oral solid formulations are the object of the present invention , containing , as active ingredient , a molecule useful in the ibd therapy , characterized by the association of different polymers or mixtures of polymers , each one soluble starting from a ph value different from the others and ranging from 6 to 7 . such formulations release the active ingredient in a multiphasic way , each phase occurring at a different ph value ranging from 6 to 7 . particularly preferred is the association of three polymers or mixtures of polymers , soluble starting from a ph value different one from the other and ranging from 6 to 7 , which causes a triphasic release of the active ingredient . preferred is the combination of a polymer or a mixture of polymers soluble starting from ph 6 , a polymer or a mixture of polymers soluble starting from ph 6 . 5 and a polymer or a mixture of polymers soluble starting from ph 7 . in this case the active ingredient is released by the invention formulations in a triphasic way , preferably in the following ph - dependent quantities : ph = 6 10 - 60 % of the released active ingredient ph = 6 . 5 10 - 60 % of the released active ingredient ph = 7 10 - 60 % of the released active ingredient . even more preferably the active ingredient release occurs in the following ph - dependent quantities : ph = 6 30 - 35 % of the released active ingredient ph = 6 . 5 30 - 35 % of the released active ingredient ph = 7 30 - 35 % of the released active ingredient . they can , furthermore , be utilized for the administration of other active ingredients useful in the ibd therapy , among which to be mentioned are steroids , such as prednisone , prednisolone or budenoside , antibiotics and anti - inflammatories . the formulations of this invention can be in the form of capsules containing micro - tablets , tablets , granules or microgranules or pellets , or in the form of multilayer tablets , or in the form of sachets or dispensers containing granules or microgranules or pellets . with the term micro - tablet we identify a tablet having a diameter equal or inferior to 2 mm . each capsule contains micro - tablets , tablets , granules or microgranules or pellets of three types , each one presenting a coating including a polymer soluble starting from a ph value ranging from 6 to 7 , such ph value being different for each one of such three types . similarly , granules or microgranules or pellets of three types are dosable in sachets or dispensers for granules . preferably such coating contains from 20 to 100 % of said polymer or mixture of polymers . such coating can include also a fatty acid at 10 - 20 carbon atoms , preferably stearic acid , usually in a quantity ranging from 0 to 40 % and a pharmaceutically acceptable plasticizer , preferably diethylphtalate , usually in a quantity ranging from 0 to 40 %. preferably in each capsule or sachet such three types are contained in proportions suitable to obtain the above described triphasic release profiles ; the best ratio is 1 : 1 : 1 . according to a particularly preferred application , in each capsule , one third of such micro - tablets , tablets , granules or microgranules or pellets exhibits a coating including a polymer or a mixture of polymers soluble starting from ph 6 , another third includes a coating constituted of a polymer or a mixture of polymers soluble starting from ph 6 . 5 and the last third presents a coating including a polymer or a mixture of polymers soluble starting from ph 7 . preferably , the polymer soluble starting from ph 6 is eudragit l or cellulose acetatephtalate , or hydroxypropylmethylcellulosephtalate or hydroxypropylmethyl - celluloseacetatesuccinate type l . the mixture of polymers soluble starting from ph 6 . 