FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
"CHEWABLE /OR TWIST-OFF CAPSULE DELIVERY SYSTEM
2. APPLICANT:
(a) NAME: GELTEC PRIVATE LIMITED
(b)NATIONALITY: Indian Company incorporated under the Indian Companies ACT, 1956
(c) ADDRESS: Capsulation Premises, Deonar, Sion-Trombay Road, Mumbai - 400088, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION:
The following specification describes the invention.

Field of invention:
This invention relates to an improved chewable/or twist off soft gelatin capsule, the shells of which comprises gelatin, water, plasticizer and starch. More particularly, the invention relates to an improved soft gelatin capsule as drug delivery system.
Background of the invention:
Oral drug administration necessitates devising drug administration devices that helps achieving various therapeutic objectives like bioavailability, shelf life, patient compliance etc. Though all the above objectives are necessary, patient compliance is an important issue that has prompted drug delivery devices that helps patients to easily administer the drug.
Liquid and especially concentrated liquid pharmaceutical compositions offer many advantages over solid compositions. Liquids are easy to swallow and provide an excellent vehicle for the uniform delivery of pharmaceutical actives and also provide a rapid onset of pharmacologic action, since the composition does not have to disintegrate and dissolve in the gastrointestinal tract. Concentrated liquid compositions are ideally suited for encapsulation within a soft gelatin shell, to provide a portable and easy-to-swallow soft, and flexible capsule.
Soft gelatin encapsulation of a solution or dispersion of a pharmaceutical agent in a liquid vehicle or carrier offers many advantages over other dosage forms such as compressed, coated or uncoated solid tablets or bulk liquid preparations. Gelatin encapsulation of a solution or dispersion permits accurate delivery of a unit dose, an advantage which becomes especially important when relatively small amounts of the active ingredient must be delivered, as in the case of certain hormones. Such uniformity is more difficult to achieve via tabletting process wherein solids must be uniformly mixed and compressed, or via incorporation of the total dose of active ingredient into a bulk liquid carrier which must be measured out


prior to each oral administration. Soft gelatin capsules are also more easily transported by patients than bulk liquids, since only the required number of doses need be removed from the package.
Soft gelatin encapsulation further provides the potential to improve bioavailability of pharmaceutical agents. Relatively insoluble active ingredients can be dispersed in a liquid or gelled carrier to provide faster absorption upon rupture of the capsule. For example, Miskel et al.(US3851051)disclose soft gelatin capsules which contain aqueous solutions or suspensions of active ingredients in a water-soluble gel lattice matrix which is formulated to rapidly disperse upon rupture of the capsule shell.
A well-recognized difficulty in the art of soft gelatin encapsulation is that the gelatin capsule shell can be deleteriously affected by water or other aqueous solvents present in the capsule fill material. One way in which previous investigators have addressed the problem of the delivery of an aqueous fill material in a water soluble capsule shell has been by modifying the composition of the shell. For example, the shells of soft gelatin capsules have been modified in order to produce an increased stability of the shell to withstand dissociation by an aqueous capsule fill material. Szymanski et al (US3865603) disclose gelatin compositions which are "extended" by adding to the gelatin of the shell fluidity starches and thermally modified starches, both of which are chemically modified by the addition of mono reactive moieties.
Kreuger in US2580683 discloses the addition of non-hygroscopic water soluble substances(i.e., substances whose physical characteristics will not be appreciably altered by the effects of water vapour) to the shell of gelatin capsules which have been filled with aqueous solutions of an ingredient compounded with a hygroscopic substance. Sugars are disclosed as the preferred non-hygroscopic constituent of the capsule wall. Raising the


sugar content of the capsule wall is disclosed as a means of reducing the required content of dry material in the fill.
Morishita (Japanese Patent Application no 56-89833) discloses a shell material formed from gelatin, tannic acid, water and "sugar type ethyl alcohol, grape sugar or a similar sugar". Morishita further discloses that the acidic shell encloses non-acidic filler.
Kobayashi et al (US0730926) discloses a soluble, filmy substance used as a wrapper for medicines, either powders or pills, which comprise isinglass or gelatin, starch and water. A film of substantially equal parts of starch and gelatin is disclosed which is made of edible ingredients and which is soluble in saliva or gastric juice. The film disclosed by kobayashi is used by wrapping it around medicines and then putting the wrapped medicine in water so that the film swells and softens.
Soft gelatin based compositions commonly employed to form the shells of soft gelatin capsules are not palatable or edible as those terms are understood in the art. Although they are not toxic, most shells yield a gummy unpleasant tasting, intractable mass in the mouth if they are chewed. However, a gelatin shell which is chewable and edible in the sense that it is pleasant tasting and can be readily fragmented, dissolved and swallowed would be advantageous for a number of reasons.
For example, in instance where a user is in medical distress from the sudden attach of a condition such as angina pectoris, rapid release of the active ingredient in the fill material of a capsule into the mouth is essential. The shell of a capsule must dissolve rapidly, without leaving any traceable, insoluble residue in the mouth upon which the distressed user might choke. Additionally, when the active ingredients are palatable and thus need not be swallowed whole, soft gelatin capsules provide a convenient delivery vehicle for a unit dosage of the active ingredient. Children and elderly users may not be able to swallow entire capsules,


