carbonate, capsules obtained by the methods described herein typically have, for example, an opacity index of about 20% or more and / or a light transmittance at 650 nm of 35% or less. When using lower concentrations of calcium carbonate, such as about 5%, an opacity index of about 17% or more and / or a light transmittance at 650 nm of 55% or less is achieved. The ranges are based on a capsule wall thickness of approximately 100 μm (e.g., 90 μm to 110 μm), as typically used in commercial capsules.

[0126] Such capsules can of course be used to deliver any type of ingredient, but are particularly suitable for active ingredients with limited photostability. Examples of active ingredients can be active pharmaceutical ingredients, nutritional supplements, nutraceuticals, vitamins, minerals, cosmetics, health foods, etc. Such ingredients can be present in an amount of 0.05% by weight to a maximum of 100% by weight. Typically, the active ingredient can be present in an amount of about 0.5% by weight to about 90% by weight based on the total dry weight of the filled formulation, preferably in an amount of about 1% by weight to about 50% by weight, more preferably in an amount of about 5% by weight to about 30% by weight based on the total dry weight of the filled formulation.

[0127] In one embodiment, the capsules using the opacifier are: HPMC-based capsules, such as plant-based capsules, such as those described in U.S. Patent No. 6,517,865, called VegiCaps or Capsules; as described in U.S. Patent No. 9,655,860 Capsules; Pullulan-based capsules, such as those described in U.S. Patent 6,887,307; or enteric-coated capsules, such as those described in WO2018 / 017799A1 and WO2013164121 Enteric coated capsules, the contents of which are incorporated herein by reference. A preferred method for producing this method is also disclosed in said patent and is incorporated herein by reference.

[0128] The present invention is further illustrated in the following non-limiting examples.

[0129] Example

[0130] Materials and methods

[0131] Mechanical strength test of membrane

[0132] The mechanical properties of the films were determined by tensile testing according to ASTM D882-02 (using an Instron 5965) on samples stored at 22°C and 50% RH and 23% RH. The films were stored under these conditions for 7 days. For most materials, you will notice that in the initial part of the test, the relationship between the applied force or load and the elongation exhibited by the sample is linear. In this linear region, the straight line obeys the relationship defined as "Hooke's Law," where the ratio of stress (σ) to strain (ε) is constant, or according to Hooke's Law:

[0133]

[0134] "E" is the slope of the line in the region where stress (σ) is proportional to strain (ε), and is called the "elastic modulus" or "Young's modulus."

[0135] Mechanical strength of capsule

[0136] As described below, test capsules were prepared from various film-forming compositions using conventional dip molding techniques. Size 0 capsules were obtained, each having a sidewall thickness of approximately 100 μm. The mechanical strength of the resulting capsules was evaluated by the in vitro test (internal impact) method. Briefly, a 100 g weight was dropped from a height of 8 cm onto the capsules (n=50), and the number of broken capsules was counted and expressed as a percentage.

[0137] The capsules were stored at room temperature at 2.5%, 10%, 23%, 33% and 45% relative humidity (RH) for 7 days. The measurements were performed at room temperature.

[0138] Opacity test

[0139] Opacity was measured using a spectrophotometer (Color Eye XTH portable spectrophotometer) using phase contrast imaging. To measure transmittance, the film sample was placed in the light path of the UV-VIS spectrophotometer and the transmittance at 650 nm was recorded. The film was kept at room temperature.

[0140] For opacity testing, films of approximately 100 μm thickness were prepared from various film-forming compositions as described below. The thickness of such films corresponds to a capsule sidewall thickness of 90-110 μm.

[0141] The term "opacity coefficient" as used herein corresponds to contrast opacity (OP), ie, the ratio between brightness or lightness measured relative to a black and white background. The OP measurement quantifies how close to opaque a nearly opaque material is.

