according to a preferred embodiment , the invention relates to a solid oral drug form , characterized in that at least a part of the api that it comprises is contained in microparticles , and in that it comprises , firstly , means ( a ) for preventing , or at the very least making very difficult , the crushing of the microparticles containing the api , and secondly , means ( b ) for making very difficult the misuse of the api after a possible liquid extraction carried out for the purposes of misuse . an overcoating for protection of the microparticles of api having at least one of the following characteristics : viscoelastic properties for absorbing the energy dissipated during crushing , a low cohesive strength for promoting breaking of the overcoating and not of the microparticles , a low surface energy for promoting slipping of the microparticles during crushing , an ability to form a paste under high shear , and / or excipients in the free state , i . e . not contained in nor supported by microparticles , and capable of acting against , or even preventing , the crushing of the microparticles of api . the preferred anti - crushing means ( a ) are particles coated with an overcoating having specific physicochemical properties . according to a specific embodiment of the drug form according to the invention , at least a part of the microparticles of api are microparticles , preferably microcapsules , for modified release of api . notably , the microparticles of api have an average diameter of less than or equal to 1000 μm , preferably between 50 and 800 microns , and more preferably between 100 and 600 microns . according to a particularly advantageous arrangement of the invention concerning the case where the drug form comprises microparticles for modified release of api , the overcoating for protection of said microparticles is designed in such a way that it makes it possible , in the event of crushing , to maintain a non - immediate release for at least a part of said microparticles for modified release . advantageously , the protective overcoating represents , for example , between 1 % and 60 %, preferably between 10 % and 60 % by weight of the total mass of the microparticles containing the api . described hereinafter is a preferred embodiment of the drug form according to the invention , in which the overcoating for protection of the microparticles of api comprises : ( i ) at least one film - forming compound which ensures the cohesion of the overcoating and at least one of the following three compounds : the film - forming compound ( i ) has the role of ensuring the cohesion of the overcoating . the film - forming compound ( i ) is , for example , chosen from : the lubricant / caking agent ( ii ) is selected such that , under shear , it is capable of converting the solid drug form into a system on which the crushing has no or little hold . the lubricant / caking agent ( ii ) is preferably chosen from the group comprising : stearic acid and stearates , preferably calcium stearate , zinc stearate or magnesium stearate ; magnesium oxide ; poloxamers ; sodium benzoate ; anionic , cationic or nonionic surfactants ; starches , preferably corn starch ; talc ; colloidal silica ; waxes , preferably hydrogenated plant oils , and even more preferably hydrogenated cotton seed oils , hydrogenated soybean oils , hydrogenated palm oils , hydrogenated castor oils ; glyceryl behenates , tristearins , tripalmitins , trimyristins , yellow waxes , hard fats , anhydrous dairy fats , lanolins , glyceryl palmitostearates , glyceryl stearates , lauric acid macrogol glycerides , cetyl alcohols , glyceryl diisostearates , diethylene glycol monostearates , ethylene monostearates , omegas 3 , and mixtures thereof ; fatty bases for suppositories comprising glycerol , triglycerides , theobroma oils , cocoa butters and mixtures thereof ; and mixtures thereof . the role of the lubricant / caking agent ( ii ) is to greatly limit , or even eliminate , the abrasion of the microparticles containing the api when they are mechanically crushed . the lubricant ( or slip agent )/ caking agent ( ii ) makes it difficult to crush the multiparticulate drug form by facilitating its flow , thus reducing the shear stress applied to the product . the advantage of the lubricant ( or slip agent )/ caking agent ( ii ) to generate wall slip ; the product does not therefore adhere to the wall of the mill , thereby preventing transmission of the shear stress to the active ingredient present in the microparticles . the role of the viscoelastic agent ( iii ) is to dissipate the mechanical shear energy in order to protect the microparticles of api . this viscoelastic agent ( iii ) is , for example , selected from the group of following products : poly - n - vinylamides , gum bases , fatty alcohols , poly - n - vinyllactams , polyvinyl alcohols ( pvas ), polyoxyethylenes ( poes ), polyethylene glycols ( pegs ), polydextroses , hydrogenated mono -, di - and polysaccharides , polyvinylpyrrolidones ( pvps ) ( the latter being preferred ), and mixtures thereof . the role of the plasticizer ( iv ) is to increase the breaking strength of the overcoating . the plasticizer ( iv ) is preferably selected from the group of following products : glycerol and its esters , preferably from the following subgroup : acetylated glycerides , glyceryl monostearate , glyceryl triacetate , glyceryl tributyrate , phthalates , preferably from the following subgroup : dibutyl phthalate , diethyl phthalate , dimethyl phthalate , dioctyl phthalate , citrates , preferably from the following subgroup , acetyl tributyl citrate , acetyl triethyl citrate , tributyl citrate , triethyl citrate , sebacates , preferably from the following subgroup : diethyl sebacate , dibutyl sebacate , adipates , azelates , benzoates , plant oils , preferably cottonseed oils , soybean oils , palm oils , castor oils , and mixtures thereof ; fumarates , preferably diethyl fumarate , malates , preferably diethyl malate , oxalates , preferably diethyl oxalate , succinates , preferably dibutyl succinate , butyrates , cetyl alcohol esters , triacetin , malonates , preferably diethyl malonate , and mixtures thereof . according to a variant , the excipients included in the anti - crushing means ( a ) can be chosen from compression agents , and / or inert microbeads , and / or gum bases , and / or viscoelastic agents such as the viscoelastic agents ( iii ) defined above . the inert microbeads are advantageously insoluble in an aqueous or aqueous - alcoholic medium and are uncompressible . these neutral beads support part of the crushing stresses , thus protecting the microparticles containing the api . they therefore render attempts at mechanical crushing ineffective . in order to prevent the other prerequisite from misuse , namely the liquid extraction of the api , it is proposed , in accordance with an embodiment of the invention , to use , in the drug form , means ( b ) which make it possible to increase the viscosity of the liquid beyond 100 , preferably 200 , and even more preferably beyond 500 mpa · s , and even better still 1000 mpa · s . preferably , the means ( b ) provided for preventing the misuse of the api after a possible liquid extraction comprise “ viscosity - modifying ” excipients capable of increasing the viscosity of the extraction liquid so as to act against the misuse , in particular by injection . advantageously , the “ viscosity - modifying ” excipients capable of increasing the viscosity of the extraction liquid so as to act against the misuse , in particular by injection , are present : in and / or on microparticles , and / or in an overcoating of all or part of the microparticles of api , and / or in the free state , i . e . not contained in nor carried by microparticles . according to a preferred method , the “ viscosity - modifying ” excipients are capable of increasing the viscosity of the liquid used for the possible extraction according to kinetics similar to the kinetics of extraction of the api contained in the microparticles , so as to trap the extracted api in the viscous medium . it is also to the applicant &# 39 ; s credit to propose viscosity - modifying means ( b ) which are effective both in the case of an extraction in an aqueous phase or an extraction in an organic solvent . for the purpose of the invention , the expression “ similar kinetics ” means that the kinetics of the increase in viscosity induced by the means ( b ) is , for example , substantially equal to 0 . 2 - 5 times , preferably to 0 . 3 - 3 times , and even more preferably to 0 . 