WO2002091852A1

WO2002091852A1 - Oral delivery system and method for making same

Info

Publication number: WO2002091852A1
Application number: PCT/US2001/040723
Authority: WO
Inventors: John T. Cooker
Original assignee: Cooker John T
Priority date: 2001-05-14
Filing date: 2001-05-14
Publication date: 2002-11-21

Abstract

The present invention is directed to improved oral dosage forms that are significantly easier to swallow. In accordance with the present invention, the oral dosage forms are configured to have relatively greater weight and/or density to effect partial or total submergence in the liquid with which the oral dosage form is taken. In one embodiment, a filler is added to the ingredients of the oral dosage form. In another embodiment, a filler is added to the medium of the oral dosage form. In a further embodiment, a filler is added to the exterior of the oral dosage form. In another embodiment, a relatively heavier, denser or larger amount of ingredient is used to formulate the oral dosage form. In yet a further embodiment, a binder is used to increase the weight and/or density of the oral dosage form. In yet another embodiment, a combination comprising a binder and a relatively heavier, denser or larger amount of ingredient is used to formulate the oral dosage form. In accordance with the present invention, oral dosage forms are configured to have a predetermined weight and/or density while conforming its size to what can be comfortably swallowed.

Description

DESCRIPTION

ORAL DELIVERY SYSTEM AND METHOD FOR MAKING SAME

Technical Field

The present invention generally relates to an oral delivery system.

Background Art

Over the years, the pharmaceutical industry has developed a variety of

medications, medicaments, vitamins, nutritional supplements, etc. (collectively

referred to herein as "oral dosages") that can be taken orally and which are in the

form of capsules, tablets, gel caps and their like (collectively referred to herein as

"oral dosage forms"). However, many consumers have experienced difficulty in

swallowing such oral dosage forms. Specifically, many types of available oral

dosage forms become buoyant on the liquid with which they are taken. This is

especially the case with capsules which are hardened reservoirs of gelatin filled

with powdered ingredients and air. As a result of such a configuration, the

powdered ingredients and air become bubbles sealed in gelatin.

The buoyancy of the oral dosage forms on the liquid causes discomfort and

creates difficulty in swallowing. Specifically, the buoyancy property creates the

following problems:

1) the buoyancy of the oral dosage form works against the downward

motion of swallowing and also reduces control of the oral dosage form

by the tongue and pharynx muscles;

2) the dry gelatin outer surface of a capsule or gel cap, when wetted,

quickly becomes sticky and easily adheres to surfaces it contacts. As a result, the oral dosage forever may be left behind as it follows the liquid

down the pharynx and esophagus thereby requiring successive swallows

of additional liquid to flush down the oral dosage form; and

3) a capsule, while floating on the liquid, may move out of its intended

aligned position in which the narrow end of its cylindrical shape points

toward the pharynx and esophagus and as a result, is swallowed at an

uncomfortable angle, possibly becoming lodged in the process.

Oral dosage forms that have a cylindrical, oval or rectangular shape (but not

round), and are not heavy enough to sink on the liquid with which they are taken

may move out of their aligned position while being propelled by the tongue

toward the pharynx and esophagus thereby being swallowed at an uncomfortable

angle.

The pharmaceutical industry has attempted to solve these problems by

developing various oral dosage forms that supposedly have improved

swallowabilty. In their attempt to solve the aforementioned problem relating to

swallowability, the pharmaceutical industry has focused on the size, shape and

surface composition of the capsules, tablets, gel caps, etc. In another attempt to

address the problem of swallowability, the industry developed and produced

cylindrical-shaped tablets which were to replace round shaped tablets, (i.e. a

capsule shaped tablet). One result of the pharmaceutical industry's attention to this

problem was the development of the gelatin-coated caplet which not only

addressed the problems relating to swallowability but also consumers' wariness of

capsule tampering. Such a caplet is disclosed in U.S. Patent No. 5,314,537. Although the gelatin-coated caplet has provided improvement in the

swallowability of such caplets, the pharmaceutical industry's attempts to solve this

problem are basically limited to the application of coatings to the exterior of the

caplet, tablet, etc.

Despite the improvements discussed above, consumers still continue to express

desire for oral dosage forms that exhibit improved swallowability characteristics.

It is therefore an object of the present invention to provide new and improved

oral dosage forms that solve the problems discussed above.

Still other objects and advantages of the present invention will in part be

obvious and will in part be apparent from the specification.

Disclosure of the Invention

The present invention is directed to improved oral dosage forms that are

significantly easier to swallow. In accordance with the present invention, the oral

dosage forms are configured to have relatively greater weight and/or density to

effect partial or total submergence in the liquid with which the oral dosage form is

taken.

In one embodiment, the present invention is directed to an oral dosage form for

ingestion with liquid, comprising, an active ingredient, an inactive ingredient, and

a substance having a predetermined weight that effects at least partial sinking of

the oral dosage form in the liquid.

In one embodiment, the substance is a filler that is added to the active and

inactive ingredients of the oral dosage form. In another embodiment, a filler is added to the medium of the oral dosage form.

In a further embodiment, a filler is added to the exterior of the oral dosage

form.

