Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Matrices
Reexamination Certificate
1997-12-22
2001-02-13
Kulkosky, Peter F. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Matrices
C424S486000, C424S488000
Reexamination Certificate
active
06187343
ABSTRACT:
FIELD OF THE INVENTION
The present invention refers to a proceeding to formulate a compound of sustained and prolonged liberation in the form of granules that maintains the therapeutic action of 4-nitro-2-phenoxymethanesulfonanilide and with a decrease in the fluctuations of plasmatic concentration. This active principle 4-nitro-2-phenoxymethanesulfonanilide is nowadays employed as a medicine sold under the trademark “NIMESULIDE”.
It is a non-steroid anti-inflammatory agent with anti-inflammatory, analgesic and anti-pyretic action indicated for (osteoarthritis, rheumatoid arthritis, chronical inflammatory states of the superior respiratory tract, inflammation of the otolaryngologycal sphere, soft tissues, genital-urinary tract, dysmenorrhea, thrombophlebitis, phlebitis, odontalgia) with adverse effects of the digestive type.
PRIOR ART
Nimesulide or 4-nitro-2-phenoxymethanesulfonanilide, is known since 1974 from the Belgian patent n. 804,812 and U.S. Pat. No. 3,840,897. Both patents define Nimesulide in its preparation and anti-inflammatory activity.
The presentation of the product is in 100 mg and 200 mg compounds of fast or conventional action,
There are other non-steroid anti-inflammatories in the world market, with which it was demonstrated that the forms of programmed and sustained action of continuous liberation, compared to the administration of the same product in its conventional form have less incidence of secondary effects, for example, we have Sodium Diclofenac , Ketoprofen, Indometacine, etc., the forms sustained in continuous liberation granules being in most cases the most secure, efficient and maintaining the plasmatic levels within the therapeutic ranges.
SUMMARY OF THE INVENTION
The present invention, according to the exposed, is a proceeding related to a preparation of controlled liberation of 4-nitro-2-phenoxymethanesulfonanilide (active agent) in multiple granules that liberate gradually the active agent and maintains stable plasmatic concentrations.
The object of the present invention is to achieve an association of this active agent allowing more stable plasmatic concentrations and reducing secondary effects of the digestive type.
This invention of granules or micro-granules containing 4-nitro-2-phenoxymethanesulfonanilide includes:
1. Neutral granules or neutral micro-granules composed of sugar and starch.
2. Incorporation and adherence of the powder-like micronized active agent that adheres to the neutral micro-granules by means of some bonding polymers provided by the solution giving as a result granules commonly denominated fast-action granules, conventional or immediate, and separating the resulting granules into two portions.
3. Adherence of some polymers that form a film form a solution containing them with which a fraction (one portion) of the product of a previous stage is covered, obtaining granules of active principle of sustained and controlled action.
4. Association or mixing of the non-covered granules in 2 with the granules of 3.
The neutral granules are 0.2 mm to 1.8 mm in size, preferably 0.4 mm to 1.4 mm.
According to preferred characteristics of the invention, the active agent is associated to a disintegrator mixed, as a step previous to micronization. The disintegrator may be sodium croscaramellose or crospovidone or other.
The solvents used in 2 for the adherent solution may be acetone, isopropylic alcohol, water or their mixture.
The bonding polymers may be different types of polyvinylpyrrolidines or polyethylene glycols, jellies or their mixtures.
Once the active principle is incorporated and the granules dried, to one part of the same a solution of polymers is added, which gives a sustained and controlled action to the active principle and that form a coating over the granules once the same are dry.
The solvents used may be acetone, isopropylic alcohol, water or their mixtures.
The coating polymers used for giving the sustained and controlled action may be different types of methyl celluloses, different types of hydroxypropylrnethyl celluloses, different types of phthalate of hydroxypropylmethyl celluloses, different types of acrylic polymers (which can be different types of Eudragit L, Eudragit S, Eudragit RL or Eudragit RS or their combinations), different types of shellac and different types of ethyl celluloses; all these polymers may be combined in different proportions.
To this solution it is possible to incorporate plastifiers such as diethylphthalate, dibutylphthalate, polyethylene glycol, triethyl citrate, triacetin, triglycerids of fatty acids, or others.
It is preferable the adding of a lubricant before the drying process, commonly silicon dioxide.
According to other characteristics of the invention the following proportions are preferable for 2.
The proportion of the active principle respecting the rest of the excipients must be between 20% and 90%, and the one of bonding polymers with respect to the rest of the excipients between 0.2% and 5% of disintegrants between 0.5% and 7%.
It is also preferable that the final concentration of granules of active principle to be between 20% and 80% and the size of the granules to be between 0.6 mm and 2 mm, preferably between 0.8 mm and 1.7 mm.
The proportion of acrylic polymers respecting the rest of the polymers may be between 0% and 100%.
The solvent used in the phases 2 and 3 may be 0% to 100% organic or 0% to 100% aqueous.
The final proportion of granules from 2 with respect to the final mixture may be 0% to 50%.
The granules containing 4-nitro-2-phenoxymethanesulfonanilide make possible the preparation and administration of different doses, due to this they may be dosed in capsules of hard jelly in different concentrations.
The association in granules of active principle has a programmed and sustained dissolution system that can be controlled with the Dissolution Equipment USP-type XXIII, page 1791 of the basket type at 100 r.p.m. and each glass with 500 ml of digestive solution, realizing the change in pH in the different hour fractions.
The profile of the solution is the following:
1
st
hour
20%
50%
4
th
hour
55%
85%
8
th
hour
>80%
With this invention one can achieve ways of giving doses of 4-nitro-2-phenoxymethanesulfonanilide of prolonged and sustained action with stable hematic concentrations.
REFERENCES:
patent: 5547683 (1996-08-01), Yano et al.
patent: 5622716 (1997-04-01), Barth
patent: 5711961 (1998-01-01), Reiner et al.
patent: 5744165 (1998-04-01), Geczy
patent: 5756546 (1998-05-01), Pirotte et al.
C.A.114:128992 W.K. Cheung et al. J. Pharm. Sci. (1991) 80(2) 142-8.
Kulkosky Peter F.
Pendorf & Cutliff
LandOfFree
Proceeding for the preparation of the prolonged action... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Proceeding for the preparation of the prolonged action..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Proceeding for the preparation of the prolonged action... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2585999