VITAMIN COMPOSITION WITH ENHANCED BIOAVAILABILITY AND METHOD OF ADMINISTERING SAME

Abstract: A vitamin or mineral composition with enhanced bioavailability is disclosed including at least one vitamin or mineral, a polyoxyethylene sorbitan ester, and a diluent, such as polyols or vegetable oils.

Description: VITAMIN OR MINERAL COMPOSITION WITH ENHANCED BIOAVAILABILITY AND METHOD OF ADMINISTERING SAME The present invention relates to vitamin and mineral compositions, particularly vitamin and mineral compositions in a solid unit dosage form. Vitamins are a group of substances of diverse chemical composition. They are in general inorganic and organic substances that must be provided in small quantities in the diet for the synthesis by tissues, of cofactors that are essential for various metabolic reactions. As is well known, vitamin deficiency may be due to improper or inadequate diet or may be caused by a variety of disease conditions. Examples are diseases of the liver and bilary tract, prolonged diarrhoea from any cause, hyperthyroidism, anemia together with a variety of other disorders of the digestive system, including those related to alcoholism. There are therefore available numerous vitamin tablets, capsules and injections to aid in the treatment of such vitamin deficiencies. The effectiveness of the intake of such vitamin compositions is dependent, inter alia, upon the level of bioavailability of these vitamins in the patient's system. Bioavailability is defined as the rate and extent of uptake (absorption) by an animal or human of a chemical substance -either natural or synthetic. Bioavailability may be expressed in percentage terms over a predetermined time versus concentration of drug substance or vitamin in blood plasma. This is plotted as a curve and the area under the curve (AUC) is then measured and can be compared for several dosage forms to measure the bioavailability of a drug or vitamin. An increase in AUC thus indicates an increase in bioavailability. It would be desirable if the level of bioavailability could be increased as this may have the effect of increasing the effectiveness of the vitamin intake. This may also have the effect of reducing the dosages required. Accordingly, it is an object of the present invention to overcome, or at least alleviate, one or more of the deficiencies related to the prior art. Composition in accordance with the present invention provides a vitamin or mineral composition having enhanced bioavailability, and comprises (a) at least one water or oil soluble vitamin or mineral; and (b) at least one primary pharmaceutical adjunct. The vitamin composition may be in a solid unit dosage form. The solid unit- dosage form may be in the form of tablets, hard shell capsules and soft elastic capsules. Soft elastic capsules are preferred. Solf gelatin capsules are particularly preferred. While it is unclear as to the mechanism by which bioavailability is enhanced, it is postulated that the increase in bioavailability could be attributed to presenting the vitamins to the sites of absorption in the gastrointestinal tract in an optimal form. This may be extrapolated to all vitamins as the rate limiting step in absorption and hence bioavailability. The dissolution and presentation of the vitamins to the gastrointestinal tract in optimal physical form will vary. For oil soluble vitamins, microemulsium would appear to be the optimum physical form. For water soluble vitamins, solution would appear to be the optimum physical form. The vitamin composition according to the present invention may optionally include (c) at least one secondary pharmaceutical adjunct. The oil soluble vitamin component may be selected from vitamin A, D, E, K or a mixture thereof. The water soluble vitamin component may be selected from vitamin t B2, B6, B12 t C, niacinimide, pantothenic acid and the like or a mixture thereof. The preferred oil soluble vitamins are vitamins A and E. The vitamins may be utilized in any standard form. For example, vitamin A may be presented as Vitamin A palmitate. Vitamin D may be present as calciferol solution. Vitamin E may be present as d-alpha tocopherol. Vitamins B1 and B6 may be present as their hydrochloride derivatives. The preferred primary adjuncts may be selected from the polyoxyethylene sorbitan ester group, e.g., the sorbitan esters sold under the commercial names of Polysorbate 20 and Polysorbate 80. These compounds are listed in the British Pharmacopoeia and are safe for use in food and pharmaceuticals. Secondary pharmaceutical adjuncts which may desirably be included include nontoxic alcohols and other diluents such as vegetable oils and derivatives thereof. Useful nontoxic alcohols include polyols such as glycerol, sorbitol, propylene glycol and high molecular weight polyol block polymers. Modified vegetable oils such as acetylated monoglyceride may also be used. The water or oil soluble vitamins may be present in the vitamin composition in any suitable amounts. A concentration of between approximately 10 and 80 weight percent based on the weight of the total vitamin composition may be used. The vitamin compositions may include a single vitamin component, for example, the oil soluble vitamins when used alone may be compounded with a polyoxyethylene sorbitan ester, e.g., Polysorbate 80, together with an alcohol such as ethanol and glycerol. A further sorbitan ester such as sorbitan monoleate may also be included. For such oil soluble compositions, the amount of vitamin used may vary from approximately 15 to 60% by weight. The polyoxyethylene sorbitan ester component is desirably present in relatively high quantities for example from approximately 35 to 75% by weight. The vitamin composition according to the present invention may be of the multivitamin or multivitamin/mineral type. For example, the vitamin composition may include vitamins A, D, E, B1, B2, B6, B1z, C, niacinimide and pantothenate in a single solid unit dosage form. The amounts of individual vitamins may vary depending on the estimated safe and adequate daily dietary intakes of particular vitamins. For such multivitamin compositions, a relatively high amount of polyoxyethylene sorbitan ester, e.g., Polysorbate 80, of approximately 50 to 80% has been found to be effective. As stated above, the vitamin compositions may be prepared in any suitable solid unit dosage form. The increase in vioavailability has been found to be particularly effective with a solid unit dosage form of a soft elastic gelatin capsule. Such a capsule may be manufactured from gelatin, glycerin and optionally sorbitol. The preferred primary adjuncts may desirably be liquids or soft waxes since soft elastic gelatin capsules are for encapsulation of liquids to convert them to a solid unit form. The following examples illustrate vitamin composition formulae according to the present invention. The primary and secondary pharmaceutical adjuncts are compounded with vitamins and encapsulated into soft elastic gelatin capsules. Example 1 Ingredients Fill amount per cap Vitamin E (as d-alpha Tocopherol) 500 mg. Polysorbate 80 300 mg. Ethanol 50 mg. Glycerol 30 mg. The bioavailability of vitamin E in the above-mentioned composition was measured and compared to conventional solid dosage forms. The bioavailability was demonstrated to have increased by approximately 27% in humans. Example 2 Ingredients Fill amount per cap Vitamin A (as Vitamin A Palmitate 50 mg. 1 x 106 i.u./gram) Polysorbate 80 200 mg. Glycerol 20 mg. Sorbitan Monoleate 10 mg. The bioavailability of vitamin A in the above-mentioned composition was measured and compared with the bioavailability in conventional solid dosage forms. The bioavailability was demonstrated to have increased by approximately 60% in humans. Example 3 Ingredients Fill amount per cap Vitamin A (as Vitamin A Palmitate 1 x 106 i.u./gram) 5.0 mg. Vitamin D (as Calciferol Solution 2 x 106 i.u./gram) 0.2 mg. Vitamin E (as d-alpha Tocopherol) 50.0 mg. Vitamin B1 (Thiamine CURL) 10.0 mg. Vitamin B2 (Riboflavin) 10.0 mg. Vitamin B6 (Pyridoxine HCL) 10.0 mg. Vitamin B12 (Cyanocobolamin) 5.0 mg. Vitamin C (Ascorbic Acid) 200.0 mg. Niacinamide (Nicotinamide) 50.0 mg. Calcium Pantothenate 20.0 mg. Polysorbate 80 400.0 mg. Sorbitan Monoleate 20.0 mg.