In another embodiment, a relatively heavier, denser or larger amount of active

and inactive ingredients are used to formulate the oral dosage form.

In yet a further embodiment, the substance is a binder that is used to increase

the weight and/or density of the oral dosage form.

In yet another embodiment, a combination comprising a binder and a relatively

heavier, denser or larger amount of ingredient is used to formulate the oral dosage

form.

In accordance with the present invention, oral dosages are configured to have a

predetermined weight and/or density while conforming its size to what can be

comfortably swallowed.

Oral dosage forms have a variety of physical characteristics, such as the

medium used for transport. Thus, the present invention teaches a variety of

configurations of oral dosage forms and methods for making these oral dosage

forms, that solve the aforementioned problems and deficiencies associated with

conventional oral dosage forms.

The configurations and methods of the present invention are applicable to the

three major types of oral dosage forms: (1) capsules, (2) tablets and caplets, and

(3) soft-gels. Brief Description of the Drawings

The features of the invention are believed to be novel. The figures are for

illustration purposes only and are not drawn to scale. The invention itself,

however, both as to organization and method of operation, may best be understood

by reference to the detailed description which follows taken in conjunction with

the accompanying drawings in which:

FIG. 1 is a perspective view of one embodiment of a capsule configured in

accordance with the present invention wherein a filler is added to the capsule.

FIG. 2 is a perspective view of a capsule having thereon indicia to indicate the

portion of the capsule having concentrated weight.

FIG. 3 is a perspective view of a further embodiment of a capsule configured in

accordance with the present invention wherein filler granules are added to the

capsule.

FIG. 4 is a perspective view of yet a further embodiment of a capsule

configured in accordance with the present invention wherein a single filler

substance is added to the capsule.

FIG. 5 is a perspective view of yet another embodiment of a capsule configured

in accordance with the present invention wherein a filler substance is attached or

adhered to the exterior of the capsule.

FIG. 6 is a perspective view of yet a further embodiment of a capsule

configured in accordance with the present invention wherein the filler is molded

into one of the capsule portions. FIG. 7 is top plan view, partially in cross-section, of one embodiment of a

tablet configured in accordance with the present invention wherein a tablet is

embedded in one portion of the filler.

FIG. 8 is a top plan view, partially in cross-section, of one embodiment of a

softgel configured in accordance with the present invention wherein a filler is

embedded in one portion of the softgel.

FIG. 9 is a perspective view of a conical-shaped tablet configured in

accordance with the present invention wherein a filler is dispersed throughout the

tablet.

FIG. 10 is a top plan view of a generally trapezoidal-shaped tablet having filler

dispersed throughout the tablet.

Modes For Carrying Out The Invention

In describing the preferred embodiments of the present invention, reference

will be made herein to Figs. 1-10 of the drawings in which like numerals refer to

like features of the invention.

It has been found that by increasing the weight of oral dosage forms,

unexpected superior results are achieved in that the swallowability of the oral

dosage forms is significantly improved. In particular, it has been found that an

oral dosage form configured to have a relatively greater weight than that of a

conventional, but same type, oral dosage form, has significantly improved

swallowability characteristics. Specifically, the "weighted" oral dosage form

results in a significantly greater gravitational force being exerted upon the oral dosage form which facilitates direct and relatively quicker passage of the oral

dosage form through the pharynx and into the stomach.

It has also been found that increasing the density of oral dosage forms,

unexpected superior results are achieved in that the swallowability of the oral

oral dosage form configured to have a relatively greater density than that of a

conventional, but same type, oral dosage form has significantly improved

swallowability characteristics. Specifically, the oral dosage form having the

greater density has significantly less buoyancy with respect to the liquid which is

taken with the oral dosage form. (As described in the foregoing discussion, it is

buoyancy that resists the swallowing process). Thus, by significantly reducing

buoyancy of the oral dosage form, the swallowability of the oral dosage form is

greatly enhanced.

It also has been found that increased weight and/or density concentrated at a

particular end or side of an oral dosage form maintains the oral dosage form in a

preferred and intended alignment by vertically positioning oral dosage form as it is

swallowed. The heavier end is positioned such that it points generally in the

direction of the pharynx and the lighter end points generally toward the mouth.

As a result, swallowability is significantly enhanced because the probability of the

oral dosage form being swallowed at an uncomfortable angle is significantly

reduced.

In a preferred embodiment, the increased weight and/or density concentrated at

a particular end or side of an oral dosage form is such as to cause the oral dosage form to sink entirely in the liquid which is taken with the oral dosage form while

maintaining the vertical alignment of the oral dosage form as discussed above. In

an alternate embodiment, the increased weight and/or density concentrated at a

particular end or side of an oral dosage form is such as to cause the oral dosage

form to partially sink in the liquid while maintaining the vertical alignment of the

oral dosage form as discussed above.

