MXPA00011159A - 8-chloro-6,11-dihydro-11- (4-piperidylidene)-5h-benzo[5,6]cyclohepta[1,2-b]pyridine oral compositions - Google Patents

Abstract

Stable pharmaceutical compositions containing 8-chloro-6,11-dihydro-11- (4-piperidylidene)-5H- benzo[5,6]cycloheptic[1,2-b]pyridine("DCL") and a DCL protective amount of a pharmaceutically acceptable basic salt such as calcium dibasic phosphate and an amount of at least one disintegrant, preferably two disintegrates such as microcrystalline cellulose and starch sufficient to provide dissolution of at least about 80%by weight of the pharmaceutical composition in about 45 minutes and suitable for oral administration to treat allergic reactions in mammals such as man are disclosed.

Description

ORAL COMPOSITIONS OF 8-CL? R? -6,11-DIHYDR? -11- (4- PIPERIPILIDEN) -5H-BENZ0r5,61ClCL0HEPTAp .2-blPIRIPINE BACKGROUND OF THE INVENTION This invention relates to pharmaceutical compositions suitable for oral administration containing 8-chloro-6,11-dihydro-11- (4-piperidylidene) -5H-benzo [5,6] -cyclohepta [1,2-b] pyridine (onwards "decarbonylethoxyloratadine" or ("DCL") and substantially free of DCL decomposition products, and to the use of DCL to prepare such pharmaceutical compositions for treating allergic reactions in mammals. The patent of E.U.A. No. 4,659,716 describes the decarbonylethoxyloratadine which possesses antihistamine properties substantially without sedative properties. This US patent also discloses methods for the preparation of decarbonylethoxyloratadine, pharmaceutical compositions and methods for the use of the compositions for treating allergic reactions in mammals. The patent of E.U.A. No. 5,595,997 discloses pharmaceutical compositions and methods for the treatment of allergic rhinitis using descarbonylethoxyloratadine. The patent application of E.U.A., co-pending and of the same holder that presents it with Minutes No. 08 / 886,766, filed on July 2, 1997 discloses decarbonyl-ethoxyloratadine polymorphs and pharmaceutical compositions containing them. We are not aware of any prior art document that describes the pharmaceutical compositions of the present invention. There is a need to produce pharmaceutical compositions suitable for oral administration to mammals and containing decarboniiethoxyloratadine having constant chemical and physical properties in accordance with demanding health registration requirements of the international and US health registration authorities, for example. , the requirements of the Good Manufacturing Practices ("GMP") of the FDA and the International Conference on Harmonization Guidelines ("ICH").