tablets, or pills. Soft gelatin capsules allow these users to easily chew and ingest the active ingredients within capsules in a palatable form. Hence, there exists a need in the art for a soft gelatin capsule comprising a shell which is readily chewable & edible and twist-off to dispense the medicament in oral cavity.
Objective of the invention:
An object of the invention is to provide a soft gelatin capsule comprising a shell which is chewable to deliver the medicament in mouth.
Another objective of the invention is to provide soft gelatin capsule which can be twist-off to dispense the medicament in oral cavity. In yet another objective the invention provides soft gelatin capsules which is devoid of stickiness thus eliminating the problem of sticking together during storage.
Summary of the invention:
In accordance with the above objectives, the present invention provides a chewable/or twist-off soft gelatin capsule which comprises:
a) a soft gelatin shell composition which comprises about 20-40% gelatin; about 25-45% water; about 15 to 35% plasticizer and about 5 to 20% of starch; and wherein said shell encloses
b) a soft gelatin capsule fill material.
Preferably the soft gelatin capsule of the invention provides a pharmaceutical unit dosage form of an active substance such as a drug, mineral or a vitamin. However, the capsule may also provide a means to deliver a confection, a breath-freshener, or a similar non-toxic ingestible material.
Detailed description of the invention:
In accordance with the present invention, there is provided a chewable/or twist-off soft gelatin capsule which comprises a shell comprising water,


gelatin, plasticizer and an amount of starch effective to render said shell dispersible and soluble in the mouth of the user; and a soft gelatin capsule fill material in which an active ingredient, preferably an active agent, is dispersed or dissolved.
Soft gelatin:
The starting gelatin material used in the manufacture of capsules is obtained by the partial hydrolysis of collagenous material such as the skin, white connective tissues or bones of animals. Type A gelatin is derived mainly from porcine skins by acid processing and exhibits an isoelectric point between pH 7 and pH 9, while Type B gelatin is derived from alkaline processing of bones and animals (bovine) skins and exhibits an isoelectric point between pH 4.7 and pH 5.2. Gelatin may also be derived from the skin of cold water fish. Blends of Type A and Type B gelatins can be used to obtain a gelatin with the requisite viscosity and bloom strength characteristics for capsule manufacture. The shell of the present capsule comprises gelatin upto 40%, preferably upto35%. The gelatin may be of Type A or Type B or a mixture thereof. Bloom Numbers, an indicator of gelatin strength, may range from about 60 to 300.
The starting gelatin material of the present capsule is modified to produce "soft gelatin" by the addition of a plasticizer to the gelatin. The addition of plasticizer is necessary in order to achieve the softness and flexibility of the capsule shell required for chewability. Useful plasticizers of the present invention include Glycerin (1,2,3-propane triol), D-sorbitol(D-glucitol), or similar low molecular weight polyols. The shell of the present capsule comprises about 15 to 35%, preferably 18 to 30%; and most preferably about 20 to 25% of plasticizer. The preferred plasticizer of the invention is glycerin.
Water
The shell of the present soft gelatin capsule comprises about 25 to 45%, preferably about 28 to 45% and most preferably about 30 to 34% of water.


The water content of the shell aids in its rapid dissolution upon contact with saliva and other gastric fluids present in the mouth.
Starch:
In order to augment the taste and chewability of the capsule shell, as well as to assist the rapid dissolution of the shell upon chewing, the present capsule shell further comprises a starch.
Starch is present in the shell of the present soft gelatin capsule in a weight percentage of about 5 to 20%; and preferably about 8 to 15%. It has been discovered that the presence of the starch in these amounts in the capsule shell augments the chewable and palatable properties of the shell as well as assists in its rapid dissolution upon chewing. The presence of the potato starch in the present capsule shell ensures that the shell will quickly dissolve as it is chewed. This quick-dissolving property makes the present capsule particularly effective for administration of medicine or other biologically -active substances to persons in medical distress, to the elderly, to children, or to animals, all of whom may not be able to swallow a hard capsule or to chew a soft capsule for a prolonged period. In addition, the pleasant, sweet taste imparted by the potato starch makes the present capsule more palatable than capsules which are tasteless or unpleasant-tasting. This also acts as anti-adhesion agent which prevents capsules to sticking together during storage.
Soft gelatin capsule fill material
The present soft gelatin capsule shell will enclose a pre selected quantity of a fill material. Preferably, this enclosed fill material will constitute a pharmaceutical unit dosage form of a biologically active substance such as a drug, mineral or vitamin. The fill material of the present capsule can take one of several forms: i) liquid; (ii) semisolid;(iii) solid; or (iv) gel.
In the liquid form of the present capsule fill material, one or more biologically-active compounds can be dispersed or dissolved in a non-toxic


liquid base. Preferably the liquid base of the present capsule fill material is a vegetable oil. Suitable vegetable oils for use in the present capsule fill material include corn oil, peanut oil, safflower oil, sunflower oil and soybean oil. The liquid base may also comprise thinkers, acidulants and emulsifier. The liquid solvent base of the present capsule may optionally be mixed with sweeteners such as sucralose, xylitol, aspartame, sachharin; and flavorings such as citric acid, lemon oil, nutmeg oil, mixed fruit, orange, peppermint, rose, spearmint or spearmint and strawberry and emulsifier like lecithin. Thickeners like bees wax, hydrogenated vegetable oil are used to suspend the active ingredients in the oil base.