As described above, in one embodiment of the present invention, a filler is

added to the ingredients of the oral dosage form. The filler may be in solid, semi-

solid, liquid or powder form. Furthermore, the filler may be inactive or may

provide an active function, e.g. digestive aid. The filler can be formulated out of

any commercially available soluble or insoluble filler including sucrose, dextrose,

lactose, fructose, microcrystaline cellulose, calcium carbonate, sorbitol, xylitol,

isomalt, gelatin, and starches. However, it is to be understood that other types of

commercially available fillers can be used as well. The filler can be added at any

convenient time during the filling process. In one embodiment, the filler material

is comprised of solid sucrose granules which are added to the ingredients of an

oral dosage form. In another embodiment, a solid sucrose portion is molded or

adhered to the inside of an oral dosage form. In a further embodiment, the filler is

applied as a relatively thick shell of sorbitol to the oral dosage form.

In accordance with the present invention, the filler is at one end of the oral

dosage form. In another embodiment, the filler is concentrated at the opposite end

of the oral dosage form. In such configurations, the end of the oral dosage form

having the filler is relatively heavier than the other end thereby causing the weighted end to sink first in the liquid taken with the oral dosage form. The oral

dosage form becomes vertically positioned due to the weighted end sinking first.

In a preferred embodiment, the oral dosage form having a weighted end includes

indicia to indicate which end of the oral dosage form is weighted. In the case of

capsules, the indicia enables consumers to align the heavier end first in their

mouth so as to use the capsule's cylindrical shape to facilitate correct alignment of

the capsule and movement of the capsule through the throat and into the

esophagus. The indicia on the weighted end decreases the chance of the oral

dosage form becoming swallowed at an angle that causes discomfort. As a result,

confidence is instilled in the consumer when using the oral dosage form. In one

embodiment, the indicia on the weighted end of the oral dosage form is a

predetermined color.

In another embodiment, the oral dosage form may be configured such that the

filler is part of the medium, e.g. capsule, or formed to the medium. In such a

configuration, a coating comprising the filler is disposed on the exterior surface of

the medium of the oral dosage form. In a preferred embodiment, the thickness of

the filler coating is between about 20 and 200 mils, inclusive. The filler coating

may be irregular in shape. The filler coating may be adhered to the medium of the

oral dosage form in many ways, e.g. coating, dipping, etc.

In a further embodiment, a relatively heavier or denser diluent is used as an

ingredient of the oral dosage form. In particular, a portion of a powdered diluent

used to bulk the volume of a capsule containing a small dosage of ingredients is

replaced with solid granules in order to increase the weight and/or density. In one example, rice flour in solid granule form is used. Rice flour in solid granule form

has a relatively greater density or weight and as a result, can be used in the same

available oral dosage form volume thereby effecting a relatively heavier and

denser oral dosage form.

In another embodiment, a binder is used to effect a relatively denser oral

dosage form. Conventional capsules are typically filled with free flowing

ingredients in powder form. However, conventional capsules do not use binders to

adhere the free flowing ingredients. In accordance with the present invention, a

binder is mixed with a portion of a capsule's ingredients in order to effect a

significant increase in the density of the end product. In one embodiment, a starch

binder is mixed with a portion of ingredients to form solids or semi-solids which,

when dried and combined with the remaining ingredients, form a relatively denser

end product. As a result, a smaller capsule can be used, or a relatively larger

amount of ingredients can be used in the original capsule. This process of binding

a portion of the ingredients of a capsule requires relatively less effort than

producing a complete tablet of all the ingredients and the end product still retains

the characteristics of a capsule, e.g. the capsules shiny, smooth surface.

In another embodiment, relatively large amounts of diluent and binder are

combined to form a composition that is used to formulate a tablet in order to

increase the weight and/or density of the tablet. In another embodiment, a binder

and a portion of an active ingredient or diluent of a capsule are mixed to form a

solid which when dried, is added to the other portions of capsule ingredients

thereby eliminating the need for a filler. It is to be understood that any of the aforementioned methods and techniques of

the present invention may be used in any combination to increase the weight

and/or density of an oral dosage form.

The ensuing description uses particular abbreviations for units of measure. To^"

facilitate understanding of the ensuing description, the following key of

abbreviations is provided:

Unit of Measure Abbreviation

liters 1

milliliters ml

grams g milligrams mg

Density D

It is to be understood that for purposes of facilitating understanding of the

present invention, the ensuing description is in terms of the liquid with which the

oral dosage form is taken as being water. However, it is to be understood that

other liquids may be used, e.g. soda, juice, coffee, etc. and that the weight and/or

density of the oral dosage form may have to be increased in accordance with the

present invention to eliminate buoyancy of the oral dosage form on those types of

liquids.

The ensuing description described inactive ingredients (e.g. excipients) which

are used in the production of oral dosages. Excipients are generally described in

U.S. Patent No. 5,725,884, the disclosure of which is incorporated herein by

reference. In order to facilitate understanding of the present invention, the ensuing

description is divided into separate discussions of each of the three types of oral

dosage forms: (1) capsules, (2) tablets and caplets, and (3) soft-gels.

1) Capsules

As discussed above, conventional capsules, in effect are sealed powder and air.

As mentioned in the foregoing discussion, the sealed powder and air have buoyant

characteristics. In accordance with the present invention, a capsule is provided

that is configured to sink in the liquid that is taken with the capsule. It has been

found that sinking of the capsule in the liquid effects a significant improvement in

the swallowability of the capsule without compromising other characteristics

consumers find favorable, i.e. shiny, smooth surface. In accordance with the

present invention, capsules are configured to have a relatively greater weight

and/or density than water (the density of water is 1 g/ml @ 4° Celsius) without

increasing the size of the capsule beyond consumer preference.

