Drugs with a slow release

 

Preparative form with delayed release of macrolide compounds contains a composition in the form of a solid dispersion. Macrolide compound in the specified solid dispersion is present in an amorphous state on a solid basis. Preferably macrolide compound is a tacrolimus or 33-epichloro-33-desoxycortisol. Solid Foundation presents a water-soluble polymer, wax, water-insoluble polymer, or a combination. In the method of test for the evaluation of the dissolution profile of formulation with the specified macrolide compound is used, the test solution with a concentration of 0.001-0.1% of the cellulose polymer and the pH is brought to values not higher than 7. New preparative form after oral administration releases the specified macrolide connection slow way and pharmaceutical activity is maintained for a long period. In accordance with the present invention, the frequency of application of pharmacologically active macrolide compounds can be reduced to 1 times a day. New preparative form does not bear the risk of adverse effects from accidental excessive concentrations of macrolide compounds. 2 C. and 18 h.p. f-crystals, 1 table.

1. Preparative form with delayed release of macrolide compounds containing composition in the form of a solid dispersion in which the specified macrolide compound is present in an amorphous state on a solid support, where the time (T, 2%) required for dissolution of 63.2% of the maximum number of macrolide compounds, ranges from 0.7 to 15 hours, measured in accordance with the Pharmacopoeia of Japan, 13 edition, in the test for dissolution 2 (Paddle method, 50 rpm) using a test solution, representing the water of 0.005% solution of hydroxypropylcellulose, with pH is brought to 4.5, in which the macrolide compound is a tricyclic compound of General formula I and its pharmaceutically acceptable salt:where each of the adjacent pairs of R1and R2, R3and R4and R5and R6independently from each other (a) represent two adjacent hydrogen atom, but R2can also be alkyl group, or (b) may form another bond formed between the carbon atoms to which they are linked; R7represents a hydrogen atom, a hydroxy-group, a protected hydroxy-group, or alkoxygroup, or oxoprop together with1; R8and R9independently of the other is foam, alkyl group, substituted by one or more hydroxy groups, alkenylphenol group, alkenylphenol group, substituted by one or more hydroxy groups, or alkyl group substituted by oxopropoxy; X represents oxoprop (a hydrogen atom and a hydroxy-group), (hydrogen atom and a hydrogen atom) or a group represented by the formula-CH2O-; Y represents oxoprop, (a hydrogen atom and a hydroxy-group), (hydrogen atom and a hydrogen atom) or a group represented by the formula N-NR11R12or N-or SIG13; R11and R12independently from each other represent a hydrogen atom, alkyl group, aryl group or tonilou group;
R13, R14, R15, R16, R17, R18, R19, R22and R23independently from each other represent a hydrogen atom or alkyl group;
R24is optionally substituted ring system which may contain one or more heteroatoms;
n represents the integer 1 or 2;
in addition to the above definitions, Y, R10and R23together with the carbon atoms to which they are connected, can represent a saturated or unsaturated 5 - or 6-membered heterocyclic ring containing nitrogen, sulfur and/or alkyl, hydroxy, alkoxy, benzyl, a group of the formula-CH2Se(C6H5and alkyl substituted by one or more hydroxy groups.

2. Preparative form under item 1, in which the macrolide compound is tacrolimus or its hydrate.

3. Preparative form under item 1, in which the macrolide compound is a 33-epichloro-33-desoxycortisol.

4. Preparative form under item 1, in which the solid base selected from the group consisting of water-soluble polymer, wax, water-insoluble polymer or combinations thereof.

5. Preparative form under item 4, in which the solid Foundation is a water-soluble polymer, which is a hypromellose, methylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose or polyethylene glycol.

6. Preparative form under item 4, in which the solid Foundation is wax, which represents the monostearate of glycerol, esters of fatty acids and polyglycerol or ester of fatty acid and of sucrose.

7. Preparative form under item 4, in which the solid Foundation is water-insoluble polymer, which is ethylcellulose or copolymers of methacrylate.

8. Preparative form under item 1, in which the comp is s as excipient and/or lubricants, (2) free from any dezintegriruetsja agent and (3) the particle size of the specified solid dispersion composition is equal to or less than 350 microns.

9. Preparative form on p. 1 containing composition in the form of a solid dispersion, characterized by the fact that the macrolide compound (I) is present in an amorphous state on a solid support selected from the group consisting of 1) hydroxypropylmethylcellulose in a weight amount of 0.1 to 1.0 with respect to 1.0 macrolide compounds (I), 2) ethyl cellulose in a weight amount of 0.1-5 or copolymer of methacrylate in a weight amount of 0.5-5 compared to 1.0 macrolide compounds (I), 3) of ester of fatty acid and of sucrose in a weight amount of 0.2-20 compared to 1.0 macrolide compounds (I), 4) a mixture of hydroxypropylmethylcellulose and ethyl cellulose, in which the hypromellose taken in a weight amount of 0.2-0.4, and ethylcellulose taken in a weight amount of 0.1-5 compared to 1.0 macrolide compounds (I).