3 - 2 times the kinetics of extraction of the api contained in the microparticles . in fact : if the increase in viscosity is too rapid , it is possible to extract the microparticles of api which are still loaded ; if , on the other hand , the viscosity modification is too slow , it is possible to release the api into the liquid phase and to recover it before the viscosity modification has taken place . thus , the excipients included in the means ( b ) are preferably chosen from the groups of following polymers : polyacrylic acids and their derivatives , and / or polyoxyethylenes ( poes ), and / or polyvinyl alcohols ( pvas ), polyvinylpyrrolidones ( pvps ), and / or gelatins , and / or cellulose derivatives ( e . g . hydroxypropylmethyl - cellulose , methylcellulose , hydroxyethylcellulose , carboxymethylcellulose ), and / or polysaccharides , preferably from the subgroup comprising : sodium alginate , pectins , guars , xanthans , carragheenans , gellans , and mixtures thereof . advantageously , the excipients constituting the means ( b ) are mixtures of hydrophilic compounds and of hydrophobic compounds , so as to ensure a high viscosity ( greater than 100 mpa · s , for example ) of the extraction liquid , irrespective of whether it is aqueous or organic . preferably , the viscosity - modifying means ( b ) are in the form of microparticles . even more preferably , these viscosity - modifying means ( b ) microparticles are physically indiscernible from the microparticles of api , in order to prevent them being sorted by an appropriate physical means . the microparticles comprising viscosity - modifying means ( b ) are indiscernible from the microparticles of api , in particular because they are the same size and / or of the same density and / or of the same shape and / or of the same color . as regards the amount of viscosity - modifying excipients included in the means ( b ), it can be readily determined by those skilled in the art . this amount corresponds to the minimum amount required to modify the viscosity of 10 ml of extraction liquid to a value greater than or equal to 100 mpa · s . according to another notable embodiment of the invention , the drug form comprises : a . microparticles of api comprising means ( a ), b . and microparticles of viscosity - modifying excipients included in the means ( b ). the proportions a - b can be determined by those skilled in the art according to the desired therapeutic dose . the microparticles containing the api can be microparticles for modified release of api , i . e . microparticles coated with a polymer film deposited according to the techniques known to those skilled in the art . on this question , the article “ formes pharmaceutiques nouvelles ” [ new pharmaceutical forms ] by buri , puisieux , doelker and benoit , lavoisier 1985 , p 175 - 227 , will for example by consulted . by way of examples of microparticles for modified release of api , mention may be made of those described in the following patent documents : ep - b - 0 709 087 and wo - a - 03 / 030878 . according to a first variant , the drug form according to the invention cannot be converted into a dry form which can be administered by nasal aspiration . according to a second variant , the drug form according to the invention cannot be converted into an injectable form . according to a third variant , the drug form according to the invention comprises immediate - release api and / or modified - release api . according to a fourth variant , in the drug form according to the invention , extraction of the api by chewing and / or crushing is not effective . naturally , any combination of at least two of these four variants is included in the present invention . preferably , as regards a drug form comprising at least one apia , said form makes it possible to obtain , after taking one dose , a plasma profile defined as follows : c18h representing the plasma concentration of apia , 18h after taking the dose , c18h * representing the plasma concentration of apia obtained under the same conditions as c18h , with a reference immediate - release oral pharmaceutical form , containing the same dose of apia , cmax representing the maximum plasma concentration of apia after taking the dose , cmax * representing the maximum plasma concentration of apia obtained under the same conditions as cmax , with a reference immediate - release oral pharmaceutical form , containing the same dose of apia . preferably , this drug form comprising an apia is designed in such a way that it , and in particular the coating of the microcapsules , results in a decrease in the inter - and / or intraindividual standard deviation of the cmax , when it is administered orally to a sample of individuals , whatever the fed state or fasting state of the individuals , compared with a pharmaceutical form for immediate release of apia administered to this same sample of individuals , at the same dose , which makes it possible to ensure a smaller variability in effectiveness and in therapeutic safety of the pharmaceutical form . one of the characteristics of the drug form according to the invention is thus defined through a reference clinical test in which the form is administered orally to a sample of human individuals , under experimental conditions which may , for example , be as follows : administration of the form ( gel capsule or tablet or suspension ) once a day , at a given dose , after breakfast , to 20 normal volunteers in the course of a crossover trial study . the plasma concentrations of apia are measured at times : 0 - 0 . 25 - 0 . 5 - 0 . 75 - 1 - 1 . 5 - 2 - 3 - 4 - 6 - 8 - 10 - 12 - 16 - 18 - 20 - 24 - 36 - 48 hours post - administration . this clinical test defines the invention in terms of the pharmacokinetics properties obtained specifically under the conditions of the test . nevertheless , the invention is not limited to an implementation under the conditions of this reference clinical test . the factor f of decrease in the inter - and / or intraindividual standard deviation of the cmax is defined as being the ratio of the inter - and / or intraindividual standard deviation of the cmax of the reference immediate - release pharmaceutical form , to the inter - and intraindividual standard deviation of the cmax of the pharmaceutical form according to the invention , administered at the same dose of apia . advantageously , the factor ( f ) of decrease in the inter - and / or intraindividual standard deviation of the cmax is defined as follows : f ≧ 1 . 05 ; preferably , f ≧ 1 . 5 , and even more preferably , f is between 2 . 0 and 20 . for the purpose of the present invention , the mean peak / trough modulation — ptm — of the plasma profile of an api is defined in the following way : on each of the individual plasma profiles , the individual maximum concentration cmax ′ and the concentration ct ′ are measured , t hours after a single oral administration . the ptm is the arithmetic mean of the cmax ′/ ct ′ individual ratios . for a product intended to be administered daily to the patient , t is 24 hours after the single administration . if the concentration ct ′ ( t = 24 h ) is below the limit of detection of the assay method used and below the limited detection of the method recommended by the pharmacopeia of the united states of america and / or known to those skilled in the art , the concentration c24 ′ used to calculate the ptm will be replaced with the concentration cx ′ measured x hours after oral administration , x being the most belated hour at which it is possible to measure a concentration above the limit of detection of the method used . in this case , x is less than 24 hours after single administration . for example , x is equal to 18 h , or , failing this , 12 h . for a product intended to be administered twice daily to the patient , t is 12 hours in single administration . here also , if the concentration ct ′ ( r = 12 h ) is below the limit of detection of the assay method used and below the limit of detection of the method recommended by the pharmacopeia of the united states of america and / or known to those skilled in the art , the concentration c12 ′ used to calculate the ptm will be replaced with the concentration cx ′ measured x hours after oral administration , x being the most belated hour at which it is possible to measure a concentration above the limit of detection of the method used . in this case , x is less than 12 hours after single administration . the drug form according to the invention is designed in such a way that it results , when it is administered orally to a sample of individuals , in a mean peak / trough modulation of the plasma profiles of the apia less than or equal to the mean peak / trough modulation of the apia of the same sample of individuals having received the same dose of a form for immediate release of apia . for the purpose of the invention , the reduction in the peak / trough modulation of the plasma concentration profiles is given , for example , by the peak / trough modulation decrease factor g . the factor g is defined by the ratio of the peak / trough modulation of the reference immediate - release form to the peak / trough modulation of the form involved in the use according to the invention . preferably , the peak / trough modulation decrease factor g is such that : g ≧ 1 . 