Example 1

A typical conventional capsule of 50 mg of the popular nutritional supplement

zinc contains excipients that weigh 462 mg. Its total weight is 512 mg in a size 0

capsule with a volume of 0.68 ml and has a density of: D = 0.512 g/0.68 ml or

0.75 g/ml. Since the density of this capsule is less than 1 g/ml, it will float on

water. In accordance with the present invention, the density D of the capsule is

increased to about 0.29 g/ml by the addition of a solid sucrose filler weighing 250

mg at 0.1 ml. As a result, the end product (i.e. the modified capsule) will weigh

762 mg at a volume of 0.73 ml. Due to compression in the filling process, the capsule will only expand 0.05 ml. Thus, the density-augmented capsule will now

have a density D that is equal to 0J62 g/0J3 ml, or 1.04 g/ml. The density-

augmented capsule will sink in the water with which it is swallowed thereby

overcoming the problems associated with capsule buoyancy discussed above.

Specifically, the density-augmented capsule will significantly reduce the

probability of the capsule moving out of correct alignment and being swallowed at

an angle. It is to be understood that the density of the density-augmented capsule

can be further augmented. However, in a preferred embodiment, the density

augmentation is such that it does not increase the size of the capsule beyond what

can be comfortably swallowed by consumers. However, it is to be understood that

in the case of a veterinary application, particular animals may be able to swallow

capsules having a size greater than the size preferred by consumers.

In Example 1 above, 250 mg or 32% of the total weight of the end product is

the result of the addition of the solid sucrose filler. Since the range of capsule

weight and density varies, the amount of the filler needed to achieve the objects of

the present invention also will vary. In a preferred embodiment, the percentage of

the total weight of the end product that is due to the addition of the filler ranges

between 15% and 80%, inclusive. More preferably, the percentage of the total

weight of the end product that is due to the addition of the filler ranges between

25% and 50%, inclusive, if the filler is used exclusively.

Example 2

In this example, the 512 mg weight of the above conventional capsule is

significantly increased at the same volume by the exchange of its powdered diluent for solid granules. Specifically, the 200 mg of a rice flour power diluent is

replaced by 400 mg of sucrose solid granules. The sucrose solid granules require

the same amount of space but weigh twice as much as the rice flour diluent. Thus,

the weight of the capsule is increased to 712 mg at the same volume with a density

D = 0J12 g/0.68 ml or 1.04 g/ml. Thus, the weight-augmented capsule will sink

in water.

Example 3

In this particular example, a binder is used to produce a capsule having a

relatively greater density. For this particular example, the conventional zinc

capsule as described above in Example 1, contains about 112 mg of powder zinc

and other excipients and about 400 mg of the rice flour diluent. In this example,

increasing the density of the capsule in accordance with the present invention

comprises the following steps: (a) subtracting 200 mg of the rice flour diluent, (b)

providing 200 mg of dry sorbitol, (c) mixing the sorbitol with liquid to form a

syrup-like binder, (d) mixing the syrup-like binder with the remaining 200 mg of

rice flour, (e) drying the mixture of the syrup-like binder and the rice flour, (f)

forming granules from the dried mixture, and (g) adding the granules to the 112

mg of powder zinc and remaining excipients. As a result, the total capsule weight

remains about the same but the volume of the capsule ingredients (zinc, excipients

and binder) shrinks or decreases 0.2 ml allowing the use of smaller capsule

portions. The density D of the end product would be 0.512 g/0.5 ml or 1.024

g/ml. This density is more than sufficient to allow the capsule to sink in water. If water is to be used as the liquid medium with which the capsule is taken,

then it is preferable that the density of the capsule be increased to at a density that

is greater than 1 g/ml so as to effect sinking of the capsule in the water. However,

it is to be understood that the density of the capsule, or any of the oral dosage

forms, can be increased in accordance with the present invention to effect sinking

of the oral dosage form in other types of liquids, e.g. soda, juices, coffee, milk,

etc.

In order to produce the oral dosage forms in accordance with the present

invention, particular, pertinent and novel manufacturing steps are implemented.

These steps are described in the ensuing description.

Capsules typically are comprised of two portions or components that are

pushed together to enclose the capsule ingredients. The capsule portions are

pushed together by applying a predetermined force. This type of "enclosing"

technique does not employ any type of steps to seal the capsule portions together

after the predetermined force is applied. However, it has been found that the force

currently being used in conventional processes to compress the ingredients to an

effective density is not sufficient because the capsule ingredients tend to bounce

back when the capsule portions are not sealed together. The method of the present

invention includes a particular step that pertains to the application of such force.

Specifically, the method of the present invention includes the step of applying a

relatively greater force to the capsule portions, in comparison to the force applied

in conventional capsule fabrication processes, in order to effect the extraction of

air from the powdered ingredients. The extraction of air from the interior of the capsule facilitates swallowability of the capsule. Furthermore, the increased force

facilitates the positioning of the filler and the ingredients within the capsule

volume.

