US2390088A

US2390088A - Enteric gelatin capsule shell or envelope

Info

Publication number: US2390088A
Application number: US459598A
Authority: US
Inventors: Sereck H Fox; Opferman Laurene Paterson
Original assignee: GELATIN PRODUCTS CORP
Current assignee: GELATIN PRODUCTS Corp
Priority date: 1942-09-24
Filing date: 1942-09-24
Publication date: 1945-12-04
Anticipated expiration: 1962-12-04

Description

Patented Dec. Q, 1945 ENTERIC GELATIN CAPSULE SHELL OR ENVELOPE Sereck H. Fox, Birmingham, and Laurens Paterson Opferman, Detroit, Mich., assignors to Gelatin Products Corporation, Detroit, Mich., a corporation oi Michigan No Drawing. Application September 24, 1942, Serial No. 459,598

4 Claims.

This invention relates to an improved gelatin envelope or protective enclosure for medlcaments or other substance which envelope or enclosure is enteric.

This improvement is herein described as particularly relating to an enteric capsule shell but it may be embodied in an envelope or enclosure surrounding a tablet or medicament in any suitable dosage form.

Heretofore, medicaments intended for intestinal dispersion and having individual dosages in tablet. pill, or capsule form have been coated with various types oi enterlc coatings. Gelatin is the commonly used capsule shell material and gelatin capsule shells have been so coated but so far as is known there has not been available a gelatin or other sheet of enteric character which possessed the necessary physical characteristics for use as capsule shell material.

One form of enteric coating usedwas a phthalic acid ester of cellulose. such material was applied as were other enteric coating .materials as a coating to the outer surface the medicamentwhich might be in the form of a pill or tablet, or applied as a coating to the outer surface of a capsule shell. Such enteric material was alway applied as a coating to an otherwise seli' contained medicament dosage. If the medicament was in fluid form it was first capsulated as within a gelatin shell and the enteric material was applied as a coating to the capsule shell. Such coating materials lacked the elasticity and flexibility of gelatin and were not suitable for use in sheet form as capsule shells. Such coating material possessed the disadvantage under certain circumstances of breaking down through developgnent of cracks or fissures therein. They were particularly unsuitable when used as a coating upon a gelatin capsule shell not only for the above reasons but tor the further reason that due to change in size and shape or the capsule shell as a result of accidental deformation or temperature variations, the coating film tended to rupture and break.

This invention is directed toward the provision of an improved gelatin envelope or sheet material which may be used in the formation of an envelope 0! capsule shell and which will protect the medicament from the action of the stomach secretions upon passage or the medicament therethrough but which will break down upon exposure to the intestinal secretions, releasing the medicament therein. We have discovered that when a suitable cellulose derivative, which is water soluble, such as the sodium salt of cellulose acetate phthalate, is added in relatively small percentage such as live to ten per cent to a suitably plasticized commercial gelatin solution, and such solution used to form a capsule shell or envelope for a medicament, and when such capsule shell is subjected to a suitable tanning treatment that the capsule so formed will pass through the stomach without release of its contained medicament but will break down in the intestines sufllciently to release the medicament. The gelatin solution may be the conventional one of one-third gelatin, one-third water and one-third glycerin, or it may be a relatively harder gelatin mixture wherein the glycerin content is reduced.

For example, we have found that a suitable gelatin mixture may be prepared as follows:

Grind the cellulose acetate hydrogen phthalate on a micro pulverizer or otherwise suitably pulverize the same. Determine the theoretical amount of sodium acid carbonate required to neutralize and dissolve the cellulose acetate phthalate which commercially varies in degree of esterlfication. Mix the required amount of sodium bicarbonate with the phthalate as by dry mixing in a Hobart mixer for 10-15 minutes. Add 8 lbs. of C. water to the mixture and mix until all phthalate has gone into solution. Allow to stand overnight to permit complete reaction and evolution of all gas. Add 4 /2 lbs. glycerin to 5 lbs. water; add gelatin with mixing. Allow to soak overnight. Next morning add the phthalate solution to the soaked gelatin with stirring. Break up all large aggregates of gelatin. Put in gel tank and melt at 60 C. Maintain on heat until air and CO2 free. Such a gelatin solution should be free from undissolved phthalate. The pH should not exceed 7-7.5.

Such a gelatin solution will form a suitable band or sheet capable of use in a capsulating machine and may be used to form a, capsule shell enclosing a suitable medicament or to form other enveloping enclosures.

A suitable tanning treatment is to formalize 2 I a,seo,oss

the capsule shell thus prepared in a 1% iormaldehyde solution for forty-rive or sixty seconds tollowedbywashinginwateranddrying. Thetannlng may be accomplished inother suitable ways such as through the employment of chromic acid of the shell is resistant to attack by the stomach juices whereby the capsule passes through the stomach without release of its content. When the capsule enters into the intestines however. the shell breaks down suiliciently to'release the content material. It is believed that while the tanned gelatin is still resistant to solution, be cause of its tanning, that the cellulose derivative traction of the shell responds to the intestinal secretions and the phthalate reverts to the soluble alkali salt providing openings through the shell which cause it to break down and release its content material.

It is understood that the water soluble form so oi the cellulose derivative changes to the water insolubleiorminthestomachduetotheralatively blah acid environment iolmd there.

What we claim: 1. A content material surrounded by a tanned gelatin envelope which has dispersed throughout a sumcient amount of an alkali metal salt oi cellulose acetate phthalate to render the envelope responsive to the action 01 the intestinal secrelO tions to release the content substance while re- 'sisting dissolution in the acid stomach secretions.

2. A medicament surrounded by a tanned gelatin envelope which envelope contains in dispersed admixture with a selatin 5% to 10% b7 15 webht of an alkali metal salt of cellulose acetate phthalate.

3. A medicament surrounded by a tanned gelatin envelope which envelope contains in dispersedadmixturcwiththeselatinasmallper-Y zo centage of sodium salt of cellulose acetate phthalate in sui'ilcient amount to cause the envelope to release the medicament in response to intestinal secretions.

4. An enteric capsule shell consisting of a tanas ned gelatin envelope which contains in dispersed admixture with a gelatin an alkali metal salt of cellulose acetate phthalate.

BERECK H. FOX. LAUREN! PA'I'ERBON OFFER-MAN.