05 ; preferably , g ≧ 1 . 5 , and more preferably , g is between 2 . 5 and 20 . in accordance with the use according to the invention , the coating or the matrix of the pharmaceutical form is designed in such a way that the oral administration of this form , to a sample of individuals , results in a variability of the peak / trough modulation of the plasma profiles of the api which is less than the variability of the peak / trough modulation of the api of the same sample of individuals having received the same dose of a form for immediate release of api . for the purpose of the invention , the reduction in the variability of the peak / trough modulation of the plasma concentration profiles is given , for example , by the factor g ′ for decrease in the standard deviation of the peak / trough modulation . the factor g ′ is defined by the ratio of the standard deviation of the peak / trough modulation of the reference immediate - release form to the standard deviation of the peak / trough modulation of the form involved in the use according to the invention . preferably , the factor g ′ for decrease in the standard deviation of the peak / trough modulation is such that : g ′≧ 1 . 1 ; preferably , g ′≧ 1 . 5 , and even more preferably , g ′ is between 2 . 5 and 20 . this drug form for modified release of apia is also designed in such a way that the microcapsules , whilst ingested , are dispersed and individualized when they reach the stomach , which guarantees regular and gradual gastric emptying of the microunits , in the fed state just as in the fasting state , and therefore , ultimately release of the apia within its gastrointestinal window of bioabsorption . for the purpose of the invention , the term “ dose ” denotes the amount of apia contained in the drug form administered orally ; the term “ immediate release ” denotes , in the present disclosure , the release , by an immediate - release form ( irf ), of most of the amount of apia in a relatively brief period of time , for example : at least 70 % of the apia is released in vivo in one hour , preferably in thirty minutes , after oral ingestion ; or at least 70 % of the apia is released in one hour , preferably in thirty minutes , at any ph between 1 . 4 and 6 . 8 in an in vitro dissolution test . all the dissolution profiles to which reference is made in the present disclosure are realized according to the indications of the european pharmacopoeia , 4 th edition , entitled : “ dissolution test for solid oral forms ”: type ii dissolutest carried out under sink conditions at 37 ° c . and with stirring at 100 rpm . in the present disclosure , the term “ modified release ” denotes the release of apia by an oral pharmaceutical formulation , occurring in vivo at a rate less than that of a reference “ immediate - release formulation ”, irf *. such a modified - release formulation can , for example , comprise an immediate - release phase and a slow - release phase . modified - release formulations are well known this field ; see , for example , remington : the science and practice of pharmacy , 19 th edition , mack publishing co . pennsylvania , usa . the modified release can in particular be a sustained and / or controlled , or even delayed , release . the pharmacokinetic parameters to which reference is made in the present invention are defined in the following way . after oral administration of the pharmaceutical form to a sample of n human individuals , the individual plasma concentration profile is measured in each of the patients , from which the individual pharmacokinetic parameters are drawn : tmax , cmax , c18h : tmax is the amount of time after which the plasma concentration reaches its maximum , cmax . c18h is the plasma concentration 18 hours after administration . based on these individual parameters , those skilled in the art conventionally calculate the mean values of these parameters and their standard deviations . further details on the discussion of these parameters will be found in the work : pharmacokinetics and pharmacodynamic data analysis 3 rd ed ., j . gabrelsson et al ., kristianstads bocktryckeri ab , sweden , 2000 . the comparison of the parameters c18h and c18h *, and cmax and cmax * is carried out in a statistically significant manner , under the same conditions and at the same dose of apia . the peak / trough modulation of the plasma concentration profiles is defined by the mean of the cmax / c18h ratio for the apia . the expression “ dispersed and individualized ” means that the apia - based microcapsules are not trapped in a matrix when they reach the stomach just after they have been ingested . the microcapsules become disseminated in the stomach after they have entered the latter . advantageously , the drug form according to the invention comprises microgranules for immediate release of apia . the secondary advantages of the invention are in particular as follows : this oral pharmaceutical form of apia , which can be administered once or twice a day , is such that , once ingested , the apia that it contains is released in the gastrointestinal tract and bioabsorbed within its absorption window , even if the latter is narrow . this oral pharmaceutical form of apia , which can be administered once or twice a day , guarantees that , once the oral pharmaceutical form has been ingested , the apia that it contains will not pass in front of its bioabsorption window (!!!) without being released . this oral pharmaceutical form of apia , which can be administered once or twice a day , guarantees that , once the oral pharmaceutical form has been ingested , the apia that it contains will be released independently of the open or closed state of the pylorus . this oral pharmaceutical form of apia , which can be administered once or twice a day , is not subject , or barely subject , to the phenomenon of inter - or intraindividual variability of gastric emptying and , ultimately , of in vivo absorption of apia . this oral pharmaceutical form of apia , which can be administered once or twice a day , is at least as effective as the immediate - release once - a - day forms currently in use . this oral pharmaceutical form of apia , which can be administered once or twice a day and which comprises microcapsules for modified release of apia , draws some of its advantages from the small size (≦ 1000 μm ) of these microcapsules and the large number thereof ( e . g . at least a thousand or so per dose ), which allows gradual and well - controlled gastric emptying . this oral pharmaceutical form of apia , which can be administered once or twice a day , makes it possible to increase the tmax of the apias and also the period of time for which the plasma concentration of apia is greater than the minimum plasma concentration of apia , below which the apia is therapeutically ineffective . this oral pharmaceutical form of apia has an in vitro dissolution profile independent of the dose of apia . this oral pharmaceutical form of apia is composed of microparticles which have the same composition by weight irrespective of the doses of apia . this oral pharmaceutical form of apia , which can be administered once or twice a day , is suitable for patients who have difficulty in swallowing , in particular for children or infants who not only cannot swallow , but who , in addition , require and adjustment of the dose administered according to their weight . this oral pharmaceutical form of apia , which can be administered once or twice a day , offers the possibility of mixing the apia with one or more other active ingredients in the same oral form , it being possible for the respective release times of these various active ingredients to be readily adjusted , independently of one another . this oral pharmaceutical form of apia can exist in various gallenic presentation forms , including in particular : tablet , sachet , oral suspension , gel capsule , etc . the oral gallenic form according to the invention consists of a large number ( for example of the order of about one to several thousand ) of microcapsules ( or microgranules for immediate release of apia , or of a mixture of several types of microcapsules or microgranules ), this multiplicity ensuring , statistically , good reproducibility of the kinetics of transit of the apia throughout the gastrointestinal tract , and , subsequently , good control of bioavailability and better effectiveness . the use of a mixture of microcapsules with different modified release profiles makes it possible to produce release profiles which ensure , by means of suitable regulation of the various fractions , a constant level of plasma concentration of apia . there is less sensitivity to the variability in gastric emptying because the emptying , which takes place over a large number of particles , is statistically more reproducible . the bringing of the tissues into contact with a high dose of apia ( dose dumping ) is prevented . each microcapsule in fact contains only a very small dose of apia . the risk of tissue deterioration due to a local overconcentration of apia is thus done away with . this pharmaceutical form does not induce any degradation of the starting apia and preserves the initial polymorphism of the apia . their size of less than or equal to 1000 μm and also the characteristics of their possible coating allows the microcapsules to increase their transit time in the upper parts of the gastrointestinal tract , which ensures an increase in the amount of time taken for the apia to pass in front of its absorption window and thus maximizes the bioavailability of the apia . in accordance with the first embodiment of the invention , the drug form is characterized in that 70 % of the apia is released between 1 and 24 h , preferably 2 and 15 h , and more preferably 2 and 12 h . advantageously , this drug form is characterized by an in vitro dissolution profile of the oral pharmaceutical form such that , for any value of the time t of between 2 h and t ( 70 %), preferably for any value of time t of between 1 h and t ( 70 %), the percentage of apia dissolved is greater than or equal to 35 t / t ( 70 %). the composition of the coating of the microcapsules according to the first embodiment corresponds , advantageously , to one of the following two families a and b : 1a — at least one film - forming polymer ( p1 ) which is insoluble in the fluids of the tract , present in a proportion of 50 % to 90 %, preferably 50 % to 80 % by weight on a dry basis relative to the total mass of the coating composition , and comprising at least one water - insoluble derivative of cellulose ; 2a — at least one nitrogenous polymer ( p2 ) present in a proportion of 2 % to 25 %, preferably 5 % to 15 % by weight on a dry basis relative to the total mass of the coating composition and consisting of at least one polyacrylamide and / or one poly - n - vinylamide and / or one poly - n vinyllactam ; 3a — at least one plasticizer present in a proportion of 2 % to 20 %, preferably of 4 % to 15 % by weight on a dry basis relative to the total mass of the coating composition and consisting of at least one of the following compounds : glyceryl esters , phthalates , citrates , sebacates , cetyl alcohol esters , castor oil ; 4a — at least one surfactant and / or lubricant , present in a proportion of 2 % to 20 %, preferably of 4 % to 15 % by weight on a dry basis relative to the total mass of the coating composition and chosen from anionic surfactants and / or from nonionic surfactants and / or from lubricants ; it being possible for said surfactant and / or lubricant to comprise just one or a mixture of the abovementioned products ; 1b — at least one film - forming polymer which is insoluble in the fluids of the gastrointestinal tract , 2b — at least one water - soluble polymer , 3b — at least one plasticizer , 4b and , optionally , at least one surfactant / lubricant , preferably consisting of at least one anionic surfactant and / or at least one nonionic surfactant . according to a preferred mode of the invention , the families a and b from which the constituents of the coating composition are chosen are as follows : 1a — ethylcellulose and / or cellulose acetate ; 2a — polyacrylamide and / or polyvinylpyrrolidone ; 3a — castor oil ; 4a — alkali metal or alkaline earth metal salt of fatty acids , stearic acid and / or oleic acid being preferred , a polyoxyethylenated sorbitan ester , derivatives of polyoxyethylenated castor oil , a stearate , preferably calcium stearate , magnesium stearate , aluminum stearate or zinc stearate , a stearyl fumarate , preferably sodium stearyl fumarate , glyceryl behenate ; taken on their own or as a mixture with one another ; water - insoluble derivatives of cellulose , ethylcellulose and / or cellulose acetate being particularly preferred , water - insoluble acrylic polymers , polyvinyl acetates , and mixtures thereof ; water - soluble derivatives of cellulose , polyacrylamides , poly - n - vinylamides , poly - n - vinyllactams , polyvinyl alcohols ( pvas ), polyoxyethylenes ( poes ), polyvinylpyrrolidones ( pvps ) ( the latter being preferred ), and mixtures thereof ; glycerol and its esters , preferably from the following subgroup : acetylated glycerides , glyceryl monostearate , glyceryl triacetate , glyceryl tributyrate , phthalates , preferably from the following subgroup : dibutyl phthalate , diethyl phthalate , dimethyl phthalate , dioctyl phthalate , citrates , preferably from the following subgroup : acetyl tributyl citrate , acetyl triethyl citrate , tributyl citrate , triethyl citrate , sebacates , preferably from the following subgroup : diethyl sebacate , dibutyl sebacate , adipates , azelates , benzoates , plant oils , fumarates , preferably diethyl fumarate , malates , preferably diethyl malate , oxalates , preferably diethyl oxalate , succinates , preferably dibutyl succinate , butyrates , cetyl alcohol esters , salicylic acid , triacetin , malonates , preferably diethyl malonate , castor oil ( the latter being particularly preferred ), and mixtures thereof ; alkali metal or alkaline earth metal salts of fatty acids , stearic acid and / or oleic acid being preferred , polyoxyethylenated oils , preferably polyoxyethylenated hydrogenated castor oil , polyoxyethylene - polyoxypropylene copolymers , polyoxyethylenated sorbitan esters , polyoxyethylenated castor oil derivatives , stearates , preferably calcium stearate , magnesium stearate , aluminum stearate or zinc stearate , stearyl fumarates , preferably sodium stearyl fumarate , glyceryl behenate , and mixtures thereof . preferably , the film coating consists of a single layer , the mass of which represents from 1 % to 50 % by weight , preferably from 5 % to 40 % by weight , of the total mass of the microcapsules . other details and examples of compositions and of methods for obtaining the microcapsules according to the first embodiment according to the invention are given in wo - a - 03 / 084518 , the content of which is , integrated into the present disclosure by way of reference . for further details in qualitative and quantitative terms , as regards the coating composition of family a , reference will be made to european patent ep - b - 0 709 087 , the content of which is integrated into the present disclosure by way of reference . in accordance with a second embodiment of the invention , the oral drug form is such that : the release of apia is controlled by two distinct triggering mechanisms , one being based on a variation in ph and the other allowing the release of apia after a predetermined residence time in the stomach ; at constant ph 1 . 4 , the dissolution profile contains a lag phase which lasts less than or equal to 7 hours , preferably less than or equal to 5 hours , and even more preferably between 1 and 5 hours , and the passing from ph 1 . 4 to ph 7 . 0 results in a release phase which begins without any lag time . in accordance with the second embodiment of the invention , the pharmaceutical form has an in vitro dissolution profile which may be as indicated below : at least 20 % of the apia is released after 2 hours at ph = 1 . 4 ; at least 50 % of the apia is released after 16 hours at ph = 1 . 4 . advantageously , the microcapsules for modified release of apia , according to the second embodiment of the invention , have the following specificities : the coating allowing the modified release of apia comprises a composite material at least one hydrophilic polymer i bearing groups which are ionized at neutral ph , at least one hydrophobic compound ii ; representing a mass fraction (% by weight relative to the total mass of the microcapsules ) ≦ 40 ; and their mean diameter is less than 2000 μm , and preferably between 50 and 800 μm , and even more preferably between 100 and 600 μm . according to another advantageous characteristic , the composite material i - ii of the coating allowing the modified release of apia is such that : the weight ratio ii / i is between 0 . 2 and 1 . 5 , preferably between 0 . 5 and 1 . 0 , and the hydrophobic compound ii is selected from products which are crystalline in the solid state and which have a melting point tmii ≧ 40 ° c ., preferably tmii ≧ 50 ° c ., and even more preferably 40 ° c .