In another embodiment of the method of the present invention, the capsule

portion holding the ingredients is configured to have a deeper well to

accommodate the filler material. This is illustrated in Fig. 1. Capsule 10

generally comprises portions 12 and 14. Portion 14 holds the ingredients during

the filling process. In one embodiment, portion 14 is configured to have a

relatively deeper "well" in order to accommodate filler material that is used to

increase the weight and/or density of the capsule in accordance with the present

invention. In such an embodiment, the length of portion 12 is increased to

accommodate filler material or binders (see FIG. 2). In another embodiment, the

length of portion 14 is increased to accommodate filler material or binders. In yet

a further embodiment, the diameter of portions 12 and 14 are increased to

accommodate larger amounts of filler materials or binders.

The filler may be configured to have any suitable shape. However, it has been

found that if a single solid filler is used in a capsule, then the preferred shape of

the filler should be generally spherical or oval in order to facilitate compacting

powder ingredients and filling air gaps. In one embodiment, the filler is covered

with a film material that prevents it from interacting with the ingredients.

In a further embodiment of the method of the present invention, the capsule

components, e.g. portions 12 and 14, are formulated to have a relatively greater

thickness to provide relatively greater strength to withstand the greater force resulting from addition of the filler. Furthermore, it is to be understood that the

added thickness of the capsule portions also contributes to the increase in weight

and density of the capsule in accordance with the present invention.

In another embodiment of the method of the present invention, a sealing

process is used to hold the joined capsule portions in place. Specifically, this

sealing process includes the step of applying an adhering agent around the seam of

the filled and joined capsule portions.

In a further embodiment, a locking process is used to hold the joined capsule

portions in place. In such a process, indentations or moldings are formed on the

capsule cap and body. The indentations or moldings are used to lock the cap and

body together. A plurality of indentations or moldings can be used to provide

capsules varying lengths.

In yet another embodiment of the method of the present invention, when the

weight of the capsule is increased to improve swallowability, as described above,

the weight is concentrated at one end of the capsule. When such a configuration is

used, indicia is applied to the weighted portion of the capsule. Such a

configuration is shown in Fig. 2. Capsule 20 comprises portions 22 and 24.

Portion 22 has indicia 26 to indicate that portion 22 is the weighted portion and

that capsule 20 should placed in the consumer's mouth so that weighted portion 22

is pointing toward the opening of the esophagus. In one embodiment, the indicia

comprises a color. However, it is to be understood that other types of indicia can

be used, e.g. letters, numbers, etc. Referring to Fig. 3, as described in the foregoing description, granules of a

particular substance, e.g. sucrose solid granules, are added to the capsule to

increase the weight and/or density of the capsule. Thus, the method of the present

invention includes the steps of (a) providing capsule 30 that comprises capsule

portions 32 and 34, (b) retaining portion 34 so that it is stationary, (c) depositing

ingredients 35 to portion 34, (d) depositing granules 36 into portion 34, and (e)

joining capsule portions 32 and 34 together. The method may also include the

step of applying indicia to the weighted portion of capsule 30 in a manner as

described above.

Referring to Fig. 4, the method of the present invention also provides particular

steps for using a single filler substance. Specifically, the method of the present

invention includes the steps of (a) providing capsule 40 that comprises capsule

portions 42 and 44, (b) retaining portion 44 so that it is stationary, (c) depositing

ingredients 45 to portion 44, (d) depositing single filler substance 46 into portion

44, and (e) joining capsule portions 42 and 44. The method may also include the

step of applying indicia to the weighted portion of capsule 40 in a manner as

described above.

Referring to Fig. 5, the method of the present invention also provides particular

steps for adding or attaching a filler substance to the exterior of either capsule

portion. Specifically, the method of the present invention includes the steps of (a)

providing capsule 60 that comprises capsule portions 62 and 64, (b) retaining

portion 64 so that it is stationary, (c) depositing ingredients 66 into portion 64, (d) adhering or attaching filler substance 68 to the exterior surface of portion 62, and

(e) joining capsule portions 62 and 64 together.

Referring to Fig. 6, the method of the present invention also provides particular

steps for molding a filler substance into either of the capsule portions.

Specifically, the method of the present invention includes the steps of (a)

providing capsule 80 that comprises capsule portions 82 and 84, (b) retaining

portion 84 so that it is stationary, (c) depositing ingredients 86 into portion 84, (d)

molding filler substance 88 into portion 82, and (e) joining capsule portions 82

and 84 together. In an alternate embodiment of this method, the filler substance

88 is adhered to the inside of either of the capsule portions

The method of the present invention also provides particular steps for adding a

filler substance to the capsule by forming one or both of the capsule portions with

the filler substance integral with the medium from which the capsule portions are

made.