10. Preparative form under item 1, in which the composition is in the form of a solid dispersion is characterized in that it includes a macrolide compound (I) in amorphous state in a mixture of hydroxypropylmethylcellulose and ethyl cellulose, in which the hypromellose taken Vescovo lactose, as excipient, free from any cage mill and the particle size of the specified dispersion of the composition is equal to or less than 250 microns.

11. Preparative form on P1, in which the composition is in the form of a solid dispersion is characterized in that it contains, (1) macrolide compound (I) in amorphous state in the hypromellose in a weight amount of from 0.1 to 1.0 with respect to 1.0 macrolide compounds (I), (2) lactose, as excipient, (3) free from any cage mill and the particle size of the specified dispersion of the composition is equal to or less than 250 microns.

12. Preparative form under item 1, in which the time (T, 2%) is from 1 to 12 noon,

13. Preparative form under item 1, in which the time (T, 2%) is from 1.3 to 8.2 hours

14. Preparative form under item 1, in which the time (T, 2%) is from 2 to 5 o'clock

15. Preparative form under item 1, which is represented in the form of powder, fine powder, granules, tablets or capsules.

16. Preparative form under item 1, in which the macrolide compound (I) is present in the form of a fine powder, which has a distribution of particle diameters in the range from 0.1 to 50 μm and/or an average particle diameter of 0.2 to 20 microns.

17. Method of test for dissolution with regard to the e, presented in USP 23, NF18 or European Pharmacopoeia (3rd edition) for estimating the dissolution profile of the solid formulation containing a macrolide compound (I) under item 1, which uses a test solution containing 0.001 to 0.1% of the polymer cellulose.

18. The method according to p. 17, in which the pH of the test solution is brought to a value not higher than 7.

19. The method according to p. 17, in which the cellulose polymer is hydroxypropylcellulose or its equivalent, the concentration of which ranges from 0.001 to 0.1%.

20. The method according to p. 17, in which the test solution is water of 0.005% solution hydroxypropylcellulose with pH increased to values of 4.5.

 

Same patents:

The invention relates to the application of certain monoalkyl esters of fumaric acid or in the form of their salts or in the form of the free acid, individually or in combination with dialkylamino, to obtain pharmaceutical compositions for use in transplantation medicine

The invention relates to containing certain monoalkyl esters of fumaric acid in the form of salts or the free acid individually or in combination with dialkylamino for the treatment of arthritis or multiple sclerosis, as well as reactions "graft versus host"
The invention relates to medicine

The invention relates to new substituted piperidine-2,6-diones of the formula (I)

where Z is-C(R1R2)-CH2or-C(R1)=CH-; R1- phthalimid, when Z is-C(R1R2)-CH2- or one - or twofold substituted by hydroxy, methoxy or amino groups phtalimide radical when Z represents-C(R1)=CH-, R2is hydrogen or C1-6alkyl group; R3is hydrogen, C1-6an alkyl group or aromatic ring system; R4- C1-6alkyl or aromatic ring

The invention relates to pharmacology and medicine, in particular to the preparation of solid dosage forms of the drug rapamycin, which includes a core and a sugar coating

The invention relates to medicine and relates to drugs to prevent transplant rejection, monoclonal antibodies to the CD3 antigen of T-lymphocytes person, hybridoma producing these antibodies, and treatment of patients with reaction acute transplant rejection after kidney transplantation

The invention relates to medicine and organic chemistry and relates to the problem of creating new drugs, inhibiting the proliferation of lymphocytes

The invention relates to the field of pharmacy and related to drug ranolazine

The invention relates to medicine

The invention relates to solid Galanova forms like pills controlled release, designed to be extremely fast, and then prolonged release of one or more active substances

The invention relates to the production and use of the product containing the antibiotic, medicine and veterinary medicine for the treatment of local microbial infections in the hard and soft tissues with a slow release of the active substance

The invention relates to medicine, more specifically to pharmaceutical compositions for the treatment of diseases of the pancreas and digestive disorders associated with liver disease

The invention relates to pharmaceutical industry and relates to solid dosage forms prolongirovannogo steps and the method of obtaining

The invention relates to pharmacology, and relates to pharmaceutical drug omeprazole

The invention relates to the field of medicine

The invention relates to the field of medicine and relates to a method of producing an oral pharmaceutical preparation comprising an inert core and the active layer, dissolving or disintegrating in water obtained from water or water-alcohol suspesions solution containing the active substance having anti-ulcer effect of formula I, II or III), and at least one filler, and gasterosteidae external coating obtained from a solution containing the polymer for Intercollege coating and at least one filler, by drawing on the inert core of the active layer by spraying an aqueous or aqueous-alcoholic suspension solution, drying of the active layer, obtained at the previous stage, and coating the core with an active layer of a solution containing the polymer for Intercollege coating and filler

The invention relates to the field of pharmacy and relates to a method of obtaining a coated spherical granules prostane
Up!