[0142] The measurement is a two-part procedural metric where the Y (brightness or brightness) value is first measured on a sample against a black background, followed by a second Y value measurement on a sample against a white background. The resulting score is expressed as Y%, calculated as follows:

[0143] OP=Y 黑色背景 / Y 白色背景 x 100

[0144] Particle size measurement and imaging

[0145] The particle size was determined using laser diffraction (Mastersizer 2000, Malvern). The measurements were performed on dry powder dispersed using an air pressure of 2 bar.

[0146] The particles were imaged using a scanning electron microscope (SEM).

[0147] High shear mixing

[0148] High shear mixing of the opaque solution or dispersion is performed using an Ultra Turrax T25 mixer (IKA) at a speed of 21,000 rpm for at least 6 minutes. The concentration of the dispersion is at least 15% by weight, preferably greater than 20% by weight.

[0149] Example 1: Film-forming formulation design

[0150] The ability of CaCO3 to induce opacity and its effect on the mechanical strength of the formed polymer films were tested. This was done on both cellulose (HPMC)-based and gelatin-based films.

[0151] A dispersion of unencapsulated CaCO3 was first prepared and added to the film-forming formulation. The same general procedure was used for gelatin and HPMC formulations.

[0152] Briefly, 60 g of water were added to 22.45 g of precipitated CaCO 3 (PCC) and the mixture was homogenized by high shear mixing (e.g., 3 x 2 min at 21000 rpm (Ultra Turax) with 30 s pauses between each mixing).

[0153] Subsequently, a portion (e.g., 20 g) of a liquid film-forming HPMC or gelatin formulation comprising 20.5 wt% HPMC in water or 31 wt% gelatin in water is added and mixed into the dispersion over 3 minutes while stirring at 12,000 rpm (e.g., a Silverson apparatus) to form a slurry. The slurry is then mixed with the remainder of the film-forming formulation to form a film-forming composition resulting in a CaCO concentration of 10 wt% based on the final dry weight of the film-forming composition.

[0154] Encapsulated CaCC> (10% by weight based on the total dry weight of the final capsule forming formulation) was dispersed in water by stirring with a helical mixer for about 45 minutes. The required amount of the resulting dispersion was added to a liquid film forming HPMC or gelatin formulation comprising 20.5% by weight of HPMC in water or 31% by weight of gelatin in water based on the total dry weight of the final capsule forming formulation and mixed.

[0155] HPMC based films were prepared as follows: glass plates were kept at 60°C, film forming compositions comprising different amounts of CaCC> were kept at 28°C and films were then cast in a warm reservoir (40-50°C) using e.g. a TLC plate coater (CAMAG, Muttenz, CH) operated manually. The films were then dried at 60°C for about 1 hour and kept overnight at 22°C, 50% RH.

[0156] Gelatin films were formed as follows: glass plates were kept at 60°C, film forming solutions comprising different amounts of CaCC> were kept at 55°C and films were cast in a warm reservoir (about 60°C) using e.g. a TLC plate coater (Camag CH). The films were then dried at 50% RH, 22°C overnight.

[0157] The test results for HPMC and gelatin (HGC) films are listed in Table 1 below:

[0158]

[0159] * based on the dry weight of the entire final capsule forming formulation

[0160] The score 0 to 5 indicates the mechanical performance, 5 being the highest score and 0 the lowest score in terms of mechanical performance. HPMC stands for hydroxypropyl methylcellulose

[0161] HGC stands for hard gelatin capsules

[0162] The above results show that calcium carbonate shows potential as an opacifier, maintaining an acceptable mechanical strength, although some differences were observed between CaCC> with different particle sizes. Of particular interest is that encapsulated and milled CaCC> leads to a decrease in the mechanical strength of the film.

[0163] In all other experiments the term "precipitated CaCC> refers to PCC as shown in Table 1.

[0164] The particle size and shape of the different CaCC> compositions were analyzed using scanning electron microscopy (SEM) imaging. For this purpose, the particles were coated with metal and imaged using scanning electron microscopy known in the art. The scale bar is given in the images.