The solid filler described above can be standardized in order to facilitate

automated manufacturing processes. The solid filler can be adhered to the inside

of the cap portion of the capsule while the cap portion is still empty. Capsules

typically are manufactured in standard sizes so that they may be handled by

automatic filling machines. Such standard sizes and respective volumes are

shown in Table I. Table I

Size 00 0 1

Volume 0.95 0.68 0.50 0.37 0.30 0.21 (ml)

In a preferred embodiment, the optimum size filler possible is adhered to the

cap portion of the capsule. As an example and for purposes of illustration, Table

II shows the filler weight needed to raise the powder ingredient density from 0J

g/ml to 1.0 g/ml for a given capsule size:

Table II

Size 00 0 1

Weight of

0.7 g/ml 665 476 350 259 210 147

Powder

Density

(mg)

Filler 285 204 150 111 90 63 Weight (mg)

2) Tablets and Caplets

In accordance with the present invention, tablets and caplets are produced with

relatively greater weight and density to improve swallowability of the tablets

and/or caplets. The increase in weight and density is accomplished by adding a

filler as described above. In one embodiment, the filler is added to the

ingredients. For example, in one embodiment, a solid sucrose filler is molded in

with the ingredients. In another example, the filler is embedded within the tablet

ingredients. In another embodiment, the filler is attached to the exterior of the tablet or

caplet. This example is illustrated in Fig. 7. Tablet 90 comprises portions 92 and

94. Portion 92 is comprised only of filler. Portion 94 is embedded within the

filler.

In yet another embodiment, the tablet is configured such that one side, end or

portion of the tablet has concentrated weight and has indicia to indicate which

side, end or portion has the concentrated weight.

In a further embodiment, increasing the weight and density of the tablet or

caplet is accomplished by increasing a component of the tablet or caplet. In one

embodiment, this is accomplished by increasing the weight of an excipient such as

the binder ingredient.

In a preferred embodiment, the percentage of the total weight of the end

product due to the addition of the filler or increase in the weight of the component

is between about 15% and 90%, inclusive. More preferably, the percentage of the

total weight of the end product due to the addition of the filler or increase in the

weight of the component is between about 25% and 15%, inclusive. For example,

50% of the weight of a 400 mg tablet augmented with 200 mg of filler is the result

of adding the filler. In this example, the original weight of the tablet has been

doubled or increased about 100%.

The increase in weight and/or density provides significantly improved

swallowability of particularly light, small sized tablets and caplets (i.e. under 300

mg, 4/10 ml). Referring to FIGS. 9 and 10, there are shown alternate embodiments of the

tablets and caplets of the present invention. These embodiments utilize a

particular shape having a swelled end which is substantially larger than the

opposite end. For example, FIG. 9 shows a conical-shaped tablet or caplet 200

which has swelled or enlarged end 202 and a relatively narrow end 204. Filler 206

is dispersed throughout tablet or caplet 200. Figure 10 shows a generally-

trapezoidal shaped tablet or caplet 208 which has a swelled or enlarged end 210

and a relatively narrow end 212. Similarly, filler 214 is dispersed throughout the

tablet or caplet 208. As a result of the shape of tablets or caplets 200 and 208,

swelled ends 202 and 210, respectively, are substantially heavier than the opposite

narrow ends. Thus, the swelled or enlarged ends sink in the liquid with which the

tablet or caplet is taken thereby effecting correct alignment of the tablet or caplet

and movement of the tablet or caplet through the throat and into the esophagus.

3) Softsels

In accordance with the present invention, the weight of softgels is increased to

improve swallowability thereof. In one embodiment of the present invention,

increasing the weight of softgels is effected by the addition of a filler.

Specifically, the filler is added to the ingredients, e.g. a solid sucrose portion.

This is illustrated in Fig. 8. Softgel 100 comprises portions 102 and 104. Portion

102 is comprised only of ingredients. Portion 104 includes filler 106. In one

embodiment, filler 106 is comprised of solid sucrose.

In another embodiment of the present invention, increasing the weight of

softgels is accomplished by increasing the amount of a component. For example, if the component is a liquid excipient, then the amount of the excipient is

increased. Increasing the amount of the component can also be realized by

increasing the size or thickness of the softgel.

In another embodiment, the softgels can be configured that one side or portion

of the softgel has concentrated weight and has indicia to indicate this end.

In a preferred embodiment, the percentage of total weight of the softgel that is

due to the addition of the filler or increase in component is between about 15%

and 90%, inclusive. More preferably, the percentage of total weight of the softgel

that is due to the addition of the filler or increase in component is between about

25% and 75%, inclusive.

The increase in weight and/or density provides significantly improved

swallowability of particularly light, small sized softgels (i.e. under 300 mg, 4/10

ml).

In an alternate embodiment of the present invention, filler is placed in the body

portion of the capsule along with the ingredients. The cap portion is then attached

to the body portion. In such a configuration, the size of the body portion is

increased so as to enable filler and ingredients to fit in the body portion.

In accordance with such an alternate embodiment, a solid filler of micro-

crystalline cellulose or lactose dropped into the body portion before the empty

capsules are shipped. Adhering agents are necessary. In order to achieve

maximum effect, a maximum weight and volume of filler should be used with a

given capsule size thereby creating a system of standardization of filler sizes and corresponding increased capsule sizes. The following example illustrates this

concept.