BRIEF DESCRIPTION OF THE INVENTION We have discovered that the decarbonylethoxyloratadine is decolorized and decomposed in the presence of excipients described in the prior art. We have discovered that these problems are substantially solved when the use of an acidic excipient is avoided and the decarbonylethoxyloratadine is combined with a pharmaceutically acceptable carrier medium comprising a protective amount of DCL of a pharmaceutically acceptable basic salt. Therefore, this invention provides a pharmaceutical composition comprising an effective antiallergic amount of decarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium comprising a protective amount of DCL of a pharmaceutically acceptable basic salt. The pharmaceutical compositions of the present invention contain less than about 1% decomposition such as N-formyl DCL initially, as well as when such compositions are stored at 25 ° C and 60% relative humidity for a period of at least 24 months. In a preferred embodiment, this invention provides a pharmaceutical composition comprising an effective anti-allergenic amount of descarbonyl-ethoxyloratadine in a pharmaceutically acceptable carrier medium wherein said composition contains less than about 1% by weight of N-formyl DCL, preferably less than about 0.8. % N-formyl DCL, and more preferably less than about 0.6% N-formyl DCL. In another preferred embodiment, this invention features a pharmaceutical composition for oral administration comprising an effective antiallergic amount of decarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium comprising a protective amount of DCL of a pharmaceutically acceptable basic salt and an amount of at least one enough disintegrant to provide the dissolution of at least 80% by weight of the pharmaceutical composition in about 45 minutes. This invention also features a pharmaceutical composition for oral administration comprising an effective antiallergic amount of decarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium comprising a protective amount of DCL of a calcium dibasic phosphate., and an amount of microcrystalline cellulose and sufficient starch to provide the dissolution of at least 80% by weight of the pharmaceutical composition in about 45 minutes. In a preferred embodiment, this invention features a pharmaceutical composition for oral administration comprising an effective antiallergic amount of decarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium comprising a protective amount of DCL of a calcium dibasic phosphate, and an amount of microcrystalline cellulose and enough starch to provide a solution of at least 80% by weight of the pharmaceutical composition in about 45 minutes, and containing less than about 1% by weight of N-formyl decarbonylethoxyloratadine. This invention also provides a preferred pharmaceutical composition for oral administration comprising: Ingredient Amount (% by weight) Decarbonylethyloxy-heptadine approximately 0.5-15 Dibasic calcium phosphate dihydrate approximately 10-90 USP Microcrystalline cellulose NF approximately 5-60 NF cornstarch approximately 1-60 Talc USP approximately 0.5-20 This invention also features another preferred pharmaceutical composition for oral administration comprising: Ingredient Amount (% by weight) Descarbonyl-ethoxyloratadine approximately 0.5-15 Dibasic calcium phosphate dihydrate approximately 45-60 USP Microcrystalline cellulose NF approximately 20-40 NF cornstarch approximately 5-15 Talc USP approximately 1-10 This invention also features another preferred pharmaceutical composition for oral administration comprising: Ingredient Amount (% by weight) Descarbonyl-ethoxyloratadine approximately 1-10 Dibasic calcium phosphate dihydrate approximately 50-56 ÚSP Microcrystalline cellulose NF approximately 25-35 NF cornstarch approximately 10-12 Talc USP approximately 2-5 This invention also features the use of DCL for the preparation of the pharmaceutical compositions of the present invention for the treatment of allergic reactions in mammals DETAILED DESCRIPTION OF THE INVENTION During the development of the compositions of the present invention, it was discovered that the decarbonyl-ethoxyloratadine becomes discolored when stored at 75% relative humidity ("RH") and a temperature of 40"C, alone or in combination with various excipients, such as described in U.S. Patent Nos. 4,657,719 and 5,595,997. We found that this color instability in the active ingredient was apparently due to a very small amount of a degradation product caused by the presence of a wide variety of excipients commonly used in oral formulations. , especially a tablet formulation These excipients that were found to be inadequate include acidic excipients including, but not limited to, stearic acid, povidone and crospovidone, and other acidic excipients having a pH in water in the range of about 3 to 5. as well as other excipients such as lactose, lactose monohydrate, sodium benzoate and Behena Glyceryl NF marketed under the trade name of Compritol 888. The presence of acidic excipients such as stearic acid in a solid powder formulation mixture (similar to that of Example 6) containing DCL, lactose monohydrate and stearic acid gave as a result a large amount (14%) of decomposition of decarbonylethoxyloratadine after one week at 40 ° C and 75% RH. When the pharmaceutical compositions of the present invention were subjected to the same conditions For a longer period of time, ie 3 months, less than about 1% decomposition of decarbonylethoxyloratadine was discovered in the pharmaceutical compositions of the present invention. See examples 1-5, 6 and 10 below. Preferably, the pharmaceutically acceptable carrier mode used in the pharmaceutical compositions of the present invention should be substantially free, ie contain less than about 1% by weight of acidic excipients. The main decomposition product of DCL found in the pharmaceutical compositions of the present invention is N-formylDCL. The pharmaceutical compositions of the present invention contain less than about 1% by weight, initially and in periods of up to at least 24 months. Preferably, the pharmaceutical compositions of the present invention contain less than about 0.8% by weight, and more preferably less than about 0.6% by weight of N-formylDCL when such compositions were stored at 25 ° C and 60% RH for at least 24 months. The term "pharmaceutically acceptable basic salts" as used herein means a calcium, magnesium or aluminum salt, or mixtures thereof, including, but not limited to calcium, magnesium and aluminum carbonates, phosphates, silicates and sulfates. Typically, suitable pharmaceutically acceptable basic salts include anhydrous calcium sulfate, calcium sulfate hydrates, such as calcium sulfate dihydrate, anhydrous magnesium sulfate, magnesium sulfate hydrates, dibasic calcium phosphate, anhydrous dibasic calcium phosphate, tribasic calcium phosphate, calcium silicate, magnesium silicate, magnesium trisilicate, aluminum silicate, and magnesium aluminum silicate. The use of calcium phosphate salts is preferred. The use of dibasic calcium phosphate hydrates is more preferred. The use of dibasic calcium phosphate dihydrate is more preferred.