≦ tmii ≦ 90 ° c . according to an embodiment of predilection , the hydrophilic polymer i is chosen from : i . a copolymers of ( meth ) acrylic acid and of an alkyl ester of ( meth ) acrylic acid , and mixtures thereof ; i . b cellulose derivatives , preferably cellulose acetates , cellulose phthalates , cellulose succinates , and mixtures thereof , and even more preferably hydroxypropylmethylcellulose phthalates , hydroxyl - propylmethylcellulose acetates , hydroxypropylmethyl - cellulose succinates , and mixtures thereof ; and mixtures thereof . the polymers i which are even more preferred are copolymers of ( meth ) acrylic acid and of alkyl ( e . g . c 1 - c 6 alkyl ) esters of ( meth ) acrylic acid . these copolymers are , for example , of the type such as those sold by the company röhm pharma polymers under the registered trade marks eudragit ®, of the l and s series ( such as , for example , eudragit ® l100 , s100 , l30 d - 55 and l100 - 55 ). these copolymers are anionic enteric copolymers which are soluble in an aqueous medium at phs greater than those encountered in the stomach . still according to the embodiment of the predilection , the compound ii is chosen from the group of following products : ii . a — plant waxes taken on their own or as mixtures with one another ; ii . b — hydrogenated plant oils taken on their own or as mixtures with one another ; ii . c — mono - and / or di - and / or trimesters of glycerol and of at least one fatty acid ; ii . d — mixtures of monoesters , of diesters and of triesters of glycerol and of at least one fatty acid ; ii . e — and mixtures thereof . even more preferably , the compound ii is chosen from the group of following products : hydrogenated cottonseed oil , hydrogenated soybean oil , hydrogenated palm oil , glyceryl behenate , hydrogenated castor oil , tristearin , tripalmitin , trimyristin , yellow wax , hard fat or fat useful as suppository bases , anhydrous dairy fats , lanolin , glyceryl palmitostearate , glyceryl stearate , lauryl macrogol glycerides , cetyl alcohol , polyglyceryl diisostearate , diethylene glycol monostearate , ethylene glycol monostearate , omega - 3 , and any mixture with one another , preferably from the subgroup of following products : hydrogenated cottonseed oil , hydrogenated soybean oil , hydrogenated palm oil , glyceryl behenate , hydrogenated castor oil , tristearin , tripalmitin , trimyristin , and any mixture with one another . in practice , and without this being limiting , the compound ii is preferably chosen : from the group of products sold under the following trade marks : dynasan ®, cutina ®, hydrobase ®, dub ®, castorwax ®, croduret ®, compritol ®, sterotex ®, lubritab ®, apifil ®, akofine ®, softtisan ®, hydrocote ®, livopol ®, super hartolan ®, mgla ®, corona ®, protalan ®, akosoft ®, akosol ®, cremao ®, massupol ®, novata ®, suppocire ®, wecobee ®, witepsol ®, lanolin ®, incromega ®, estaram ®, suppoweiss ®, gelucire ®, precirol ®, emulcire ®, plurol diisostéarique ®, geleol ®, hydrine ®, monthyle ®, and mixtures thereof ; and also from the group of additives for which the codes are as follows : e 901 , e 907 , e 903 , and mixtures thereof ; and , preferably , from the group of products sold under the following trademarks : dynasan ® p60 , dynasan ® 114 , dynasan ® 116 , dynasan ® 118 , cutina ® hr , hydrobase ® 66 - 68 , dub ® hph , compritol ® 888 , sterotex ® nf , sterotex ® k , lubritab ®, and mixtures thereof . according to another advantageous characteristic of the invention , the coating allowing the modified release of apia is free of talc . advantageously , the coating of the microcapsules can comprise , in addition to the essential constituents i and ii , other conventional ingredients known to those skilled in the art , such as , in particular : colorants , plasticizers , such as , for example , dibutyl sebacate , hydrophilic compounds , such as , for example , cellulose and its derivatives or polyvinylpyrrolidone and its derivatives , and mixtures thereof . without it being limiting and according to an even more preferred embodiment , the coating of the microcapsules for modified release of apia comprises a single composite i - ii film coating . other details and examples of compositions and of methods for obtaining the microcapsules according to the second embodiment according to the invention are given in wo - a - 03 / 030878 , the content of which is integrated into the present disclosure by way of reference . in quantitative terms , the monolayer of coating can represent , for example , at most 40 %, preferably at most 30 % by weight of the microcapsules . such a limited degree of coating makes it possible to produce gallenic units which each contain a high dose of active ingredient , without exceeding a size which is completely unacceptable with regard to swallowing . the observance and therefore the success of the treatment can only be improved by this . according to a third embodiment of the invention , the oral pharmaceutical form according to the invention comprises at least two populations of microcapsules for modified release of apia . each population of microcapsules for modified release of apia can be in accordance with the first or with the second embodiment of the invention . according to a variant - 2i - of the second embodiment of the invention combined with the third embodiment , the oral pharmaceutical form according to the invention comprises at least two populations of microcapsules having different dissolution profiles , for at least one ph value of between 1 . 4 and 7 . 4 . according to a variant - 2ii - of the second embodiment of the invention combined with the third embodiment , the oral pharmaceutical form according to the invention comprises at least two populations of microcapsules for modified release of apia which differ by virtue of their respective triggering phs . according to yet another variant - 2iii - of the second embodiment of the invention combined with the third embodiment , the oral pharmaceutical form according to the invention comprises at least two populations of microcapsules for modified release of apia which differ by virtue of their respective triggering times . according to a fourth embodiment of the invention , the oral pharmaceutical form according to the invention comprises at least one population of microcapsules for modified release of apia and at least one population of microgranules for immediate release of apia . according to a variant - 2iv - of the second embodiment of the invention combined with the fourth embodiment , the oral pharmaceutical form according to the invention comprises : at least one population of microgranules for immediate release of apia ; at least one population p1 of microcapsules for modified release of apia , and at least one population p2 of microcapsules for modified release of apia ; and , moreover , the respective triggering phs of p1 and of p2 differ by at least 0 . 5 ph unit , preferably by at least 0 . 8 ph unit , and even more preferably by at least 0 . 9 ph unit . advantageously , the respective triggering phs of the various populations of microcapsules for modified release of apia are between 5 and 7 . according to a variant - 2v - of the second embodiment of the invention combined with the fourth embodiment , the oral pharmaceutical form according to the invention comprises : at least one population of microgranules for immediate release of apia ; at least one population p1 ′ of microcapsules for modified release of apia , the triggering ph of which is equal to 5 . 5 ; and at least one population p2 ′ of microcapsules for modified release of apia , the triggering ph of which is between 6 . 0 inclusive and 6 . 5 inclusive . the populations p1 , p2 , p1 ′ and p2 ′ of the variants - 2iv - and - 2v - of the 2 nd embodiment comprise microcapsules for modified release of apia , obtained in accordance with the 2 nd embodiment of the invention . to illustrate the variants according to which microgranules for immediate release of apia are present in the pharmaceutical form according to the invention , it can be specified that these variants can correspond to cases where this pharmaceutical form comprises , for example , at least one population of microgranules for immediate release of apia , the behavior of which in an in vitro dissolution test is such that at least 80 % of apia is released in 1 hour at any ph between 1 . 4 and 7 . 