Claims: CLAIMS: 1. A vitamin or mineral composition for incorporation into a solid unit dpsage form comprising a unit dosage amount of at least one vitamin or mineral and a polyoxyethylene sorbitan ester, said ester being present in an amount of about 30 percent to about 80 percent based on the total weight of said composition-. 2. A composition as claimed in Claim 1 including a diluent of an alcohol, a vegetable oil and derivatives or a vegetable oil. 3. A composition as claimed in Claim 1 or 2 including a plurality of vitamins, said ester being present in an amount of about 50 percent to about 80 percent based on the total weight of said composition. 4. A composition as claimed in Claim 1 including an oil soluble vitamin A, vitamin D, vitamin E, and/or vitamin K. 5. A composition as claimed in Claim 1 including a water soluble vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, niacinimide, and/or pantothenic acid. 6. A composition as claimed in Claim 2 wherein said diluent is a polyol, glycerol, sorbitol, propylene glycol a high molecular weight polyol block polymers or a modified vegetable oil. 7. A composition as claimed in Claim 6 wherein said modified vegetable oil is acetylated monoglyceride. 8. A composition as claimed in any of the preceding claims wherein said ester is present in an amount of from about 35 percent to about 75 percent based on the total weight of said composition. 9. A method of administering at least one vitamin of mineral to a warm-blooded mammel comprising the following steps: (a) preparing a composition as claimed in any of the preceding claims; and (b) orally administering the composition to the warm-blooded mammel. 10. A method as claimed in Claim 9 wherein said composition is incorporated into a tablet, a hard shell capsule or a soft elastic capsule.

Inventors: BATEMAN, NEIL E.
Applicants: R.P. SCHERER CORPORATION
Application year: 1984
Main classification: A61K47
IPC codes: A61K9, A61K45, A61K31, A61P3, A61K47