5 is eudragit l or hydroxypropylmethylcellulosephtalate or hydroxypropylmethyl - celluloseacetatesuccinate type l in a mixture 1 : 1 with eudragit s . the polymer soluble starting from ph 7 is eudragit s or hydroxypropylmethylcelluloseacetatesuccinate type m . the above mentioned granules or microgranules or pellets are constituted of the active ingredient and pharmaceutically acceptable excipients , commonly used in the preparation of granules ; their preparation happens by processes of granulation , nucleation , layering , extrusion and spheronization , that are well - known to the experts of modified release oral dosage forms . the above micro - tablets and tablets are made up of the active ingredient and pharmaceutically acceptable excipients commonly used in the preparation of tablets . they can optionally include also from 5 to 35 % of a polymer or a mixture of polymers soluble at a ph ranging from 6 to 7 , from 0 to 10 % of a fatty acid at 12 - 20 carbon atoms , preferably stearic acid , and from 0 to 10 % of a pharmaceutically acceptable plasticizer , preferably diethylphtalate . in this case , the polymer or mixture of polymers contained in the micro - tablets or in the tablets is the same as that included in their coating . alternatively , the invention formulation can be in the form of multilayer tablets : these are made up of three layers , each one including , besides the active ingredient and the excipients commonly utilized for the preparation of tablets , a polymer or mixture of polymers soluble starting from a ph value ranging from 6 to 7 and different from the one in which the polymer or the mixture of polymers of the other two layers dissolves . preferably each tablet contains from 5 to 35 % of polymer . optionally , such tablets can contain also a fatty acid at 12 - 20 carbon atoms , preferably stearic acid , usually in a quantity ranging from 0 to 10 % and a pharmaceutically acceptable plasticizer , preferably diethylphtalate , commonly in a quantity ranging from 0 to 10 %. preferably such layers contain amounts of the active ingredient suitable to obtain the above described triphasic release profiles ; preferably the quantities of active ingredient in the three layers are equal . according to a particularly preferred application , the internal layer includes a polymer or a mixture of polymers soluble starting from ph 7 , one of the external layer includes a polymer or a mixture of polymers soluble starting from ph 6 . 5 and the second external layer includes a polymer or a mixture of polymers soluble starting from ph 6 . preferably such polymer soluble starting from ph 6 is eudragit l or cellulose acetatephtalate , the mixture of polymers soluble starting from ph 6 . 5 is a mixture 1 : 1 of eudragit l / eudragit s and the polymer soluble starting from ph 7 is eudragit s . the multilayer tablets present furthermore a coating preferably including a polymer or a mixture of polymers soluble starting from ph 6 . 0 , like , for example , eudragit l . optionally such coating includes also a fatty acid at 12 - 20 carbon atoms , preferably stearic acid , and / or a plasticizer , preferably diethylphtalate . preferably such coating contains from 20 to 100 % of said mixture of polymers , from 0 to 40 % of fatty acid and from 0 to 40 % of diethylphtalate . in case the active ingredient is mesalazine , the formulation is prepared having a dosage ranging from 100 to 3000 mg . sachets and dispensers for granules or microgranules or pellets contain a mesalazine dosage ranging from 100 and 3000 mg . 4 kg of mesalazine have been granulated on a fluid bed with tangential insert . the active ingredient powder has been sprayed with ethanol or with a mixture 1 : 1 of water / ethanol containing pvp at 20 % o . the granules have been selected with a net of 1200 μ and the not conform fraction has been micronized , suspended in water / ethanol 1 : 1 and applied on the granules . the so obtained granules have been transferred into desiccator and then tested to check the potency and the dissolution rate , obtaining the results reported in table 1 . the dissolution tests of table 1 and of the following tables have been carried out with paddle apparatus , usp . 500 g of granulate of example 1 have been coated , in two steps , with 600 g of an ethanolic solution containing 7 % p / p of eudragit s , 8 . 4 g of diethylphtalate and 9 g of stearic acid , utilizing a fluid bed equipped with bottom spraying insert . for the first coating 400 g of the indicated solution have been utilized ; the remaining quantity has been applied in a second coating . after each coating step the granules have been dried prior to being tested . the dissolution tests have provided the results reported in table 2 . 500 g of product manufactured according to example 1 have been coated in a fluid bed with bottom spraying insert with 600 g of an ethanolic solution containing : 7 % p / p of eudragit l , 8 . 4 g of diethylphtalate and 9 g of stearic acid . the granules obtained have been dried and tested : the dissolution data obtained are summarized in table 3 . 