4 . the drug form according to the invention can comprise , in addition to the microunits consisting of the microcapsules for modified release of apia , microunits of apia other than microcapsules , i . e . microgranules for immediate release of apia and / or of ( an ) other active ingredient ( s ) api ( s ). these immediate - release microgranules are advantageously uncoated and can be of the same type as those used in the preparation of the microcapsules according to the invention . in addition , all the microunits ( microcapsules and , optionally , microgranules ) constituting the medicament according to the invention can be formed by various populations of microunits , these populations differing from one another at least by virtue of the nature of the active ingredient ( s ) other than the apia contained in these microunits and / or by virtue of the amount of apia or of other optional active ingredient ( s ) that they contain and / or by virtue of the composition of the coating and / or by virtue of the fact that they are modified - release or immediate release . according to a specific embodiment , the drug form according to the invention is in the form of single oral daily dose comprising from 1000 to 500 000 microunits containing apia . according to another specific embodiment , the drug form according to the invention is in the form of a single oral daily dose comprising from 1000 to 500 000 microcapsules for modified release of apia . according to a variant , the drug form according to the invention comprises at least one suspension of microcapsules of apia in an aqueous liquid phase which is preferably saturated or which becomes saturated with apia on contact with the microcapsules , the coating of said microcapsules preferably having a composition corresponding to one of the following two families a ′ and b ′: 1a ′— at least one film - forming polymer ( p1 ) which is insoluble in the fluids of the tract , present in a proportion of 50 % to 90 %, preferably 50 % to 80 % by weight on a dry basis relative to the total mass of the coating composition , and comprising at least one water - insoluble derivative of cellulose ; 2a ′— at least one nitrogenous polymer ( p2 ) present in a proportion of 2 % to 25 %, preferably 5 % to 15 % by weight on a dry basis relative to the total mass of the coating composition and consisting of at least one polyacrylamide and / or one poly - n - vinylamide and / or one poly - n - vinyllactam ; 3a ′— at least one plasticizer present in a proportion of 2 % to 20 %, preferably of 4 % to 15 % by weight on a dry basis relative to the total mass of the coating composition and consisting of at least one of the following compounds : glyceryl esters , phthalates , citrates , sebacates , cetyl alcohol esters , castor oil ; 4a ′— at least one surfactant and / or lubricant , present in a proportion of 2 % to 20 %, preferably of 4 % to 15 % by weight on a dry basis relative to the total mass of the coating composition and chosen from anionic surfactants and / or from nonionic surfactants and / or from lubricants ; it being possible for said surfactant and / or lubricant to comprise just one or a mixture of the abovementioned products ; 1b ′— at least one film - forming polymer which is insoluble in the fluids of the gastrointestinal tract , 2b ′— at least one water - soluble polymer , 3b ′— at least one plasticizer , 4b ′— and , optionally , at least one surfactant / lubricant , preferably selected from the group of following products : in practice , the coating composition families a ′ and b ′ are , for example , as follows : 1a ′— ethylcellulose and / or cellulose acetate ; 2a ′— polyacrylamide and / or polyvinylpyrrolidone ; 3a ′— castor oil ; 4a ′— alkali metal or alkaline earth metal salt of fatty acids , stearic acid and / or oleic acid being preferred , polyoxyethylenated sorbitan esters , derivatives of polyoxyethylenated castor oil , stearates , preferably calcium stearate , magnesium stearate , aluminum stearate or zinc stearate , stearyl fumarate , preferably sodium stearyl fumarate , glyceryl behenate ; taken alone or as a mixture with one another ; water - insoluble derivatives of cellulose , ethylcellulose and / or cellulose acetate being particularly preferred , acrylic polymers , polyvinyl acetates , and mixtures thereof ; water - soluble derivatives of cellulose , polyacrylamides , poly - n - vinylamides , poly - n - vinyllactams , polyvinyl alcohols ( pvas ), polyoxyethylenes ( poes ), polyvinylpyrrolidones ( pvps ) ( the latter being preferred ), and mixtures thereof ; glycerol and its esters , preferably from the following subgroup : acetylated glycerides , glyceryl monostearate , glyceryl triacetate , glyceryl tributyrate , phthalates , preferably from the following subgroup : dibutyl phthalate , diethyl phthalate , dimethyl phthalate , dioctyl phthalate , citrates , preferably from the following subgroup : acetyl tributyl citrate , acetyl triethyl citrate , tributyl citrate , triethyl , citrate , sebacates , preferably from the following subgroup : diethyl sebacate , dibutyl sebacate , adipates , azelates , benzoates , plant oils , fumarates , preferably diethyl fumarate , malates , preferably diethyl malate , oxalates , preferably diethyl oxalate , succinates , preferably dibutyl succinate , butyrates , cetyl alcohol esters , salicylic acid , triacetin , malonates , preferably diethyl malonate , castor oil ( the latter being particularly preferred ), and mixtures thereof ; alkali metal or alkaline earth metal salts of fatty acids , stearic acid and / or oleic acid being preferred , polyoxyethylenated oils , preferably polyoxy - ethylenated hydrogenated castor oil , polyoxyethylene - polyoxypropylene copolymers , polyoxyethylenated sorbitan esters , polyoxyethylenated castor oil derivatives , stearates , preferably calcium stearate , magnesium stearate , aluminum stearate or zinc stearate , stearyl fumarates , preferably sodium stearyl fumarate , glyceryl behenate , and mixtures thereof . according to an advantageous mode of this variant , in which the drug form is in suspension , it is envisaged that this suspension comprises means ( b ) containing “ viscosity - modifying ” excipients , which are in the form of coated particles , each coated with at least one hydrophobic film - coating . this hydrophobic film - coating comprises , for example , at least one product chosen from the group comprising polymers which are insoluble in the fluids of the tract . this variant makes it possible , during a normal use , for these viscosity - modifying agents to remain encapsulated and therefore inactive . in the event of misuse involving crushing , the hydrophobic film - coating of these viscosity - modifying agents cracks , and the latter are then released and can perform their function , leading to a significant increase in viscosity , putting a stop to any misuse by injection . advantageously , the coating for coating ( controlling the diffusion of the apia ) of the microcapsules of the suspension consists of a single layer . 30 % to 90 % by weight , preferably 60 % to 85 % by weight of liquid phase ( advantageously of aqueous solution ), 5 % to 70 % by weight , preferably 15 % to 40 % by weight of microcapsules . in practice , the amount of apia solvent liquid phase ( preferably aqueous solution ) is preferably such that the proportion of apia dissolved and originating from the microcapsules is less than or equal to 15 %, preferably less than or equal to 5 % by weight relative to the total mass of apia contained in the microcapsules . preferably , the liquid phase is at least partly , preferably completely , saturated with apia subsequent to the incorporation of the microcapsules into this liquid phase . an alternative for this suspension is for the saturation with apia to take place by means of the apia contained in the microcapsules . another alternative for this suspension is for the liquid phase to be at least partly , preferably completely , saturated with apia by means of nonencapsulated apia . another alternative for this suspension is that it is in the form of a powder for oral suspension to be reconstituted : the powder contains all the elements of the suspension described above , except the water ( or the liquid phase ), which is added by the user . besides the liquid forms , the drug form according to the invention can be in the form of a sachet of microcapsule powder , of a tablet obtained from microcapsules , or of a gel capsule containing microcapsules . according to another of its aspects , the invention also encompasses the use of the microcapsules for modified release of apia as defined above , and optionally of the microgranules for immediate release of apia as defined above , for the preparation of pharmaceutical , microparticulate oral galenic forms , preferably in the form of tablets , advantageously orodispersible tablets , of powders , of gel capsules or of suspensions . according to yet another of its aspects , the invention also encompasses the use of the microcapsules for modified release of apia as defined above , and optionally of the microgranules for immediate release of apia as defined above , for the preparation of a therapeutically safe , microparticulate oral pharmaceutical form designed in such a way that , once said pharmaceutical form has been ingested , the microcapsules that it contains are dispersed and individualized when they reach the stomach , which