MX2007006348A - Microemulsion containing pirfenidone. - Google Patents

Abstract

The invention relates to a pirfenidone microemulsion composition which is advantageous over other orally administered pharmaceutical forms known in the prior art, such as tablets, capsules, suspensions and solutions.

Description

MICROEMULSION CONTAINING PIRPHENIDONE FIELD OF THE INVENTION.

The present invention relates to a formulation containing pirfenidone, which is prepared in a microemulsion that offers advantages over other pharmaceutical forms of oral administration known in the state of the art, such as tablets, capsules, suspensions and solutions.

BACKGROUND OF THE INVENTION. -methyl-1-phenyl- (1H) -pyridone, of formula; CH3 is a drug that has been applied in the restoration of tissues with lesions that occur with fibrosis and for the prevention of fibrotic lesions. This compound, called Pirfenidone, is itself a known compound and its pharmacological effects have been described in, for example, Japanese applications KOKAI Nos. 87677/1974 and 1284338/1976, as an anti-inflammatory agent including the effects anti-pyretic and analgesic. U.S. Patent Nos. 3,839,346, published October 1, 1974, 3,974,281, published August 10, 1976, 4,042,699, published August 16, 1977, and 4,052,509, published October 4, 1977, describe methods for obtaining Pirfenidone, as well as its use as an anti-inflammatory agent. The anti-fibrotic activity of 5-methyl-1-phenyl- (1H) -pyridone is described in Mexican patent 182,266.

Different resources and treatments have been used, but to date none of them is really effective. Pirfenidone has demonstrated its effectiveness as an anti-fibrotic agent, in different pathologies and organs, as has been demonstrated in previous studies, where we have observed an effect on the fibroblasts and the collagen produced by them, both in experimental models and in clinical trials Soft gelatin capsules.

Soft gelatine capsules are used in the pharmaceutical, cosmetic, nutritional and veterinary industries. This diversity demonstrates the versatility of the soft gelatin capsule, the content within a soft gelatin capsule can be a liquid, semi-solid mixtures, non-aqueous solutions or suspensions, all due to the water-soluble nature of gelatin. Soft gelatine capsules are containers or unit packages, formed by two soft gelatin films, which contain the active ingredient among them. The soft gelatin capsule can be prepared in various shapes and sizes depending on the design needs of the medicine. The advantages offered by soft gelatin capsules over other pharmaceutical forms of oral administration are: - Unit dosage, that is, in a single piece; - by their manufacturing process are hermetically sealed compartments: - they are easy to administer; - allow the differentiation of the product, through of colors and shapes; there is uniformity and precision between one dose and another; they are proof of adulterations, because they are sealed hermetically of origin; they have much better stability than other means of oral administration; they have high bioavailability and rapid absorption; they have the preference of the consumer, due to their safety, appearance and asepsis; offer asset protection against pollution, light and oxidation; unpleasant odors and flavors are avoided by taking the encapsulated assets in this way; they are the means of oral administration easy to pass through the throat; they can be used as a means of oral, rectal, vaginal and ophthalmic administration; the filling accuracy is from 1 to 2.5% depending on the asset to be filled; They feature elegant, bright and eye-catching appearance of the finished product; They can be manufactured in different colors and sizes, responding well to the needs of drug administration or design, can be manufactured transparent or colorful, with solid colors, natural transparency, solid colors in combination of two tones, transparent in two tones, polished or matt finishes.

MICROEMULSION The microemulsions are differentiated from the emulsions by the fact that the former are formed spontaneously, which corresponds to a minimum free energy state of a simple phase. Emulsions on the other hand require the addition of energy (mechanical and / or heat) for their formulation. From this it follows that the interfacial tension between the continuous and dispersed phases in the microemulsion is low. When emulsions with micro droplets (also called mini emulsions) are coagulated by temperature changes. The micro emulsions on the contrary are always stable to these changes. Thus, the simplest way to differentiate between micro emulsions and emulsions with micro droplets is to use repeated cycles of freezing and heating in both systems. The micro emulsion will return to its original state of stability, since its restoration is controlled by diffusion while the emulsion is separated into the original components that gave rise to it.

OBJECT OF THE INVENTION It is an object of the present invention to provide a composition for oral administration comprising Pirfenidone. Also, it is an object of the present invention to provide a composition for the manufacture of a soft gelatin capsule. Another object of the present invention is to provide a soft gelatin capsule containing a microemulsion whose active principle is Pirfenidone. Among other objects of the present invention is to provide a medicament in a soft gelatin capsule for use as an anti-fibrotic and anti-inflammatory agent.

