WO2019004984A2

WO2019004984A2 - A pharmaceutical formulation comprising cholecalciferol

Info

Publication number: WO2019004984A2
Application number: PCT/TR2018/050236
Authority: WO
Inventors: Umit Cifter; Urun Kandemirer
Original assignee: Biofarma Ilac Sanayi Ve Ticaret A.S.
Priority date: 2017-05-29
Filing date: 2018-05-16
Publication date: 2019-01-03
Also published as: WO2019004984A3

Abstract

The invention is related to a pharmaceutical formulation in chewable tablet form comprising an active agent cholecalciferol in the range of 600 IU to 3000 IU as a vitamin D3 source and at least one excipient in a unit tablet.

Description

A PHARMACEUTICAL FORMULATION COMPRISING CHOLECALCIFEROL

Related Technical Field of the Invention:

The invention is related to a pharmaceutical formulation in chewable tablet form comprising cholecalciferol in order to supply the need of vitamin D₃.

Prior Art:

It is known that vitamin D deficiency or insufficiency causes diseases such as common cancer, cardiovascular, metabolic syndrome, infectious, autoimmune and osteoporosis. Vitamin D is necessary for osteogenesis and balance of the minerals of calcium and phosphorus. Vitamin D may be taken with diet as ergocalciferol (vitamin D₂) which is present in plants and as cholecalciferol (vitamin D₃) which is present in animal tissues. Vitamin D takes place among fat soluble vitamins and at the same time it is a group of sterol which is hormone and hormone precursor because it can be synthesized as endogeny in proper biological medium. The most important sterols which belongs to vitamin D family is vitamin D₃, namely, cholecalciferol. Cholecalciferol is formed significantly from 7-dehydrocholesterol in the skin as a result of photochemical effect of ultraviolet B (UVB) rays of the sun. Therefore, exposing to sun sufficiently prevents vitamin D deficiency. However; although our country is rich in sunlight as a result of its geographical location, nowadays both children and adults may get diseases indicated above because they cannot take vitamin D enough during the day due to various working and education conditions. In addition, vitamin D is present mostly in fishes, livers and egg yolks among foods of animal origin. Even if sunlight and some foods are sources for vitamin D, synthesis of vitamin D in the body decreases or may not be possible in some situations. For example;

• Decreasing synthesis of vitamin D in the skin with elderliness in direct proportion to age,

• Need for sunlight long time especially in winter by people having different skin colors, · Limiting synthesis of vitamin D in the skin due to use of sun screens, • Preventing absorption of vitamin D from intestines and causing not to convert vitamin D to its active form in some medical problems.

Due to these reasons listed above and so on, it is quite important to use vitamin D, especially vitamin D₃, as a vitamin support. In the state of the art, there are products in pharmaceutical or pharmaceutically acceptable forms comprising cholecalciferol namely vitamin D₃ in certain amounts or percentages. Pharmaceutically acceptable forms may be in tablets, film coated tablets, chewable tablets, oral drops.

The chemical structure of cholecalciferol is as below:

Formula: The chemical structure of cholecalciferol

In the patent document of CN106420808 (A) in the state of the art, a pharmaceutical compound comprising vitamin D₃, calcium carbonate and pharmaceutically acceptable excipients and specifically a preparation method for this compound are mentioned. Vitamin D₃ is in combination with calcium carbonate in the said document.

In another patent document of CN 106333961 in the state of the art, a vitamin D calcium chewable tablet and production method thereof are mentioned. There are 1000 gr of calcium carbonate, 0.2 - 0.3 gr of vitamin D₃, 225 to 235 gr of milk powder, 190 to 210 gr of sorbitol, 30 to 40 gr of dextrin and 30 to 40 gr of starch in the vitamin C calcium chewable tablet comprising vitamin D in the said document. The amount of vitamin D₃ by weight is quite low in the chewable tablet mentioned in the said document. In another patent document of WO 2016086557 in the state of the art, a chewable tablet with the composition of calcium carbonate vitamin D and preparation method thereof are mentioned. In the said document, it is mentioned that this tablet comprises starch, sucrose and pure water beside calcium carbonate and vitamin D. Vitamin D₃ is not the only active agent and its amount in the tablet is quite low in the document.

In another patent document of US 20160089383 in the state of the art, a food supplement is mentioned. It is stated that vitamin D is in the amount of 400 IU to 10,000 IU in the said food supplement and the food supplement comprises 10 mg to 250 mg of genistein, 30 mg to 1000 mg of resveratrol, 40 mg to 1000 mg of quercetin in addition to vitamin D. It is mentioned in the document that the food supplement is in the forms of capsule, tablet, dragee, powder, chewable like gum or granule. However, a pharmaceutical form comprising only vitamin D₃ is not given in the document.