Example 4

A 0.500 ml size #1 capsule is typically used to fill 400 mg of ingredients. In

accordance with this embodiment of the present invention, the size of the capsule

is increased to a size #00 with a 0.950 ml capacity. The additional 0.450 ml of

volume is used for the filler. When a filler having a density of 1.5 g/ml is used,

the extra 0.450 ml volume would accommodate a filler weighing 675 mg. Thus,

standardization can be achieved for any size capsule.

In another embodiment of the present invention, a size #00 capsule is

configured to have an elongated geometry so as to provide a further 0.135 ml of

volume (or 14% increase in space) for a filler weighing 202 mg. As used herein,

the designation "el" refers to such elongated capsule geometry.

Table III shows typical commercially available capsule sizes and corresponding

capsule volumes.

Table III

Typical Capsule Size Capsule Volume (ml)

00 0.950

0 0.680

1 0.500

2 0.370

3 0.300

4 0.210

5 0.130

Table IV shows specific filler weights, filler volumes and corresponding

increased capsule sizes in accordance with the present invention.

Table IV

Powder Density (g/ml) Capsule Fill Weights (mg)

0.6 570 408 300 222 180 126 78

0.7 665 476 350 259 210 147 91

0.8 760 544 400 296 240 168 104

0.9 855 612 450 333 270 189 117

1.0 950 680 500 370 300 210 130

The additional filler increases the density of the finished capsule to a density

that is substantially close to or above the density of water.

Lactose or micro-crystalline cellulose fillers have a density of 1.5 in solid form.

Thus, in accordance with the present invention, the following standardization for this type of filler (i.e. having a density of 1.5 in solid form) for each respective

capsule size is shown in Table V.

Table V

Initial Capsule Size Volume (ml) New Capsule Size With Filler Volume (ml)

00 0.950 OOel 1.085

0 0.680 00 0.950

1 0.500 00 0.950

2 0.370 0 0.680

3 0.300 1 0.500

4 0.210 2 0.370

5 0.130 2 0.370

Table VI shows new capsule sizes, and the amount of additional filler that can

be added to the new sized capsules and well as the resulting total filler weight.

Table VI

New Capsule Size With Filler Difference Equaling Filler Weight (mg)

Filler Volume (ml) With density 1.5 g/ml OOel 0.135 202

00 0.270 405

00 0.450 675

0 0.310 465

1 0.200 300

2 0.160 240

2 0.240 360 As shown in Tables V and VI, capsule sizes 4 and 5 are increased to size 2.

The difference in a size 5 capsule and a size 2 capsule is 0.24 ml which will

accommodate a filler weight of 360 mg (0.24 ml x 1.5 mg (solid filler density)).

The difference in a size 4 capsule and a size 2 capsule is 0.16 ml which can

accommodate a filler weight of 0.16 ml x 1.5 mg = 240 mg.

Table VIII provides a conversion table that shows initial capsule sizes and

various powder density and weights that can be achieved with each particular

initial size capsule, and new capsule sizes and the various total densities and

weights that can be achieved with each new capsule size. As shown by Table VII,

the various total densities and weights that can be achieved with each new capsule

size are relatively greater than the densities and weights that are possible for the

corresponding initial capsule sizes.

Table VII

Initial Capsule Powder Weight New Capsule Total Weight

Size Density (g/ml) (mg) Size Density (g/ml) (mg)

00 0.6 570 OOel 0.71 772

0.7 665 0.79 867

0.8 760 0.88 962

0.9 855 0.97 1057

1.0 950 1.06 1152 Table VII continued

Initial Capsule Powder Weight New Capsule Total Weight

Size Density (g/ml) (mg) Size Density (g/ml) (mg)

0 0.6 408 00 0.86 813

0.7 476 0.93 881

0.8 544 0.998 949

0.9 612 1.07 1017

1.0 680 1.14 1085

0.6 300 00 1.02 975

0.7 350 1.07 1025

0.8 400 1.13 1075

0.9 450 1.18 1125

1.0 500 1.23 1175

0.6 222 1.01 687

0.7 259 1.06 724

0.8 296 1.11 761

0.9 333 1.17 798

1.0 370 1.22 835 Table VII continued

Initial Capsule Powder Weight New Capsule Total Weight

Size Density (g/ml) (mg) Size Density (g/ml) (mg)

0.6 180 1 0.96 480

0.7 210 1.02 510

0.8 240 1.08 540

0.9 270 1.14 570

1.0 300 1.2 600

0.6 126 0.99 366

0.7 147 1.04 387

0.8 168 1.10 408

0.9 189 1.16 429

1.0 210 1.21 450

5 0.6 78 2 1.18 438

0.7 91 1.21 451

0.8 104 1.25 464

0.9 117 1.29 477

1.0 130 1.32 490

Thus, Table VIII provides a standardization system which provides seven (7)

capsule sizes that accommodate the standard capsule sizes at four or more powder

densities. Thus, the increase in densities is clearly demonstrated. The feature of concentrating the filler at one end of the capsule provides many

advantages. One such advantage is that the end of the capsule having the filler

becomes submerged in the liquid even if the total density of the capsule does not

exceed that of water. This advantage results from the proportionally larger weight

the "filler end" of the capsule. Even if the lighter end of the capsule having the

powder ingredients still floats, the effectiveness of the capsule of the present

invention is still achieved by the weighted filler end of the capsule being

submerged. Another advantage is the improved swallowability of the capsule. A

further advantage is that the proportionally larger weight of the filler end of the

capsule counteracts the buoyancy caused by air bubbles that may be created when

the cap portion of the capsule is joined with the body portion.