500 g of granulate of example 1 have been coated with 600 g of a solution containing 7 % p / p of a mixture 1 : 1 of eudragit l and eudragit s , 8 . 4 g of diethylphtalate and 9 g of stearic acid , in a fluid bed equipped with bottom spraying insert . the granules obtained have been dried and tested , obtaining the results reported in table 4 . the granules manufactured as described in examples 2 . 1 , 2 . 2 . and 2 . 3 have been mixed in the ratio 1 : 1 : 1 and inserted into capsules in a quantity corresponding to 400 mg of mesalazine for each capsule . the capsules have been tested to evaluate the mesalazine dissolution profile : the results are reported in table 5 . in a high speed granulator 8 kg of mesalazine have been wetted with 1 . 2 kg of a polyvinylpyrrolidone binder solution at 20 % in ethanol and processed to obtain granules having high density and low friability . the granules having granulometry between 500 and 1000 microns have been selected ; the granules with a granulometry not included in said interval have been micronized , suspended in water / ethanol 1 : 1 and applied on the fraction of 500 - 1000 microns . the so obtained granules have been divided into three portions and each of these portions has been coated separately in a fluid bed as described in the following example . 2 . 5 kg of granules obtained in example 3 have been transferred in a fluid bed and coated with 3 . 0 kg of the ethanolic solution of eudragit s utilized in the example 2 . 1 . the product obtained has been dried and tested to check the mesalazine release profile . the results obtained in the dissolution test are reported in table 6 . 2 . 5 kg of granules obtained in example 3 have been transferred in a fluid bed and coated with 3 . 0 kg of the ethanolic solution of eudragit l utilized in the example 2 . 2 . in table 7 the results of the dissolution test are reported . 2 . 4 kg of granules obtained in example 3 have been transferred in a fluid bed and coated with 3 kg of the ethanolic solution of eudragit s and eudragit l utilized in the example 2 . 3 . the granules obtained have been dryed and tested . in table 8 the dissolution test results are reported . the granules coated according to the above examples 4 . 1 , 4 . 2 and 4 . 3 have been mixed in the ratio 1 : 1 : 1 and inserted into capsules in a quantity corresponding to 500 mg of mesalazine / capsule . the so obtained capsules have been tested to evaluate the mesalazine release profile . the results obtained in the dissolution test are reported in table 9 . 3 kg of mesalazine have been granulated with 0 . 8 kg of a solution at 20 % of polyethylene glycol 4000 in ethanol / water 1 : 2 and the resulting granulate has been extruded and spheronized to obtain granules with an average diameter of 1200 μ . the so obtained granules , coated as described in the examples 4 . 1 , 4 . 2 and 4 . 3 , have been mixed in the ratio 1 : 1 : 1 and inserted into capsules in a quantity corresponding to 500 mg of mesalazine / capsule . the so obtained capsules have shown the dissolution profile reported in table 10 . in a high speed granulator 4 kg mesalazine have been wetted with 0 . 600 kg of a polyvinylpyrrolidone binder solution at 20 % in ethanol and granulated to have high density and low friability granules . the granules having granulometry between 150 - 400 microns have been selected ; the granules having granulometry not included in this interval have been micronized and regranulated . the so obtained granules have been divided in three portions and each of such portions has been coated separately in a fluid bed as described in the following example . 7 . 1 ) 0 . 800 kg of the granules obtained in the example 6 have been transferred in a fluid bed and coated with 1 . 5 kg of the eudragit s ethanolic solution utilized in the example 2 . 1 . the product obtained has been desiccated and tested to evaluate the mesalazine release profile . the results of the dissolution test are reported in table 11 . 0 . 800 kg of the granules obtained in the example 6 have been transferred in a fluid bed and coated with 1 . 5 kg of the eudragit l ethanolic solution utilized in the example 2 . 2 . in table 12 are reported the results of the dissolution test . 0 . 800 kg of the granules obtained in the example 6 have been transferred in a fluid bed and coated with 1 . 