The protective amount of DCL of the pharmaceutically acceptable basic salt used in the compositions of the present invention is usually about 50% by weight of the total composition. The w / w ratio of the protective amount of the pharmaceutically acceptable basic salt to the antiallergic amount of DCL is in the range from about 5: 1 to about 60: 1, preferably from about 7: 1 to about 11: 1, and more preferably from about 10: 1 to about 11: 1. The term "disintegrant" as used herein means a pharmaceutically acceptable material or combination of such materials that provides a pharmaceutically acceptable dissolution index for the compositions of the present invention, preferably a dissolution index for the compositions of the present invention of at least about 80% by weight in about 45 minutes in accordance with the USP paddle dissolution test < 711 > on pages 1791-1793 of USP 23 / NF 18, 1995, UNITED STATES PHAR A-COPEIAL CONVENTION INC. [United States Pharmacopoeia Convention], Rockvile D 20852. Normally, the dissolution rate is measured in 0.1 N HCl at 37 ° C. The preferred dissolution rate of the compositions of the present invention is at least about 80% by weight in about 30 minutes, and more preferably, the dissolution rate of the compositions of the present invention is at least about 90% by weight in approximately 30 minutes. Typically, suitable pharmaceutically acceptable disintegrants include microcrystalline cellulose, starch, for example, pregelatinized starch and corn starch, mannitol, croscarmellose sodium and confectioner's sugar (a mixture of at least 95% by weight of sucrose and corn starch which has been crushed to a fine powder). The pharmaceutical compositions of the present invention contain at least one, preferably at least two, and more preferably two pharmaceutically acceptable disintegrants in the w / w ratio of about 1: 1 to 3: 1. In a preferred embodiment of the present invention, the two pharmaceutically acceptable disintegrants are cellulose and starch, preferably corn starch, in the w / w ratio of about 2: 1 to about 3: 1. The w / w ratio of the protective amount of the pharmaceutically acceptable basic salt to the amount of the pharmaceutically acceptable disintegrant (s) on the scale from about 1.1: 1 to 2: 1, preferably from about 1.2: 1 to about 1.75: 1 , and more preferably from about 1.20: 1 to about 1.25: 1.

Unexpectedly, we have discovered that when decarbonylethoxyloratadine was combined with a carrier medium comprising dibasic calcium phosphate, and microcrystalline cellulose in the absence of prior art excipients such as stearic acid or lactose, we have produced a pharmaceutical composition that was stable to discoloration when It is stored for 4 weeks in Petri dishes open at a temperature of 40 ° C and relative humidity of 75%. In a preferred embodiment of the present invention, the carrier medium also contains corn starch and talc. Instead of corn starch it can be replaced by pregelatinized starch; talc can be replaced by PEG 8000. Dibasic calcium phosphate can be replaced by calcium sulfate dihydrate, although the use of calcium dibasic phosphate is preferred. No significant changes (less than about 1-2% by weight) in physical appearance were observed, moisture content, chemical test of descarbonyl-ethoxyloratadine and on the dissolution index of the tablet formulations when a preferred embodiment of the present invention of example 10 was stored in plastic bottles or in blister packs for up to 9 months at 25 ° C / 60% RH or 30 ° C / 60% RH or for up to 6 months at 40 ° C / 75% RH. The decarbonylethoxyloratadine used in the present invention can be prepared according to Example VI of the US patent. No. 4,659,716. Decarbonyl ethoxyloratadine exists in two polymorphic forms (form 1 and form 2) which can be prepared in accordance with examples 1-3 and the procedures of the US patent application, co-pending from the same owner as the present one with Minute No. 08 / 886,766 filed on July 2, 1997. These two polymorphic forms were interconverted during the manufacture of the formulations of tablets of the present invention. While either of the two polymorphic forms can be used, form I is preferred.