allows these microcapsules to be subjected to regular and gradual gastric emptying , whether the patient had eaten or was fasting at the time the dose was taken , thus guaranteeing a release of apia within its window of bioabsorption . the apia used belongs , for example , to at least one of the following families of active substances : amphetamines , analgesics , anorexigens , antalgics , antidepressants , antiepileptics , antimigraine agents , antiparkinsonian agents , antitussives , anxiolytics , barbiturates , benzodiazepines , hypnotics , laxatives , neuroleptics , opiates , psychostimulants , psychotropic agents , sedatives and stimulants . even more specifically , the apia used is chosen from the following compounds : acetorphine , acetylalpha - methylfentanyl , acetyldihydrocodeine , acetylmethadol , alfentanil , allylprodine , alphacetylmethadol , alphameprodine , alphamethadol , alphamethylfentanyl , alpha - methylthofentanyl , alphaprodine , anileridine , atropine , benzethidine , benzylmorphine , beta - hydroxyfentanyl , beta - hydroxymethyl - 3 - fentanyl , beta - cetylmethadol , betameprodine , betamethadol , betaprodine , bezitramide , buprenorphine , dioxaphetyl butyrate , cannabis , cetobemidone , clonitazene , codeine , coca , cocaine , codoxime , concentrate of poppy straw , desomorphine , dextromoramide , dextropropoxyphene , diampromide , diethylthiambutene , difenoxine , dihydrocodeine , dihydroetorphine , dihydromorphine , dimenoxadol , dimepheptanol , dimethylthiambutene , diphenoxylate , dipipanone , drotebanol , ecgonin , ephedrine , ethylmethylthiambutene , ethylmorphine , etonitazene , etorphine , etoxeridine , fentanyl , furethidine , heroin hydrocodone , hydromorphinol , hydromorphon , hydroxypethidine , isomethadone , levomethorphan , levomoramide , levophenacylmorphan , levorphanol , meperidine , metazocine , methadone , methyldesorphine , methyldihydromorphine , methyl - phenidate , methyl - 3 - thiofentanyl , methyl - 3 - fentanyl , metopon , moramide , morpheridine , morphine , mppp , myrophine , nicocodine , nicodicodine , nicomorphine , noracymethadol , norcodeine , norlevorphanol , normethadone , normorphine , norpipanone , opium , oxycodone , oxymorphone , para - fluorofentanyl , pepap , pentazocine , pethidine , phenampromide , phenazocine , phenomorphan , phenoperidine , pholcodine , piminodine , piritramide , proheptazine , propanolol , properidine , propiram , racemethorphan , racemoramide , racemorphan , remifentanil , sufentanil , thebacone , thebaine , thiofentanyl , tilidine , trimeperidine , and mixtures thereof . advantageously , the apia is selected from opiates , and more particularly from the group comprising the following compounds : anileridine , acetorphine , acetylalpha - methylfentanyl , acetyldihydrocodeine , acetylmethadol , alfentanil , allylprodine , alphacetylmethadol , alphameprodine , alphaprodine , alphamethadol , alphamethylfentanyl , alpha - methylthiofentanyl , alphaprodine , anileridine , atropine , butorphanol , benzethidine , benzylmorphine , beta - hydroxyfentanyl , beta - hydroxymethyl - 3 - fentanyl , betacetylmethadol , betameprodine , betamethadol , betaprodine , bezitramide , buprenorphine , dioxaphetyl butyrate , clonitazene , cyclazocine , cannabis , cetobemidone , clonitazene , codeine , coca , cocaine , codoxime , concentrate of poppy straw , dezocine , dimenoxadol , dioxaphetylbutyrate , dipipanone , desomorphine , dextromoramide , dextropropoxyphene , diampromide , diethylthiambutene , difenoxine , dihydrocodeine , dihydroetorphine , dihydromorphine , dimenoxadol , dimepheptanol , dimethylthiambutene , diphenoxylate , dipipanone , drotebanol , eptazocine , ethoheptazine , ethylmethylthiambutene , ethylmorphine , etonitazene , ecgonin , ephedrine , ethylmethylthiambutene , ethylmorphine , etonitazene , etorphine , etoxeridine , fentanyl , furethidine , heroin , hydrocodone , hydromorphinol , hydromorphone , hydroxypethidine , isomethadone , ketobemidone , levallorphan , iofentanil , levomethorphan , levomoramide , levophenacylmorphan , levorphanol , meptazinol , meperidine , metazocine , methadone , methyldesorphine , methyldihydromorphine , methylphenidate , methyl - 3 - thiofentanyl , methyl - 3 - fentanyl , metopon , moramide , morpheridine , morphine , mppp , myrophine , nalbuphine , narceine , nicomorphine , norlevorphanol , normethadone , nalorphine , normorphine , nicocodine , nicodicodine , nicomorphine , noracymethadol , norcodeine , norlevorphanol , normethadone , normorphine , norpipanone , opium , oxycodone , oxymorphone , papavereturn , phenadoxone , phenoperidine , promedol , properidine , propiram , propoxyphene , para - fluorofentanyl , pepap , pentazocine , pethidine , phenampromide , phenazocine , phenomorphan , phenoperidine , pholcodine , piminodine , piritramide , proheptazine , propanolol , properidine , propiram , racemethorphan , racemoramide , racemorphan , remifentanil , sufentanil , thebacone , thebaine , thiofentanyl , tilidine , trimeperidine , tramodol , pharmaceutically acceptable salts of these compounds and mixtures of these compounds and / or of their salts . the drug forms according to the invention can comprise at least one other active ingredient other than an apia . the abbreviation api will hereinafter denote , without distinction , one or more active ingredients other than an apia . the in vivo or in vitro release of the api can be immediate or modified . the api can be contained in microgranules for immediate release of the api or in microcapsules for modified release of the api . this api can be chosen , inter alia , from the group comprising antidepressants , amphetamines , anorexigens , analgesics , antiepileptics , antimigraine agents , antiparkinsonian agents , antitussives , anxiolytics , barbiturates , benzodiazepines , hypnotics , laxatives , neuroleptics , psychostimulants , psychotropic agents , sedatives , stimulants , anti - inflammatories , pharmaceutically acceptable salts of these compounds and mixtures of these compounds and / or of their salts . by way of examples of anti - inflammatories , mention may , for example , by made of ibuprofen , acetaminophen , diclofenac , naproxene , benoxaprofen , flurbiprofen , fenoprofen , flubufen , ketoprofen , indoprofen , piroprofen , carprofen , oxaprozine , pramoprofen , muroprofen , trioxaprofen , suprofen , aminoprofen , tiaprofenic acid , fluprofen , bucloxic acid , indomethacin , sulindac , tolmetine , zomepirac , tiopinac , zidometacin , acemetacin , fentiazac , clidanac , oxpinac , mefenamic acid , meclofenamic acid , flufenamic acid , niflumic acid , tolfenamic acid , diflurisal , flufenisal , piroxicam , sudoxicam or isoxicam , pharmaceutically acceptable salts of these compounds and mixtures of these compounds and / or of their salts . in accordance with an advantageous mode of the invention , the drug form comprises at least two populations of microcapsules having different , release profiles according to the similarity factor f2 . the nonlimiting examples which follow make it possible to understand the invention more clearly and to reveal its advantages . fig1 represents the dissolution profile in a reference test (% dissolution d as a function of time t ), in vitro , of the microparticles without protective overcoating of example 1 . fig2 represents the dissolution profile in the reference test (% dissolution d as a function of time t ), in vitro , of the microparticles with protective overcoating of example 2 , before crushing . fig3 represents the dissolution profile in the reference test (% dissolution d as a function of time t ), in vitro , of the microparticles with protective overcoating of example 2 , after crushing . fig4 represents the profile for increase in viscosity v in mpa · s as a function of time t in hours , of the microparticles of viscosity - modifying agents for example 3 , placed in the presence of water . fig5 represents the release profiles by weight of apia as a function of time in hours ) of an intact tablet and of the crushed tablet and at ph 1 . 4 . legend : -▪- intact tablet , -□- crushed tablet . fig6 represents the release profiles (% by weight of apia as a function of time in hours ) of the intact and crushed microcapsules at ph 1 . 4 . legend : -▴- anti - misuse microcapsules ; - δ - crushed anti - misuse microcapsules . the reference dissolution test in the examples which follow is an in vitro dissolution test carried out according to the indications of the european pharmacopoiea , 4 th edition , entitled : “ dissolution test for solid oral forms ”: type ii dissolutest carried out under sink conditions , maintained at 37 ° c . and stirred at 100 rpm . in some of the following examples , metformin is used as model active ingredient . metformin hydrochloride has a solubility and a stability comparable to oxycodone hydrochloride . step 1 : granules 45 g of acyclovir , 25 g of peg 40 - hydrogenated castor oil and 30 g of povidone are solubilized beforehand in a water / acetone / isopropanol mixture ( 5 / 57 / 38 m / m ). this solution is then sprayed onto 800 g of cellulose spheres ( of diameter between 100 and 200 μm ) in a glatt gpc - g1 fluidized airbed device . 