5 kg of the eudragit s and eudragit l ethanolic solution utilized in the example 2 . 3 . the granules obtained have been desiccated and tested . in table 13 are reported the results of the dissolution test . the granules coated according to the above examples 7 . 1 , 7 . 2 and 7 . 3 , have been mixed in the ratio 1 : 1 : 1 ; the so obtained mixture has been dosed in monodose sachets containing 1200 mg mesalazine per sachet ; the so obtained sachets have been tested to evaluate the mesalazine release profile . the results obtained in the dissolution test are reported in table 14 . 8 kg of mesalazine , 1 . 3 kg of eudragit s and 0 . 3 kg of stearic acid , micronized , have been granulated adding 1 kg of an ethanolic solution containing 10 % p / p of eudragit s and 0 . 03 kg of diethylphtalate . such granulate has been prepared as described in the example 8 . 1 , utilizing the following substances and relative quantities : such granulate has been prepared with the same procedure utilized in the example 8 . 1 , using the following substances and relative quantities : mesalazine 8 kg eudragit s 0 . 65 kg eudragit l 0 . 65 kg stearic acid 0 . 30 kg eudragit s in ethanol 5 % p / p eudragit l in ethanol 5 % p / p diethylphtalate 0 . 03 kg 1 . 020 kg of granulate of example 8 . 1 have been mixed with 30 g of magnesium stearate and pressed with round punches of 6 mm of diameter to obtain tablets having an average weight of 175 mg . a quantity equal to 950 g of so obtained tablets has been film - coated in a rotating pan utilizing an ethanolic solution containing 7 % p / p of eudragit s , 2 . 2 % p / p of diethylphtalate and 2 % p / p of stearic acid . the film - coating process has been stopped when it has been reached a weight increase per each tablet of 10 mg . 1 . 020 kg of granulate of example 8 . 2 have been utilized to prepare tablets as described in example 9 . 1 , which have been filmed in a rotating pan utilizing 800 g of an ethanolic solution containing 7 % p / p eudragit l , 2 . 2 % diethylphtalate and 2 % stearic acid . the film - coating process has been protracted up to the obtainment of a weight increase per each tablet of 10 mg . 1 . 020 kg of granulate of example 8 . 3 have been utilized to prepare tablets as described in example 9 . 1 , which have been then film - coated in a rotating pan utilizing 800 g of an ethanolic solution containing 7 % p / p of a mixture 1 : 1 of eudragit s and eudragit l , 2 . 2 % of diethylphtalate and 2 % of stearic acid . the tablets obtained in the examples 9 . 1 , 9 . 2 and 9 . 3 have been inserted into gelatin capsules size “ 0 ” in the following quantities : the mesalazine release profile from the so prepared capsules has been analyzed through dissolution tests , obtaining the results reported in table 15 . the so obtained granules have been mixed with 80 g of magnesium stearate and pressed to obtain micro - tablets , 2 mm in diameter , and average weight of about 6 mg . 500 g of the so obtained micro - tablets have been film - coated in a fluid bed with 600 g of an ethanolic solution containing 7 % of eudragit s , 8 . 4 g of diethylphtalate and 9 g of stearic acid . 500 g of the micro - tablets obtained have been treated as described in the example 10 . 1 with 600 g of an ethanolic solution containing 7 % of eudragit l , 8 . 4 g of diethylphtalate and 9 g of stearic acid . 500 g of the above obtained tablets have been treated as described in the example 10 . 1 with 600 g of an ethanolic solution containing 7 % of a mixture 1 : 1 of eudragit l and eudragit s , 8 . 4 g of diethylphtalate and 9 g of stearic acid . the tablets obtained as described in the examples 10 . 1 , 10 . 2 and 10 . 3 have been mixed between them in the ratio 1 : 1 : 1 and inserted into capsules in a quantity equal to 800 mg of mesalazine . the results obtained by the dissolution test on the so obtained capsules are reported in table 16 . 2 . 5 kg of mixture of granules and magnesium stearate of example 10 have been pressed to obtain tablets with a diameter of 6 mm and an average weight equal to about 140 mg . 700 g of such tablets have been coated with the solution described in example 10 . 1 up to the obtainment of a weight increase equal to about 13 mg per tablet . 700 g of such tablets have been coated with the solution described in example 10 . 