PHARMACEUTICAL COMPOSITIONS The pharmaceutical compositions of this invention contain an anti-allergy-effective amount of decarbonyl-ethoxyloratadine as the active ingredient, and a pharmaceutically acceptable carrier medium which may include, in addition to specific amounts of calcium dibasic phosphate and microcrystalline cellulose, other inert pharmaceutically acceptable ingredients that can be solid or liquid. The solid form compositions include powders, tablets, dispersible granules, capsules and suppositories. These inert pharmaceutically acceptable media ingredients include one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, tablet disintegrating agents or encapsulating materials. The solid dosage forms of the pharmaceutical compositions of the present invention are suitable for oral administration and include powders, tablets, dispersible granules, capsules, mouths and suppositories. In the powders, the carrier medium is a finely divided solid which is a mixture with the finely divided active ingredient. In the tablet, the active ingredient is mixed with carrier medium having the necessary binding properties in suitable proportions and compacted in the desired shape and size. The effective antiallergic amount of DCL in the pharmaceutical compositions of this invention, for example, powders and tablets is from about 0.5 to about 15 percent, preferably from about 0.5 to 10 percent by weight and more preferably from about 1 to 10 percent. one hundred in step. The term "compositions" is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active ingredient (with or without other carriers) is surrounded by the carrier medium, which thus is in association with the same. Similarly, capsules are included. The effective antiallergic amount of decarbonyl ethoxyloratadine for oral administration ranges from about 1 to 50 mg / day, preferably from about 2.5 to 20 mg / day and more preferably from about 5 to 10 mg / day in single or divided doses. The most preferred amount is 5 mg, once a day. Naturally, the precise dosage and the dosage regimen can be varied depending on the requirements of the patients (for example, their sex, age) as well as the severity of the allergic condition being treated. The determination of the appropriate dosage and the dosage regimen for a particular patient will be within the knowledge of the intervening physician. Decarbonylethoxyloratadine possesses antihistaminic properties. These antihistamine properties have been demonstrated in conventional animal models, such as the prevention of histamine-induced lethality in guinea pigs. The antihistaminic activity of form 1 and polymorph form 2 of decarbonyl ethoxyloratadine has also been demonstrated from a monkey model.

General Experimetal Part Decarbonylethoxyloratadine can be prepared according to Example VI of USP No. 4,659,716. Dibasic calcium phosphate dihydrate [Ca (H2P? 4) 2- H2?] Is available from Rhone Poulenc Rorer, Shelton, CT 06484; Microcrystalline cellulose is available from FMC Corporation Food & Pharmaceutical Products, Philadelphia, PA 19103, NF corn starch is available from National Starch & Chemical Corp., Bridgewater, NJ 08807 and Talc USP is available from Whittaker, Clark and Daniels, Inc., South Plainfield, NJ 07080.

Method of manufacturing the pharmaceutical compositions of the present invention in the form of tablets The following procedure illustrates the formulation of tablets: Preparation of starch paste 1. Prepare a 10 p / p starch paste by dispersing the portion of the corn starch paste in a portion of purified water in a suitable container equipped with an agitator. 2.- While mixing, heat the contents of the container until 95 ° C and maintain this temperature for 30 minutes. 3. Add an additional amount of purified water to the heated mixture and allow the starch paste thus formed to cool to about 50 ° C. 4.- While mixing, add the descarboniletoxiloratadina to the starch paste.

Granulation 5. To a suitable fluid bed processing vessel, load the dibasic calcium phosphate dihydrate, a portion of the corn starch and a portion of the microcrystalline cellulose. Place the processing vessel in a fluid bed processor. 6.- Fluidize the powder bed and mix for 3 minutes. 7.- Begin by granulating the powder by pumping the starch paste from step 4 in the fluidized bed at a suitable spray rate (for a batch size of 600,000 tablets, the spray rate was 500 ml / min) and a temperature of bed of 22 ° C. 8. - Continue drying the granulation at 60 ° C until the granulation has a final drying loss of 2% or less. 9.- Pass the dried granulation through a suitable sieve or mill. 10.- Load the granulation in a suitable mixer and add the necessary amount of the remaining portion of microcrystalline cellulose, corn starch and talcum. Mix for 5 minutes to produce a uniform powder mixture. The resulting mixture can be filled into suitable two-piece hard gelatin capsules in a suitable encapsulation machine. The mixture can also be compressed to an appropriate size and weight in a suitable tablet machine.

Tableting 1. Compress the final powder mixture in a suitable tablet press with a target tablet weight of 100 mg and a hardness of 7-9 s.c.u. (Strong-Cobb Units) Tablets can be film coated by loading compressed tablets into suitable coating equipment that has a rotating tray and heater. The tablets in the rotating tray are contacted at a temperature of about 30-50 ° C with a coating solution formed by dissolving clear or colored coating materials in purified water. After the tablets are Fully coated, a polishing powder can be added to the coated tablets to provide polished coated tablets. Alternatively, the color coating material can be added as a dry powder in step 5 or 10, preferably in step 5 of the granulation phase of the process. It is preferred that the color coating material is preferably substantially free, ie, < about 1%, or more preferably completely free of offensive excipients such as lactose.