In another patent document of CN 103494836 in the state of the art, a composite chewable tablet comprising calcium carbonate and vitamin D₃ for children and old people is mentioned. It is indicated in the document that the said tablet consists of calcium carbonate, vitamin D₃ and excipients. However, a pharmaceutical form comprising only vitamin D₃ is not given in the said document and the amount of vitamin D₃ is quite low. In the prior art documents given above, vitamin D₃ is not the only active agent in the pharmaceutical forms comprising vitamin D₃. In case that a single vitamin source comprising necessary doses is not used, patients have to meet said their vitamin needs from one or more specific-vitamin sources. This causes additional medicine consumption and decreasing adaptation to the vitamin regime. Therefore; patients cannot take the vitamin in the dose for which their bodies need and in one go. Thus, developing a pharmaceutical form which is easy to use and which especially comprises vitamin D₃ in high amounts is needed. Therefore; all or significant amount of vitamin D₃ for which the body needs may be taken when the pharmaceutical compound is used in one go. In addition, it is important that there are easy to use medicine forms when patients' usage is considered. Therefore; developing forms for this is required. Thus, a pharmaceutical form which is chewable and comprises high amount of vitamin D₃ in a unit tablet has not been developed in the state of the art.

Brief Description of the Invention:

The aim of the invention is to carry out an easy to use pharmaceutical product which provides that the active agent cholecalciferol is taken in high dose to meet the need for vitamin D₃.

In the pharmaceutical product developed for this aim, doses of cholecalciferol change in the range of 600 IU and 3000 IU. In addition, the pharmaceutical product developed is in chewable tablet form. The most important advantage of chewable tablets is being easy to use due to the fact that patients do not have to keep water with them. Therefore; chewable tablet forms provide higher patient comfort than other tablet forms.

Detailed Description of the Invention:

The disclosed pharmaceutical product comprises an active agent cholecalciferol as a vitamin D₃ source and at least one excipient. In an embodiment of the invention, the pharmaceutical product comprises cholecalciferol in the range of 600 IU and 3000 IU in a unit tablet.

• The product obtained from the disclosed pharmaceutical formulation is in a pharmaceutical product form which user can use quite easily. The pharmaceutical product is in tablet form in the preferred embodiment of the invention. The preferred form is chewable tablet in this embodiment.

The amount of the active agent cholecalciferol in the said product is in the range of 600 IU and 3000 IU in a unit tablet in an embodiment of the invention. In another embodiment of the invention, the amount of cholecalciferol is inthe range of 1000 IU and 3000 IU in a unit tablet. In another preferred embodiment of the invention, the amount of cholecalciferol is 1000 IU in a unit tablet.

In the preparation of chewable tablet from the disclosed formulation, various excipients are used. Diluents (mannitol), binders (povidone), flavorants (mint flavor), lubricants (magnesium stearate), artificial sweeteners (saccharin sodium) and glidants (colloidal silica) may be counted among excipients that may be used but not limited to these.

The formulation comprises 50 mg to 1000 mg of mannitol by weight as the diluent, 5 mg to 50 mg of povidone by weight as the binder, 0,1 mg to 15 mg of colloidal silica by weight as the glidant, 0,15 mg to 1,0 mg of saccharin sodium by weight as the artificial sweetener, 0,9 mg to 25 mg of flavor preferably mint flavor by weight as the flavorant, 10 mg to 100 mg of magnesium stearate by weight as the lubricant. This amount ranges of the excipients given in the invention are for the formulations comprising cholecalciferol in equivalent amount to 600 IU to 3000 IU.

The disclosed cholecalciferol chewable tablet is prepared by using direct compression method in its production. The examples related to the formulations in which the invention is applied are below. The invention is not limited to this examples. The amounts of the excipients which may be used in case that cholecalciferol is in doses that are equivalent to 600 IU, 1000 IU, 2000 IU and 3000 IU are given by weight in the example tables below.

Example 1;

Example2: Unit Formula of Cholecalciferol 1000 IU Chewable Tablet

Weight amount in the unit

Ingredients Intended use formula (mg/ ITablet)

Cholecalciferol

equivalent amount to 1000 IU Active agent (Premix)

Mannitol 100 SD 270,35 Diluent

Povidone K-30 6,00 Binder

Aerosil 1,50 Glidant

Saccharin Sodium 0,15 Sweetener (Artificial)

Mint Flavor 0,90 Flavor

Magnesium Stearate 12,00 Lubricant

Example 3:

Example 4:

The invention is not limited with the embodiments disclosed above and a skilled person in the art can perform different embodiments of the invention easily. They should be evaluated within the scope of the invention protection demanded with claims.

Claims

1. A pharmaceutical formulation in chewable tablet form comprising an active agent cholecalciferol as a vitamin D₃ source and at least one excipient;

characterized by comprising the active ingredient cholecalciferol in the amount of 600 IU to 3000 IU in a unit tablet.

2. The pharmaceutical formulation in chewable tablet form according to claim 1 characterized by comprising the active agent cholecalciferol in the amount of 1000 IU in the unit tablet.

3. The pharmaceutical formulation in chewable tablet form according to claim 2 characterized by comprising excipients as follows; mannitol as a diluent, povidone as a binder, colloidal silica as a glidant, saccharin sodium as an artificial sweetener, mint flavor as a flavor, magnesium stearate as a lubricant.

4. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 50 mg to 1000 mg of mannitol by weight.

5. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 5 mg to 50 mg of povidone by weight.

6. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 0,1 mg to 15 mg of colloidal silica by weight.

7. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 0,15 to 1,0 mg of saccharin sodium by weight.

8. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 0,9 mg to 25 mg of flavor by weight.

9. The pharmaceutical formulation in chewable tablet form according to claim 3 characterized by comprising 10 mg to 100 mg of magnesium stearate by weight.

10. The pharmaceutical formulation in chewable tablet form according to any of claims above for use in the treatment of vitamin D₃ deficiency.