[0165] from Figure 1 As can be seen in Figure 2, the particle size and shape of the CaCO3 compositions tested vary greatly: Figure 1 B shows the agglomerated particles of encapsulated CaCO3, forming large particles (up to 100 μm), while Figure 1 A shows much smaller precipitated CaCO3 (PCC) particles with a small rounded / prismatic shape and a more uniform particle shape and size distribution than encapsulated CaCO3.

[0166] Next, the particle size of the different CaCO3 compositions was analyzed using the laser diffraction method described above (see Table 2).

[0167] Table 2: Particle size and shape of precipitated CaCO3 and encapsulated CaCO3

[0168]

[0169] Example 2: Testing of HPMC films and capsules:

[0170] Next, the effects of different calcium carbonate contents on the properties of films and capsules were studied.

[0171] For this purpose, the same procedure as used for the preparation of the HPMC film according to Example 1 was used, but with several calcium carbonate concentrations and types (PCC as in Tables 1 or 2, or encapsulated CaCO 3 ). 10 wt % CaCO 3 in a 20.5 wt % HPMC-based film was prepared using the following experimental protocol:

[0172]

[0173] To arrive at a film-forming composition comprising 6.5 wt% CaCO3 based on the final dry weight of the film-forming composition, step 4 of the above experimental protocol was as follows:

[0174]

[0175]

[0176] To achieve a film-forming composition comprising 5 wt% or 7.5 wt% CaCO3 based on the final dry weight of the film-forming composition, the above experimental protocol can be adjusted by varying the relative amounts of HPMC film-forming formulation and CaCO3 dispersion.

[0177] Different HPMC-based films were tested for opacity and light transmittance, and the results are listed in Table 3 below.

[0178] Table 3: Opacity and transmittance at 650 nm of HPMC films containing two concentrations of different CaCO3 types compared to transparent and TiO2 opaque films.

[0179]

[0180] The tensile properties of the films were also tested using an Instron device according to ASTM D882-02. As shown in Table 4, a comparison of HPMC capsules containing 5 wt% or 10 wt% precipitated CaCO or encapsulated CaCO did not show significant differences in tensile properties because HPMC films are inherently difficult to deform.

[0181] Table 4: Tensile properties of HPMC films with different CaCO3 concentrations

[0182]

[0183] Next, HPMC capsules were formed using conventional die dipping techniques summarized here: a size 0 dipping pin was preheated to approximately 73° C. while the dipping composition was maintained at 32° C. Size 0 capsules were made by a conventional dipping process using a preheated pin.

[0184] After impregnation, the capsules were dried with hot air at 60°C and 40% RH for 30 minutes and then at about 22°C and 50% RH for about 20 minutes.

[0185] The effects of precipitated and encapsulated CaCO3 on mechanical strength when used at 10 wt% in HPMC capsules were compared and it was clear from the tube test evaluation that precipitated CaCO3 had better mechanical properties (fewer broken capsules, see Table 5).

[0186] Table 5: Comparison of the effects of precipitated CaCO3 and encapsulated CaCO3 on the mechanical strength of HPMC-based capsules:

[0187]

[0188]

[0189] The mechanical strength of HPMC-based capsules formed using film-forming compositions containing 10 wt%, 7.5 wt% or 6.5 wt% precipitated CaCO3 (prepared according to the methods of Examples 1 and 2) was then tested using the test tube test (internal impact test) as shown above (Table 6).

[0190] Table 6: Comparison of the effects of different CaCO3 concentrations on the mechanical strength of HPMC-based capsules:

[0191]

[0192] Based on the above results, we can summarize the conditions for the effectiveness of calcium carbonate in HPMC capsules as the range of precipitated CaCO3 concentration from 3 wt% to 10 wt%, which results in capsules with acceptable opacity and mechanical strength.