EXAMPLE 1-5 Follow the manufacturing procedure mentioned above using the ingredients mentioned below and compress the powder mixture into tablets.

Ina windings 1 mq 2.5 mq 5 mq 7.5 mq 10 mq resistance resistance resistance resistance resistance (mq / tab) (mq / tab) (mq / tab) (mq / tab) (mq / tab) Decarbonyl 1 2.5 5 7.5 10 ethoxyloratadine Dihydrate 53 53 53 53 53 dibasic calcium phosphate USP Cellulose 32 30.5 28 25.5 23 microcrystalline NF Starch 11 11 11 11 11 corn NF Talc USP 3 3 3 3 3 Total 100 100 100 100 100 EXAMPLES 6-9 The tablet formulations of Examples 6-9 were prepared according to the procedure of Examples 1-5.

EXAMPLE 6 Ingredients Mg / tablet Descarbonyletoxiloratadine 10 Lactose monohydrate 69 Corn starch 18 Stearic acid 2 Silicon dioxide 1 EXAMPLE 7 Ingredients Mq / tablet Descarbonylethoxyloratadine 10 Lactose monohydrate 59 Microcrystalline cellulose 8 Pregelatinized starch 15 Sodium croscarmellose 5 Silicon dioxide 1 Stearic acid 2 EXAMPLE 8 Ingredients Mq / tablet Decarbonylethoxyloratadine 2.5 Dibasic calcium phosphate 78.5 Corn starch dihydrate 18 Magnesium stearate 1 EXAMPLE 9 Ingredients Mg / tablet Decarbonylethoxyoratadine 2.5 Microcrystalline cellulose 10 Mannitol 71.5 Pregelatinized starch 15 Magnesium stearate 1 The tablet formulations of Examples 6-9 prepared according to the procedure of Examples 1-5 were rapidly discolored when placed in open petri dishes after less than a week under a temperature of 40 ° C and a relative humidity of 75% Color Stability of Formulated Tablets of Examples 1-5 The color stability of the aforementioned tablets of Examples 1-5 was studied in open petri dishes under a stressed condition of a temperature of 40 ° C and 75% relative humidity After storage in open petri dishes under this condition for 4 weeks, it was found that the tablets of Examples 1-5 were free from discoloration and remained white. When decarbonylethoxyoratadine was formulated with other excipients such as lactose and stearic acid and formed into tablets, according to the procedures of Examples 1-5, the tablets of Examples 6-9 were rapidly discolored after less than a week under the same conditions of storage. A mixture of solid powder formulation (similar to that of the tablets of Example 6) containing DCL, lactose monohydrate and stearic acid in the ratio p / p / p of 1: 7: 0.2 also decomposed rapidly after less for one week under the same storage conditions of a temperature of 40 ° C and 75% relative humidity; The classical trial for descarbonyl-ethoxyloratadine in this solid powder formulation was about 86% of the initial amount and the color of the formulation was pink.

EXAMPLE 10 The procedures of Examples 1-5 were followed except that the formulation of Example 3 was compressed into tablets and film coated and polished. Ingredients mg / tablet Decarbonylethoxyoratadine 5.0 Calcium phosphate dihydrate 53.00 dibasic USP Cellulose microcrystalline NF 28.00 Corn starch NF 11.00 Talc NF 3.00 Film coating (blue) 6.00 Film coating 0.6 (transparent) Polishing wax1 0.01 1. - The polishing wax is a 1: 1 w / w mixture of Carnuba wax and white wax.

