US3126321A

US3126321A - Table vii

Info

Publication number: US3126321A
Authority: US
Publication date: 1964-03-24
Anticipated expiration: 1981-03-24

Description

United States Patent Ofi 3,126,321 Patented Mar. 24, 1964 ice 3,126,321 SOFT GELATIN CAPSULES Walter M. Kurtz, Kalamazoo, Mich., assignor to The Upjohn Company, Kalamazoo, Mich, a corporation of Delaware No Drawing. Filed Jan. 26, 1962, Ser. N 169,093 4 Claims. (Cl. 167-83) This invention relates to gelatin capsules and more particularly to soft gelatin capsules enclosing oleaginous compositions.

Soft gelatin capsules are known in the art. They are usually composed of gelatin, water, and a plasticizer, such as glycerin, and can be formed into various shapes and sizes.

The soft gelatin capsule of commerce is usually in the form of a continuous outer shell of the composed gelatin enclosing a fluid or semi-fluid fill. Dissolution of the shell or expression of the enclosed fill therefrom frees the fill for its intended use.

Since water has a marked aifinity for gelatin and can exert thereby a deleterious action on the capsule shell, fills of an oleaginous type have been utilized to reduce the content of water in the fill. Even in the case of oleaginous-type fills, small amounts of water have caused defects in the yield and quality of capsules during preparation and storage. Similarly, defects have been encoun tered in capsules enclosing otherwise acceptable and useful oleaginous fills, for example, those including salts of strong acids and bases, such as sodium chloride; hygroscopic compounds, such as chloral hydrate; hydrochlorides, such as (o-methoxy-a-methylphenyl)-hydrazine hydrochloride; water soluble compounds, such as choline chloride; volatile solvents, such as alcohol; and non-volatile solvents, such as glycerin. The said defects greatly reduce the yield of quality-controlled capsules and impair the storage stability of the capsules; for example, through leaking, indenting, and shrinking of the capsules and the existence of excessively soft capsules and those with soft spots. Apparently, substances, such as the salts, hygroscopic compounds, hydrochlorides, water-soluble compounds, volatile and nonvolatile solvents, per so, have a deleterious action on the gelatin shell of the capsules, especially in the presence of water. The deleterious action of like substances is determined readily by a test run such as demonstrated in Tables I through VI.

It has now been discovered that, according to the present invention, oleaginous vehicles can be successfully filled into soft gelatin capsules by the use in the fill of an ingestible cellulosic compound, such as purified cellulose. The operability of an ingestible cellulosic compound is determined readily by a test run such as demonstrated in Example 1. As is known in the art, the oleaginous vehicles comprise fixed oils, such as corn oil and cottonseed oil; oily esters, such as isopropyl myristate; and the like. Oil-dispersible components, such as aluminum monostean ate, white wax, and hydrogenated oils, can be incorporated into the oleaginous vehicles. For oral administration the vehicles and any added components must be ingestible. The invention is especially advantageous in the case of an oleaginous fill including an ingredient having a deleterious action on the gelatin, and especially an ingredient having such action in the presence of Water.

The fill should be fluid enough for handling in the practical methods used in encapsulating flowing vehicles and compositions. An amount of the cellulosic compound up to about 20% by weight of the fill is feasible, and in some compositions higher amounts can be used. To provide best results any water included within the fill should usually be no more than about twice the amount of the cellulosic compound.

The mechanism of action of the said cellulosic compound in preventing the defects in yield and storage of the capsules is not completely understood. However, experimental data show that unexpectedly high yields of quality-controlled capsules are obtained from the compositions and process of the instant invention.

The heretofore unsolved problems are illustrated in the following tables, the percents of capsules accepted being those obtained after washing, drying and quality inspecting the capsules prepared by the known methods, the percents of ingredients being by weight.

TABLE I Results of Quality Control Inspection. Percent of Capsules Accepted oleaginous Vehicle 67.79, Balance- Corn Oil, Water, 15%

collapsed shells.

TABLE II Corn Oil, 84%; Compound A 16% 27.08, Balance- Leakers.

TABLE III 0.00, All leakers.

82.37, Balanceleakers.

0.00, All lcakers.

TABLE IV Corn Oil, alcohol, 10% 37.50, Balanceakers.

TABLE V Corn Oil, 90%; glycerol, 10%. 0.00, All spotted. Corn 011, 88%; glycerol, 12% 0.00, All spotted.

TABLE VI 90.22, Balance- Corn Oil, 93%; chloral hydrate, 7%

leakers.

Compound A is (o-methoxy-a-methylphenyl) hydrazine hydro chloride.

TABLE VII Results of Quality Oleaginous Vehicle Control Inspection,

Percent of Gapsules Accepted Corn Oil, 83%; purified cellulose, 6%; water, 117... 92.07.

TABLE VIII Coin gil, 89.1%; purified cellulose, 2%; Compound 99.25.

x CtXnSO9i l 86.1%; purified cellulose, 5%; Compound 99.76. Corii 91.1%; purified cellulose, Compound 99.08. Isopro pyi myristate, 84%; purified cellulose, 10%; 99.84.