[0193] Example 3: Testing on gelatin films: The film-forming composition and method of Example 1 were used to produce gelatin films.

[0194]

[0195] Opacity and transmittance at 650 nm were tested as described above and the results are summarized below in Table 7. Comparable results were obtained for precipitated CaCO3 (PCC as shown in Table 1 or 2) and encapsulated CaCO3.

[0196] Table 7: Opacity and transmittance at 650 nm of gelatin-based films

[0197]

[0198] As described above for the HPMC films, tensile tests were performed on the films and the results showed that the films containing precipitated CaCO 3 deformed more than the films containing encapsulated CaCO 3 (see Table 8).

[0199] Table 8: Tensile properties of gelatin-based films with different CaCO3 concentrations

[0200]

[0201] The film-forming composition can also be used to produce gelatin-based capsules by conventional die dipping. Briefly, a dimensionally controlled film is formed on a mold by dipping a stainless steel mold pin at room temperature (approximately 22°C) into a hot gelatin solution (e.g., approximately 45°C). After drying, this results in a half-shell wall thickness of approximately 100 μm.

[0202] Example 4: Industrial scale testing

[0203] 550,000 size 0 HPMC capsules and 625,000 size 1 HPMC capsules were prepared with good quality and acceptable opacity using the same film-forming composition as in Example 2. Thus, the overall test results were very positive.

Claims

1. A hard shell capsule forming composition comprising: a film-forming agent selected from gelatin, pullulan or a cellulose-based polymer; and The sunscreen is in the form of precipitated calcium carbonate and is present in an amount of 8-10% by weight based on the dry weight of the capsule-forming formulation.

2. The capsule-forming composition of claim 1, wherein the precipitated calcium carbonate is present in an amount of 10 wt. % based on the dry weight of the capsule-forming agent.

3. The capsule-forming composition of claim 1, wherein the precipitated calcium carbonate has a substantially round or prismatic particle shape.

4. The capsule-forming composition according to any one of claims 1 to 3, wherein the median particle size of the precipitated calcium carbonate is between 0.2 and 2.0 μm.

5. The capsule-forming composition according to any one of claims 1 to 3, wherein the film-forming agent is a cellulose-based polymer selected from the group consisting of methylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, or a combination thereof.

6. The capsule-forming composition according to any one of claims 1 to 3, wherein the film-forming agent is hydroxypropyl methylcellulose or gelatin.

7. The capsule-forming composition according to any one of claims 1 to 3, wherein the film-forming agent is pullulan.

8. A capsule formed from the capsule-forming composition according to any one of claims 1 to 7.

9. The capsule according to claim 8, which is a capsule based on gelatin, pullulan or hydroxypropylmethylcellulose.

10. A method of producing capsules having reduced light transmittance, comprising providing a capsule-forming composition according to any one of claims 1 to 7, and forming capsules using a dip-coating process.

11. A method for preparing the hard shell capsule forming composition according to any one of claims 1 to 7, comprising the following steps: a) preparing an aqueous dispersion of a precipitated calcium carbonate sunscreen agent by mixing; b) preparing a film-forming preparation comprising a film-forming agent, the film-forming agent is selected from gelatin, pullulan or a cellulose-based polymer; c) adding the aqueous dispersion of step a) to the solution of step b); d) mixing the dispersion obtained in step c) to obtain the capsule-forming composition, Wherein, the capsule-forming composition comprises 8-10 wt% of precipitated calcium carbonate based on the final dry weight of the capsule-forming composition.

12. The method according to claim 11, wherein The capsule-forming composition comprises 10 wt% precipitated calcium carbonate, based on the final dry weight of the capsule-forming composition.

13. The method according to claim 11 or 12, wherein the film-forming agent comprises gelatin, pullulan, hydroxypropyl methylcellulose acetate succinate or hydroxypropyl methylcellulose phthalate.

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