A stable solid dosage forms prednisolone

 

(57) Abstract:

The invention relates to the field of pharmaceutical industry and relates to solid dosage forms containing prednisolone and as auxiliary substances, starch, sugar, PVP with a lot of 30000-40000, stearic acid, and water. The proposed form is more stable. 1 C.p. f-crystals.

The invention relates to pharmaceutical industry and relates to improved compositions of solid dosage forms prednisolone.

Prednisolone pregnadien-1,4-triol-11b, 17A, 21-dione-3,20, or dehydrohydrocortisone well known adrenocorticoids steroid. Prednisolone is digidrirovanny analogue of natural steroid hydrocortisone.

The nature of the activity and close to the prednisone. Drugs prednisolone widely used in medical practice: rheumatism, non-infectious arthritis, bronchial asthma, acute lymphocytic and myeloid leukemia, infectious mononucleosis, neurodermatitis, eczema, and other indications for the use of glucocorticosteroids.

There is evidence of the effectiveness of prednisolone with liver cirrhosis, chronic glomerulonephritis of the prior art a variety of dosage forms of the drug. For example, in an emergency requiring immediate increase of corticosteroids in the blood (acute adrenal insufficiency, shock, asthmatic status, bronchial asthma attacks, and other) using soluble drug prednisolone injection prednizolongemisuktsinat.

For local application, for example, in skin diseases nemikrobnoy etiology (eczema, itching, dermatitis and other) using 0.5% prednizolonovuyu ointment (Unguentum Prednisoloni 0.5%), which applied a thin layer on the skin 1-3 times a day.

In practice eye (keratitis, conjunctivitis, irity, blepharitis, and others) using eye drops containing 0.3% solution of hydrochloride 21-(deoxy-N-methyl-N'-piperazinil)-prednisolone. Appoint 1-2 drops 1-3 times a day.

Prednisolone also assign inwards in the form of tablets. Usually taken from (in severe cases) with 20-40 mg / day. Further to reduce the dose of 5-10 mg per day. These doses are supportive. To stop treatment (as well as the application of other glucocorticoids) should gradually reducing the dose. And at the end of treatment recommended 1-2 times a corticotropin.

Higher doses for adults inside: single 0,015 grams daily 0.1,

In the present who is a white or white with a faint yellowish tinge crystalline powder, almost nerastvorim in water, soluble in alcohol.

When creating his solid dosage forms, there are several problems to be solved. Namely, prednisolon has an unpleasant taste, unstable when stored, and how the majority of drug substances does not possess the ability to direct pelletizing.

Known tableted form of prednisolone, containing as auxiliary substances aluminum hydroxide, calcium diphosphate, sucrose, emulsifier, stearic acid, and stearinovokisly calcium. /The United Kingdom Patent 862376/. However, the content of some of the mentioned auxiliary substances does not meet the requirements of the State Pharmacopoeia.

Known tableted form of prednisolone with a polymer coating of the methyl ester of methacrylic acid. /U.S. patent 4708867 And/. The excipients are not disclosed. Probably, in this case the problem of masking of undesirable taste. However, the application of membranes complicates the technological process and, as a rule, leads to an increase in time raspadaemosti tablets.

Known pharmaceutical composition for regulation of metabolic processes on the basis of the mass ratios of the components. /Patent RF 2153340 C1/. This solution can be considered as the closest analogue. Specified pharmaceutical composition provides a sufficient rate of release of the active agent and certain stability during storage. However, the resulting tablet is not strong enough, do not provide sufficient masking of taste and uniformity of release after administration. The lack of strength leads to destruction in the process of packing, storage, transportation, resulting in reduced shelf life.

The objective of the invention is the development of solid dosage forms prednisolone with considerable strength, optimum bioavailability and improved appearance.