The stability of the formulated tablets of Example 10 The chemical test, the physical properties and the photostability of the formulated tablets of Example 10 were measured in samples placed in high density polyethylene bottles and blister packs. 5 No significant change (< 1-2%) in physical appearance, moisture content, chemical trial of descarbonyl-ethoxyloratadine and dissolution rate was observed when the tablets of example 10 were stored in plastic bottles or packages of blisters for up to 9 months at 25 ° C / 60% relative humidity ("HR") or at 30 ° C / 60% HR or for up to 6 months at 40 ° C / 75% RH. A small amount of degradation, for example, N-formylDCL, was observed in the tablets stored in bottles (approximately 0.8%) in blisters (approximately 1.2%) at 40 ° C / 75% relative humidity for 6 months; only about 0.2-0.3% of the degradation product was observed in any sample of tablets stored in blister packs or bottles for 9 months at 25 ° C / 60% or at 30 ° C / 60% RH. The International Conference on Harmonization Impurity Guidelines ("ICH") is expected to be completed for a 5 mg tablet stored for 24 months at the International Conference on Harmonization ("ICH"). 25 ° C / 60% RH or for 12 months at 30 ° C / 60% RH of 1% by weight of the tablet. When the tablets in an open dish were subjected to ICH light conditions for one week at 25 ° C, the total amount of decomposition products was 0.34% by weight.

EXAMPLE 11 The procedures of Example 10 were followed except that Lagoon Blue was added as a dry powder to the step of the granulation phase and the formulation was then compressed into tablets.

Ingredients mg / tablets Decarbonyletoxylloratadine 5.0 Calcium phosphate dihydrate 53.00 dibasic USP Microcrystalline cellulose NF 27.72 Corn starch NF 11.00 Talc NF 3.00 FD8.C Blue No. 2 Lake 0.28 Total 100.00 The formulation of Example 11 is expected to have a chemical test, and physical properties and photostability similar to that observed for the formulation of Example 10. Many modifications and variations of this invention can be made without departing from its spirit and scope, as will be evident for those skilled in the art. The specific embodiments described in the present invention are offered by way of example only, and the invention should be limited only by the terms of the appended claims, together with the full scope of equivalents to which such claims are entitled.

Claims (28)