SPECIFICATION OF THE INVENTION COMPOSITION OF THE CAPSULE The soft gelatin capsules are made from the following components: gelatin between 38% and 42¾ preferably between 39% and 40% and more preferably between 39.9 and 40% by weight of the composition, purified water between 38% and 42% preferably between 39% and 40% and more preferably between 39.9 and 40% by weight of the composition, glycerin between 18% and 22% preferably between 19% and 20% and more preferably between 19.5 and 20% by weight of the composition, at least one conservative between 0.15% and 0.20% preferably between 0.16% and 0.19 % and more preferably between 17 and 18% by weight of the composition, titanium dioxide between 0.25% and 0.30% preferably between 0.27% and 0.29% and more preferably between 0.28 and 0.29% by weight of the composition and a dye (yellow color No. 10 FD¡C) between 0.0095% and 0.015% preferably between 0.0097 and 0.013% and more preferably between 0.0099 and 0.011% by weight of the composition. An example of composition of the gelatin bark is shown in table 1: COMPONENT QUANTITY (mg)% Purified water 227.31 40 Gelatin 237.31 40 Glycerin 111.31 19.5 Matilparaben sodium 0.822 0.14 Propylparaben sodium 0.204 0.03 Titanium dioxide 1.62 0.28 Yellow coloring No.10 FD¡C 0.056 0.001 A second composition can be prepared from the components shown in Table 2: These two compositions are shown by way of examples, but are not limiting in any way to the scope of the description of the present invention.

COMPOSITION MICROEMULS IONABLE PIRFENIDONA The microemulsifiable composition of Pirfenidone object of the present invention also comprises; absolute ethyl alcohol, dl-alpha tocopherol acetate, Pluracol E-400, Cremophor RH-40 and Amaranth Oil. Where pirfenidone is present in an amount between 8. 58% and 10.38% by weight of the composition, alcohol absolute ethyl in an amount between 6.92% and the 15. 57%, the dl-alpha tocopherol acetate in an amount between 12.58% and 28.30%, the pluracol E-400 in a amount between 9.43% and 21.23%, the Cremophor RH-40 in an amount between 25.16% and 56.60% and the Oil of Amaranth in an amount between 6.29% and 14.15%.

An example of the microemulsifiable composition of Pirfenidone is shown below: A second example for a microemulsifiable composition of Pirfenidone is exemplified as follows: COMPONENT QUANTITY (mg) Pirfenidone 95 Absolute ethyl alcohol 110 Pluracol E-400 150 Cremophor RH-40 400 Vitamin E 200 The compositions are shown by way of examples but are not limiting in any way to the scope of the description of the present invention.

Claims (1)

1. CLAIMS 1. - A microemulsionable composition of Pirfenidone which also comprises absolute ethyl alcohol, dl-alpha tocopherol acetate, Pluracol E-400, Cremophor RH-40 and Amaranth Oil. 2. The composition of claim 1, characterized in that it comprises Pirfenidone between 8.58% and 10.38% by weight of the composition, absolute ethyl alcohol between 6.92% and 15.57%, dl-alpha tocopherol acetate between 12.58% and 28.30%, pluracol E-400 between 9.43% and 21.23%, Cremophor RH-40 between 25.16% and 56.60% and Amaranth Oil between 6.29% and 14.15%. 3. The composition of claim 1, characterized in that it is in unit dosage form and has the following composition: composition of claim 1, characterized because in the form of a unit dose and has the following composition: 5. - A composition for the formation of a soft gelatin shell, characterized in that it comprises gelatin between 38% and 42%, preferably between 39% and 40% and more preferably between 39.9 and 40% by weight of the composition, purified water between 38% and 42% preferably between 39% and 40% and more preferably between 39.9 and 40% by weight of the composition, glycerin between 18% and 22% preferably between 19% and 20% and more preferably between 19.5 and 20 % by weight of the composition, at least one preservative between 0.15% and 0.20% preferably between 0.16% and 0.19% and more preferably between 17 and 18% by weight of the composition, titanium dioxide between 0.25% and 0.30% preferably between 0.27% and 0.29% and more preferably between 0.28 and 0.29% by weight of the composition and a colorant between 0.0095% and 0.015% preferably between 0.0097 and 0.013% and more preferably between 0.0099 and 0.011% by weight of the composition. 6. A composition according to claim 5, wherein the soft gelatin shell comprises: 7. - A composition according to claim 5, wherein the soft gelatin shell comprises: 8. - A unit dosage form comprising a soft gelatin shell and a composition containing Pirfenidone as the active agent. 9. - The unit dosage form comprising a soft gelatin shell whose composition is any of those described in claims 5, 6, or 7, and a composition according to any of claims 1 to 4. 10. - The unit dosage form of any of claims 8 and 9, which is prepared in the form of a capsule for oral administration. 11. The use of the unit dosage form of any of claims 8 to 10, for the restoration of tissues with fibrotic lesions and for the prevention of fibrotic lesions.