50 g of granules obtained above are coated with 6 . 5 g of ethylcellulose , 0 . 5 g of castor oil , 0 . 5 g of peg 40 - hydrogenated castor oil ( basf ) and 2 . 5 g of povidone dissolved in an acetone / isopropanol mixture ( 60 / 40 m / m ), in a miniglatt fluidized airbed device . the average diameter of the particles obtained is 180 μm . these microparticles are virtually spherical and release their content over approximately 8 hours in the reference dissolution test ( fig1 ). overcoating of the microparticles of acyclovir in such a way as to minimize their sensitivity to crushing 10 g of ethylcellulose , 25 g of peg 6000 and 5 g of magnesium stearate are dispersed in 160 g of isopropanol . this dispersion is then sprayed onto 40 g of microparticles obtained at the end of the second step of example 1 . in this example , the protective layer ( or overcoating ) does not modify the kinetics of release of api in the reference dissolution test ( fig2 ). when these objects are subjected to shear , for example in a mortar , the layer containing the ethylcellulose , the peg 6000 and the magnesium stearate protects the particle of active ingredient by reducing the shear effects . the release kinetics in the reference dissolution test for the microparticles after crushing remain sustained and virtually identical to the starting microparticles ( fig3 ). 500 g of polyoxyethylene , 80 g of hydroxypropylcellulose and 20 g of ethylcellulose are dispersed in an acetone / isopropanol mixture ( 60 / 40 m / m ). this solution is then sprayed onto 400 g of cellulose spheres ( of diameter of between 100 and 200 μm ) in a glatt gpc - g1 fluidized airbed device . the average diameter of the microparticles obtained is 260 μm . 2 . 5 g of microparticles thus obtained are introduced into 100 g of water . the viscosity at 25 ° c . over time is given in fig4 . at equilibrium , the solution obtained has a viscosity of the order of 3000 mpa · s . a solution this viscous cannot be injected . the kinetics for increasing viscosity are comparable to the release kinetics of the microparticles of api obtained in examples 1 and 2 . the final pharmaceutical form according to the invention is the combination of the microparticles prepared in example 2 and in example 3 . these two types of microparticles are physically indiscernible ( same size , shape , density , etc .). conserve a sustained release of the api even after crushing ; very greatly increase the viscosity of an aqueous solution that has been used to extract the api from the microparticles . metformin tablets are prepared according to u . s . pat . no . 5 , 656 , 295 , examples 3 - 4 , column 10 , lines 20 to 63 , replacing the oxycodon with metformin . a tablet of counter example 1 is placed in a glass mortar and crushed . the crushed tablet is tested in a type ii dissolutest in accordance with the pharmacopoeia , at 37 ° c . and with stirring at 75 rpm , in the following media : 1 ) solution of hcl at ph 1 . 4 . it is noted that the release of the metformin is virtually immediate when the tablet has been crushed beforehand . the dissolution profiles are different according to the similarity factor f2 test : f2 & lt ; 50 ( see fig5 ). a solution of 755 g of metformin , 55 . 5 g of pvp and 3889 g of water is film - coated onto 216 g of cellulose neutral carriers . 455 g of metformin granules are film - coated with a mixture of 147 g of ethocel 20p , 7 . 35 g of pvp , 7 . 35 g of cremophor rh 40 , 34 . 3 g of castor oil and 2 . 254 kg of isopropanol . the microcapsules are then dried and screened through 500 μm . a mixture of 14 . 2 g of ethocel 20p , 1 . 5 g of triethyl citrate ( tec ), 7 . 1 g of magnesium stearate , 3 . 51 g of peg 6000 and 284 g of ethanol is film - coated onto 55 g of the microcapsules obtained above . the microcapsules are then dried and screened through 500 μm . 400 mg of microcapsules of example 5 are placed in a glass mortar and crushed . the microcapsules are recovered and tested in a type , ii dissolutest in accordance with the pharmacopoeia , at 37 ° c . and with stirring at 75 rpm , in a solution of hcl at ph 1 . 4 . fig6 represents the release profiles for the crushed microcapsules and for the intact microcapsules . it is noted that , in this case , the metformin release profile remains sustained and virtually identical to the profile of noncrushed microcapsules of example 5 . the dissolution profiles are similar according to the similarity factor f2 test : f2 & gt ; 50 . the ease with which various viscosity - modifying agents , used alone or as a mixture , can be drawn up is reported in table 1 . the ease with which they can be drawn up was evaluated on insulin syringes having a volume of 1 ml , through a needle ( 29g , ˜ 0 . 33 mm × 15 mm ). the drawing up was carried out with a sterile cotton filter placed at the end of the needle . the medium is considered to be nonpumpable if the time required to draw up 1 ml is greater than 5 min . the viscosity - modifying agents taken separately are not soluble and viscous in all the solvents . the mixture of the viscosity - modifying agents makes it possible to achieve viscosities which are sufficient for the system not to be pumpable in the three media considered . example according to the invention of particles of viscosity - modifying agents to be incorporated into a sachet or suspension formulation for the purpose of preventing misuse by injection of a suspension 6 g of pvp , 30 g of rhodigel , 30 g of ethocel 100p and 30 g of natrosol 250 hhx are granulated with a solution of ethanol . 1 g of triethyl citrate is added , with stirring , to a solution of 8 g of ethocel 07p , 2 . 1 g of stearyl alcohol and 110 g of ethanol at 70 ° c . after homogenization , the solution is then sprayed onto 50 g of granules obtained previously . the rheological behavior after dispersion in water of the film - coated granules in the intact form and after crushing is reported in table 2 : to correctly treat patients by providing them with a suspension that is easy to swallow , to combat misuse by means of a drastic increase in viscosity after crushing and suspension . a mixture of 65 g of paracetamol , 10 g of talc , 5 . 5 g of pvp and 350 g of water is film - coated onto 22 g of cellulose neutral carriers . a mixture of 14 . 2 g of ethocel 20p , 5 . 1 g of peg 6000 , 1 . 5 g of triethyl citrate and 284 g of ethanol is film - coated onto 55 g of the microcapsules previously obtained . the microcapsules are then dried and screened through 500 μm . a gel capsule is filled with the following mixture : 300 mg of the microcapsules of paracetamol previously obtained , 15 mg of microcapsules of example 5 and 3 mg of magnesium stearate . in the mixture thus formed , the microcapsules of paracetamol and of metformin cannot be discerned by size , by shape or by color . these microcapsules of paracetamol are immediate - release , ir , capsules . in the event of crushing in the case of an attempt at misuse , these microcapsules of paracetamol offer no resistance to the crushing , whereas the microcapsules of metformin according to the invention are protected by virtue of their overcoating ( cf . example 5 above ).
the invention relates to solid microparticulate oral dosage forms having a composition that prevents the misuse of the active pharmaceutical ingredient contained therein . the aim of the invention is to prevent the improper use of solid oral drugs for any use other than the therapeutic use officially approved by the appropriate public health authorities . another aim of the invention is to provide novel analgesic drugs which can be used to : prevent the misuse of , and addiction to certain analgesics and / or to control plasma concentration variability and / or to facilitate oral ; administration ; and / or to combine analgesics with one another and / or with one or more active ingredients in the same oral form . more specifically , the invention relates to a solid oral drug form comprising anti - misuse means and at least one active ingredient , which is characterized in that : at least part of the active ingredient is contained in microparticles ; and the anti - misuse means comprise anti - crushing means which enable the microparticles of the active ingredient to resist crushing , such as to prevent the misuse thereof . according to the invention , the drug form can also comprise means for preventing the misuse of the active ingredient following a possible liquid extraction process .