1. NOVELTY OF THE INVENTION CLAIMS 1. A pharmaceutical composition for oral administration comprising an effective anti-allergenic amount of descarbonyl-ethoxyloratadine in a pharmaceutically acceptable carrier medium comprising a protective amount of DCL of a pharmaceutically acceptable basic salt and at least one pharmaceutically acceptable disintegrant, wherein the carrier medium Pharmaceutically acceptable is substantially free of acidic excipients.
2. 2. The pharmaceutical composition according to claim 1, further characterized in that at least one pharmaceutically acceptable disintegrant is in an amount sufficient to provide dissolution of at least 80% by weight of the composition pharmaceutically in 45 minutes 3. - The pharmaceutical composition according to claim 1, further characterized in that the w / w ratio of the protective amount of DCL of the pharmaceutically acceptable basic salt to said disintegrant is in the range of 1: 1 to 2: 1, preferably of 1.5: 1 to 2: 1 and preferably from 1.25: 1 to 1.75: 1. 4. The pharmaceutical composition according to claim 1, further characterized in that the basic salt Pharmaceutically acceptable is a calcium, magnesium or aluminum salt or mixtures thereof. 5. The pharmaceutical composition according to claim 1, further characterized in that the pharmaceutically acceptable basic salt is a calcium phosphate salt. 6. A pharmaceutical composition according to claim 1, which contains less than 1% by weight of N-formyldescarbonyletoxylloratadine after storage at 25 ° C and 60% relative humidity for at least 24 months 7.-. The pharmaceutical composition according to claim 1, further characterized in that the w / w ratio of the protective amount of DCL of the pharmaceutically acceptable basic salt to the effective anti-allergenic amount of decarbonyl-ethoxyloratadine is the scale of 5: 1 to 60: 1 preferably from 7: 1 to 11: 1 and more preferably from 10: 1 to 11: 1. 8. A pharmaceutical composition for oral administration comprising an effective anti-allergenic amount of descarbonyl-ethoxy-dilatadine in a pharmaceutically acceptable carrier medium comprising a protective amount of calcium dibasic phosphate DCL, an amount of microcrystalline cellulose and of sufficient starch to provide a dissolution of at least 80% by weight of the composition pharmaceutically in 45 minutes, wherein the pharmaceutically acceptable carrier medium is substantially free of acidic excipients. 9. - A pharmaceutical composition according to claim 8, which contains less than 1% by weight of N-formyl-decarbonyl-ethoxyloratadine after storage at 25 ° C and 60% relative humidity for at least 24 months. 10. A pharmaceutical composition for oral administration comprising an effective anti-allergenic amount of decarbonyloxyethoxyloratadine in a pharmaceutically acceptable carrier medium comprising a protective amount of calcium dibasic phosphate DCL, an amount of microcrystalline cellulose and of sufficient starch to provide a dissolution of at least 80% by weight of the pharmaceutical composition in 45 minutes, and containing less than 1% by weight of N-formyl decarbonylethoxyloratadine after storage at 25 ° C and 60% relative humidity for at least 24 months, wherein the pharmaceutically acceptable carrier medium is substantially free of acidic excipients. 11. A pharmaceutical composition according to claim 8, comprising: Inquired Quantity (% by weight) Decarbonylethoxyloratadine 0.5-15 Dihydrate phosphate dibasic 10-90 calcium USP Cellulose microcrystalline NF 5-60 Corn starch NF 1-60 Talc USP 0.5-20 12. - A pharmaceutically composition according to claims 8, 9 and 10, comprising: Ingredient Amount (% by weight) Decarbonylethyloxytadite 0.5-15 Dibasic phosphate dihydrate 45-60 calcium USP Microcrystalline cellulose NF 20-40 Corn starch NF 5-15 Talc USP 1-10 13. - A pharmaceutical composition according to any preceding claim, further characterized in that the amount of decarbonylethoxyloratadine is in the range of about 1 to 10 weight percent. 14. A pharmaceutical composition according to claims 8, 9 and 10, comprising: Ingredient Amount (% by weight) Decarbonyletoxyloratadine 1-10 Dibasic phosphate dihydrate 50-56 calcium USP Microcrystalline cellulose NF 25-35 Corn starch 10-12 Talc USP 2-5 15. - A pharmaceutical composition of any preceding claim, which initially contains less than 1% by weight of N-formyl decarbonyl-ethoxyloratadine. 16. A pharmaceutical composition comprising an effective anti-allergic amount of descarbonyl-ethoxyloratadine in a carrier medium A pharmaceutically acceptable salt comprising a protective amount of DCL of a pharmaceutically acceptable basic salt, wherein the pharmaceutically acceptable carrier medium is substantially free of acidic excipients. 17. The pharmaceutical composition according to claim 16, further characterized in that said composition further comprises at least one pharmaceutically acceptable disintegrant. 18. The pharmaceutical composition according to claim 17, further characterized in that at least one pharmaceutically acceptable disintegrant is in an amount sufficient to provide dissolution of at least 80% by weight of the pharmaceutical composition in 45 minutes. 19. The pharmaceutical composition according to claim 18, further characterized in that the w / w ratio of the protective amount of DCL of the pharmaceutically acceptable basic salt to said disintegrant is in the range of 1: 1 to 2: 1, preferably from 1.5: 1 to 2: 1 and preferably from 1.25: 1 to 1.75: 1. 20. The pharmaceutical composition according to claim 17, further characterized in that the pharmaceutically acceptable basic salt is a calcium, magnesium or aluminum salt or mixtures thereof. 21. - The pharmaceutical composition according to claim 17, further characterized in that the pharmaceutically acceptable basic salt is a calcium phosphate salt. 22. A pharmaceutical composition according to claim 17, which contains less than 1% by weight of N-formyl-decarbonyl-ethoxyloratadine. 23. The pharmaceutical composition according to claim 18, further characterized in that the ratio w / w of the protective amount of DCL of the pharmaceutically acceptable basic salt to the effective anti-allergic amount of decarbonyl-ethoxyloratadine is the scale of 5: 1 to 60: 1, preferably from 7: 1 to 11: 1 and more preferably from 10: 1 to 11: 1, wherein the pharmaceutically acceptable carrier medium is substantially free of acidic excipients. 24. A pharmaceutical composition comprising an effective anti-allergenic amount of descarbonyl-ethoxyloratadine in a pharmaceutically acceptable carrier medium wherein said composition contains less than 1% by weight of N-formylDCL, preferably less than 0.8% of N-formylDCL, and more preferably less than 0.6% of N-formylDCL. 25. The pharmaceutical composition according to claim 24, further characterized in that said composition is adapted for oral administration. 26. The pharmaceutical composition according to claim 24, further characterized in that said composition has been stored at 25 ° C and 60% relative humidity for at least 24 months. 27. A pharmaceutical composition comprising 5 mg of decarbonylethoxyloratadine in a pharmaceutically acceptable carrier medium. 28. The pharmaceutical composition according to claim 27, further characterized in that said composition contains less than 1% by weight of N-formylDCL.