2 up to the obtainment of a weight increase equal to about 13 mg per tablet . 700 g of such tablets have been coated with the solution described in example 10 . 3 up to the obtainment of a weight increase equal to about 13 mg per tablet . the tablets obtained as described in the examples 11 . 1 , 11 . 2 and 11 . 3 have been inserted in the ratio 1 : 1 : 1 into capsules in a quantity equal to 400 mg mesalazine . the results obtained with the dissolution test on the so obtained capsules are reported in table 17 . the granulates obtained in the examples 8 . 1 , 8 . 2 and 8 . 3 have been lubricated with 1 % magnesium stearate and then pressed in the ratio 1 : 1 : 1 with oval punches having a length of 18 mm and a width of 8 . 6 mm utilizing a three layer tableting machine . the three granulates have been pressed in sequence to obtain tablets having an average weight of about 630 mg . in particular , it has been pressed first the granulate of example 8 . 2 , then that of example 8 . 1 and finally that of example 8 . 3 . 1 kg of the so obtained tablets has been then film - coated in a rotating pan with 800 g of an ethanolic solution containing 7 % of eudragit l , 11 g of diethylphtalate and 10 g of stearic acid . the film - coating of the tablets has been stopped after having reached a weight increase of 45 mg per each tablet . the results of the dissolution test of the so obtained tablets are reported in table 18 . the clinical evaluation has been conducted administering the formulation of example 2 . 4 in comparison with commercial formulations of mesalazine ( asacol ® and clayersal ®). twelve healthy subjects having an average age of 41 . 3 years ( between 20 . 2 and 71 . 4 ) have been treated , 4 per group , according to the following scheme : active ingredient drug mesalazine per dose mesalazine per day asacol ® tablets 400 mg 1200 mg claversal ® tablets 500 mg 1500 mg formulation of example 2 . 4 400 mg 1200 mg the treatment has lasted 8 days . on the 5 th , 6 th and 7 th day of treatment 7 . 5 mg of sodium picosulfate have been administered to the patients to facilitate the intestinal washing . the last dose has been administered on the 8 th day at 6 . 00 a . m . the patients have neither eaten nor drunk up to 9 . 00 a . m ., and have been submitted to an intestinal washing through intake of a suitable dose of polyethylene glycol . after each liter of polyethylene glycol solution the patients have taken orally 5 mg of metoclopramide . for the complete intestinal cleaning 3 l solution were needed . the ileoscopy has been carried out between 2 . 00 p . m . and 3 . 00 p . m ., after sedative analgia . the biopsies have been carried out according to this order : the biopsic fragments have been immediately weighed and frozen in liquid nitrogen , then kept at − 80 ° c . such procedure has been carried out within 30 minutes from the sample collection . the mesalazine content has been determined in ng / mg of humid weight through hplc . the results are illustrated in the following table 19 , where the quantity of mesalazine , in ng / mg , noticed in each analyzed region , is reported . from table 19 it turns out that the formulation of this invention allows to obtain more homogeneous tissue concentrations of mesalazine than those obtained with the reference formulations , enabling , therefore , the active ingredient to perform its activity in all anatomical areas . the comparative bioavailability of the formulation referred to in example 2 . 4 , test preparation 500 mg , has been investigated in a single dose , crossover trial versus a reference product of the same strength , already marketed . the investigational formulations have been administered to 12 healthy male volunteers with a wash - out period from 7 to 14 days . the study showed that serum concentrations of test preparation as compared to those of the reference product : as in the blood only the part of the drug that does not exert any therapeutic activity is detected , the above data prove that the available drug in the sites of action in the intestinal lumen is more elevated and in more constant concentrations .
oral solid pharmaceutical compositions with ph - dependent multiphasic release , containing , as active ingredient , a molecule useful in the inflammatory bowel disease therapy , are described ; being such compositions suitable to the release of the active ingredient in the intestinal tract .