In a further embodiment, the cap portion of the capsule is configured so as to

substantially degrade the formation of any bubbles therein when the cap portion of

the capsule is joined with the body portion. In one embodiment, this is achieved

by configuring the end of the cap portion to have a generally flat geometry rather

than a curved or rounded end. In another embodiment, the interior portion of the

cap portion that is adjacent to the end of the cap portion is filled in with the same

material used to formulate the cap portion.

Gravity plays a significant role in the process of swallowing food. The role of

gravity in swallowing food is described in The Human Body, Volume on

"Digestion", pp. 60-61, Torstar Books, 1984 and in The ABC's of the Human

Body, Reader's Digest General Books, page 240, 1987. The relatively greater

weight and/or density of the oral dosage forms of the present invention effect augmentation of the gravitational force that facilitates the downward passage of

the oral dosage forms. Thus, the swallowability of the oral dosage forms is

significantly increased.

Thus, the present invention provides new and improved oral dosage forms that:

a) solve the aforementioned problems discussed above that relate to the

swallowability of oral dosage forms;

b) can be provided in the form of capsules, tablets, gelcaps and softgels;

c) interact with gravity to facilitate prompt and direct movement of the oral

dosage form to the opening of and through the esophagus;

d) results in a relatively faster dissolution rate of the oral dosage form and

relatively faster absorption rate of the medication provided by the oral

dosage form;

e) can be produced with commercially available ingredients; and

f) can be produced without exorbitant manufacturing costs.

The principals, preferred embodiments and modes of operation of the present

invention have been described in the foregoing specification. The invention which

is intended to be protected herein should not, however, be construed as limited to

the particular forms disclosed, as these are to be regarded as illustrative rather than

restrictive. Variations in changes may be made by those skilled in the art without

departing from the spirit of the invention. Accordingly, the foregoing detailed

description should be considered exemplary in nature and not limited to the scope

and spirit of the invention as set forth in the attached claims. Thus, having described the invention, what is claimed is:

Claims

1. An oral dosage form for ingestion with liquid, comprising:

an active ingredient;

an inactive ingredient; and

a substance having a predetermined weight that effects at least partial sinking

of the oral dosage form in the liquid.

2. The oral dosage form according to claim 1 wherein the active ingredient and

inactive ingredient have a combined total weight that is substantially less than the

predetermined weight of the substance.

3. The oral dosage form according to claim 1 wherein the substance is concentrated in a particular portion of the oral dosage form.

4. The oral dosage form according to claim 1 wherein the substance is a filler.

5. The oral dosage form according to claim 4 wherein the filler is a solid.

6. The oral dosage form according to claim 4 wherein the filler is a semi-solid.

7. The oral dosage form according to claim 1 wherein the substance is a binder.

8. The oral dosage form according to claim 4 wherein the filler is coated over the active and inactive ingredients.

9. The oral dosage form according to claim 1 wherein the oral dosage form

further comprises a capsule having a first end and a second end, the active and

inactive ingredients and substance being compressed within the capsule.

10. The oral dosage form according to claim 9 wherein the substance is

concentrated at the first end of the capsule so that when a user desires to ingest the

capsule, the buoyancy of the capsule is substantially reduced and the capsule is

aligned so that the first end of the capsule points in the direction of the pharynx

and the second end of the capsule points in the direction of the mouth thereby

substantially reducing the probability of the capsule being swallowed at an

uncomfortable angle.

11. The oral dosage form according to claim 10 wherein the capsule has indicia

thereon to indicate the first end of the capsule.

12. The oral dosage form according to claim 10 wherein the substance is a filler

which is molded to the inside of the capsule.

13. The oral dosage form according to claim 10 wherein the substance is a filler

which is adhered inside to the inside of the capsule.

14. The oral dosage form according to claim 1 wherein the predetermined

weight effects sinking of the entire oral dosage form in the liquid.

15. The oral dosage form according to claim 1 wherein the active and inactive

ingredients and the substance are configured to form a tablet having a first portion

comprising the active ingredient and a second portion comprising the substance.

16. The oral dosage form according to claim 1 wherein the active and inactive

ingredients and the substance are configured to form a caplet having a first portion

comprising the active and inactive ingredients and a second portion comprising

the substance.

17. An oral dosage form for ingestion with liquid, comprising:

an active ingredient;

an inactive ingredient; and

a substance having a predetermined weight that effects an increase in the

density of the oral dosage form to at least 1.0 g/ml.

18. A tablet for ingestion with a liquid, comprising:

a first end;

a second end;

an active ingredient;

an inactive ingredient; and

a substance having a predetermined density which is concentrated at the first

end so as to effect sinking of at least a portion of the tablet in the liquid.

19. The table according to claim 18 wherein the tablet has a generally conical

shape which tapers from the first end to the second end.

20. The table according to claim 18 wherein the tablet has a generally trapezoidal shape which tapers from the first end to the second end.