The problem is solved by the creation of solid dosage forms prednisolone on the basis of the following pharmaceutical composition, wt.%:

Prednisolone - 1,9-2,2

Potato starch - 10-12

Sugar - 85-89

Polyvinylpyrrolidone with a molecular weight of 30000-40000 (PVP) - 0,3-0,5

Stearic acid - 0,98-1

Water - the Rest

We offer solid dosage form can be a tablet, granules, capsules filled with granules.

Preimushestvennogo tablet mass, ensure dosage accuracy, mechanical strength, raspadaemost and the storage stability in the case of no compression right active substances, which include prednisolone, provide auxiliary substances.

No pharmaceutical factor does not have such a significant and complex impact on the drug as excipients. Before their introduction was seen as the introduction of indifferent formers. At the present time in the light of biopharmaceutical aspects taken into account the impact on the pharmacokinetics and through it on the efficacy of drugs.

In the proposed composition of the required quality is ensured by the introduction of these ingredients.

Starch provides the required performance raspadaemosti. In addition, because he has dostatochnymi sliding properties, is not entered into the composition, typically used for this purpose talc, which irritate the stomach.

The introduction of PVP in certain quantities significantly affects the stability of granules and tablets. Polyvinylpyrrolidone in the solution forms a spatial grid. Sugar molecules are enclosed in it is large agglomerates, the formation of crystals having a lower fragility and greater flexibility. The greatest effect is achieved when using weight PVP with a molecular mass of 30000-40000. The proposed mixture provides a significant improvement in the taste of the drug. To ensure an even distribution PVP it is introduced in the form of a 5% aqueous solution. You can use a 5% solution of PVP in which the solvent is taken an aqueous solution of 10% alcohol concentration, to accelerate the drying process and reduce microbial contamination.

Stearic acid is used traditionally as a lubricating substance. Stearic acid due to its hydrophobic properties hinders the penetration of body fluids into the porous structure of the tablet. The introduction of PVP reduces the harmful effects stearate through the ability to swell.

Received tableting mass has excellent technical characteristics, including excellent flowability and good bulk density, which ultimately increases the strength of the product.

Another advantage relates to an improved appearance of the obtained tablets, which is important for patients.

As is well known in the process of the activity. The proposed structure preserves its original appearance virtually the entire storage time.

Suggested dosage forms may be obtained in the following way. Powdered sugar, prednisolone, starch loaded into the mixer, mix. The mixture is humidified 5% solution of PVP, granularit air-dried to a residual moisture content of 7.5 to 9.5%. Conduct a dry granulation. The granulate optivault dry starch and stearic acid. The resulting mass tabletirujut or used to fill capsules.

A specific embodiment of the invention.

Mix 250 kg of icing sugar, 6,1 kg prednisolone 24 kg of starch, the mixture is moistened with 5% aqueous PVP solution containing 1 kg of PVP and 19 kg of water, granularit, dried, hold the dry granulation, the resulting mass optivault mixture 8,76 kg of dry starch and 2.9 kg of stearic acid. Get 281 kg ready-to-use tablets containing 0.005 g of prednisolone.

The obtained solid dosage form meets the requirements GFH, has an improved appearance and taste.

The strength of the resulting tablets 1.5 times higher than the closest analogue, 20% reduced microbial colonization.

 

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FIELD: medicine, oncology.

SUBSTANCE: invention relates to a method for treatment of chronic lympholeukosis. Method involves intravenous drop and jet administration of antitumor chemopreparations and carrying out the autochemotherapy. At the 1-st and 8-th day of treatment cyclophosphan in the dose 750 mg/m2, vincristine in the dose 1.4 mg/m2 and doxorubicin in the dose 30 mg/m2 incubated with 200 ml of autoblood are administrated to patients. From the 1-st to 14-th day of treatment prednisolone is used every day in the therapeutic dose. The treatment course is repeated in 30-35 days depending on blood indices and patient state. The total treatment of courses is 4-5. Method provides reducing cardiotoxicity of doxorubicin and cumulative toxicity of chemopreparations that allows carrying out administration of antitumor chemopreparations in the full volume to patients of elderly age groups.

EFFECT: improved method for treatment.

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