Compound A, 16%. Corn Oil, 74%; crystalline cellulose, 10%; Com- 9936.

pound A, 16

TABLE IX Corn Oil, 83%; purified cellulose, 10%; NaGl, 7%... 96.60. Peamt Oil gel, 78%; purified cellulose, NaOl, 96.47.

1 Coru Oil, 77%; purified cellulose, 10%; NaCl, 3%; 97.30.

water, 10%.

TABLE X Corn Oil, 80%; purified cellulose, 10%; alcohol, 10%. 99.28.

TABLE XI (Joan Oil, 80%; purified cellulose, 10%; glycerin, 97.08, No soil;

1 spots. Corn Oil, 76%; purified cellulose, 12%; glycerin, 99.44, No spotting 12%. or shrinking.

TABLE XII Corn Oil, 74%; purified cellulose, 10%; chloral 07.84.

hydrate, 10%. Corn Oil, 81%; purified cellulose, 10%; chloral 95.67.

hydrate, 7%; water, 2%.

Compound A is (o-metlioxy-a-methylphenyl) hydrazine hydrochloride.

The above data show the superiority, greatly improved yields and acceptable physical characteristics of the capsules and methods of the instant invention.

In the manner and process of making the invention, an oleaginous composition is prepared by mixing and blending the components thereof into a homogeneous whole, using the known techniques for preparing oleaginous vehicles for encapsulation into soft gelatin capsules. The order of addition of components to the oleaginous vehicle is not critical. The oleaginous fill is thereafter encapsulated by the known techniques.

The invention is used to provide increased yields of accepted soft gelatin capsules, especially ingestible soft gelatin capsules.

The following examples set forth the best mode contemplated by the inventor of carrying out his invention.

EXAMPLE 1 Capsules Enclosing an Oleaginous Composition Comprising Water 400 cms. of an oleaginous composition is prepared from the following ingredients:

Grams Purified water, U.S.P 60 Corn oil 300 Purified cellulose, powdered 40 4i The composition is encapsulated into 2.65 minim soft gelatin capsules by the known techniques. 99.6 percent of the capsules are found acceptable by the quality control inspectors.

EXAMPLE 2 Capsules Enclosing an Oleaginous Composition Comprising a Hydrochloride 300 gms. of an oleaginous composition is prepared from the following ingredients:

Grams (o Methoxy-a-methylphenyl)hydrazine hydrochloride 48 Isopropyl myristate 222 Purified cellulose 30 EXAMPLE 3 Capsules Enclosing an Oleaginous Composition Comprising a Volatile Solvent 400 gms. of an oleaginous composition is prepared from the following ingredients:

Grams Alcohol, U.S.P 40 Corn oil 320 Purified cellulose 40 Capsules Enclosing an Oleaginous Composition Comprising a Nonvolatile Solvent 400 gms. of an oleaginous composition is prepared from the following ingredients:

Grams Glycerin, U.S.P 40 Cottonseed oil 320 Purified cellulose 40 300 gms. of an oleaginous composition is prepared from the following ingredients:

Grams Chloral hydrate 48 Corn oil 222 Purified cellulose 30 The corn oil is stirred vigorously, and the chloral hydrate is added gradually to form a good solution. Thereafter the purified cellulose is added during continuous stirring to form a homogeneous mixture.

The composition is encapsulated into 2.65 minim soft gelatin capsules by the known techniques. 97.84 percent of the capsules are found acceptable by the quality control inspectors.

EXAMPLE 6 Capsules Enclosing an Oleaginous Composition Comprising a Salt and Water 400 gms. of an oleaginous composition is prepared from the following ingredients:

Grams Sodium chloride, powder l2 Purified water, U.S.P 40 Corn oil 308 Purified cellulose 40 of the capsules are found acceptable by the quality control inspectors.

What is claimed is:

1. A filled soft gelatin capsule wherein the fill comprises a fluid oleaginous vehicle and powdered ingestible cellulose.

2. A filled soft gelatin capsule wherein the fill comprises a fluid oleaginous vehicle, powdered ingestible cellulose, and an ingredient having a deleterious action on gelatin.

3. A filled soft gelatin capsule wherein the fill comprises a fluid oleaginous vehicle and up to about 20% by weight of the fill of powdered ingestible cellulose.

4. A filled soft gelatin capsule wherein the fill comprises a fiuid oleaginous vehicle, up to about 20% by weight of the fill of powdered ingestible cellulose and an ingredient having a deleterious action on gelatin.

References Cited in the file of this patent UNITED STATES PATENTS Murphy Oct. 24, 1950 2,581,038 Middendorf Jan. 1, 1952 2,667,268 Grifiin Jan. 26, 1954 2,780,355 Palermo et al Feb. 5, 1957 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,126,321 March 24', 1964 Walter M Kurtz It is hereby certified that error appears in the above numbered pat- I ent req'iiring correction and that the said Letters Patent should read as corrected below.

Column 3, TABLE VIII, line 7 thereof, for "84%" read 74% same column 3, line 64, for "400 cms, read 400 Gms.

Signed and sealed this 28th day of July 1964a (SEAL) Attest:

EDWARD J. BRENNER Commissioner of Patents ESTON G. JOHNSON Attesting Officer