the present invention advantageously relates to dry microparticulate pharmaceutical forms , the composition of which makes it possible to prevent , or at the very least make very difficult , the crushing of the microparticles containing the ai . in a first embodiment of the invention , the anticrushing means comprise at least one caking agent ( m ). according to a variant , the drug form according to the invention is free of any combination consisting of at least one caking agent a ) and of at least one viscosifying agent b ). in this variant , the caking agent a ) is chosen from the class of hydrophobic compounds which act as a dry binder , preferably : from the group comprising cottonseed oils , soybean oils , palm oils , castor oils and mixtures of all or some of these oils ; and / or from the group of waxes , and even more preferably from the subgroup of waxes comprising hydrogenated cottonseed oils , hydrogenated soybean oils , hydrogenated palm oils , glyceryl behenates , hydrogenated castor oils , tristearins , tripalmitins , trimyristins , yellow waxes , hard fats , anhydrous dairy fats , lanolins , glyceryl palmitostearates , glyceryl stearates , lauric acid macrogolglycerides , cetyl alcohols , polyglyceryl diisostearates , diethylene glycol monostearates , ethylene monostearates , omegas 3 and mixtures of all or some of these waxes ; and / or from the group of fatty bases for suppositories comprising glycerol , triglycerides , theobroma oils , cocoa butters and mixtures of all or some of these products , and the viscosifying agent b ) is chosen from the following groups of polymers : polyacrylic acids and derivatives thereof , and / or polyalkylene glycols ( e . g . polyethylene glycol ), and / or polyvinylpyrrolidones , and / or gelatins , and / or polysaccharides , preferably from the subgroup comprising : sodium alginate , pectins , guars , xanthans , carrageenans , gellans and cellulose derivatives ( e . g . hydroxypropylmethylcellulose , methylcellulose , hydroxyethylcellulose , carboxy - methylcellulose ), preferably , the caking agent ( m ) is chosen such that , under shear , it is capable of converting the solid drug form into a nonpulverulent paste , making it difficult to crush the microparticles of ai . now , it is well known that the extraction of a compound to be concentrated from the viscous paste is extremely difficult . the caking agent ( m ) is chosen from the class of hydrophobic compounds which act as a dry binder , preferably : from the group comprising plant oils : cottonseed oils , soybean oils , palm oils , castor oils and mixtures of all or some of these oils ; and / or mineral oils and / or from the group of waxes , and even more preferably from the subgroup of waxes comprising hydrogenated cottonseed oil waxes , hydrogenated soybean oils , hydrogenated palm oils , glyceryl behenates , hydrogenated castor oils , tristearins , tripalmitins , trimyristins , yellow waxes , hard fats , anhydrous dairy fats , lanolins , glyceryl palmitostearates , glyceryl stearates , lauric acid macrogolglycerides , cetyl alcohols , polyglyceryl diisostearates , diethylene glycol monostearates , ethylene monostearates , omegas 3 and mixtures of all or some of these waxes ; and / or from the group of fatty bases for suppositories comprising glycerol , triglycerides , theobroma oils , cocoa butters and mixtures of all or some of these oils . in a second embodiment of the invention , the microparticulate drug form is characterized in that its anticrushing means comprise insoluble inert microbeads which have an average diameter of greater than or equal to 1 . 25 times , preferably 1 . 5 times , and even more preferably twice , the average diameter of the microparticles of ai . these microbeads which are insoluble in an aqueous or aqueous - alcoholic medium , cannot be compressed . due to the fact that the neutral beads are larger than the microparticles containing the ai , the crushing stresses are mainly borne by the neutral beads , thus protecting the microparticles containing the ai . they therefore make attempts at mechanical crushing ineffective . preferably , the insoluble neutral microbeads are chosen from the group of following substances : celluloses and insoluble derivatives thereof , polymethacrylic resins and derivatives thereof , silicas , talc , semolina , bentonite and mixtures thereof . in a third embodiment of the invention , the microparticulate drug form is characterized in that its anticrushing means comprise at least one lubricant ( l ). the role of the lubricant ( s ) is to greatly limit , or even eliminate , the abrasion of the microparticles containing the ai when they are mechanically crushed . the lubricant or slip agent 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 is 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 . in the presence of lubricant or slip agent , the powder composed of microparticles of active ingredient is not cohesive and has a very good flow . the lubricant is either simply mixed with the solid microparticulate pharmaceutical form , or else is directly deposited at the surface of the microparticles containing the ai by any means known to those skilled in the art , for example by spray - coating . by way of nonlimiting examples of lubricants or slip agents , mention may be made of : calcium stearate ; glyceryl palmitostearate ; hydrogenated plant oils ; magnesium oxide ; poloxamers ; polyethylene glycols ; polyvinyl alcohol ; sodium benzoate ; anionic , cationic or nonionic surfactants ; stearic acid ; corn starch ; talc ; colloidal silica ; zinc stearate , magnesium stearate , and mixtures thereof . the fraction by mass of lubricant in the solid pharmaceutical form according to the invention is , for example , between 1 % and 40 %. the microparticles according to the invention and which contain the ai have an average diameter of less than or equal to 1000 microns , preferably between 50 and 800 microns , and more preferably between 100 and 600 microns . the microparticles according to the invention and which contain the ai may be microcapsules for modified release of ai , i . e . microparticles coated with a polymer film deposited according to techniques known to those skilled in the art . on this subject , the article “ formes pharmaceutiques nouvelles ” [“ new pharmaceutical forms ”] by buri , puisieux , doelker and benoit , lavoisier 1985 , p 175 - 227 , will for example be consulted . advantageously , the drug form according to the invention cannot be converted into a dry form that can be administered by nasal aspiration . it should also be noted that this drug form according to the invention cannot be converted into an injectable form . according to a variant , the drug form according to the invention comprises immediate - release ai and / or modified - release ai . preferably , at least some of the microparticles of ai of the drug form according to the invention are microparticles , preferably microcapsules , for modified release of ai . advantageously , the microparticles of ai or the microcapsules of ai have an average diameter of less than or equal to 1000 μm , preferably between 50 and 800 microns , and even more preferably between 100 and 600 microns . according to another notable characteristic of the drug form according to the invention , extraction of the ai by chewing and / or crushing is ineffective . the ai used belongs , for example , to at least one of the following families of active substances : amphetamines , analgesics , appetite suppressants , antidepressants , antiepileptics , antimigraine agents , antiparkinsonian agents , antitussives , anxiolytics , barbiturates , benzodiazepines , hypnotics , laxatives , neuroleptics , opiates , psychostimulants , psychotropic agents , sedatives and stimulants . even more specifically , the ai used is chosen from the following compounds : methylphenidate , fentanyl , alfentanyl , pentazocine , pethidine , phenoperidine , remifentanil , sufentanil , acetorphine , acetylalphamethylfentanyl , acetylmethadol , alfentanil , allylprodine , alphacetylmethadol , alphameprodine , alphamethadol , alphamethylfentanyl , alpha - methylthiofentanyl , alphaprodine , anileridine , atropine , benzethidine , benzylmorphine , beta - hydroxyfentanyl , beta - hydroxymethyl - 3 - fentanyl , betacetylmethadol , betameprodine , betamethadol , betaprodine , bezitramide , buprenorphine , dioxaphetyl butyrate , cannabis , ketobemidone , clonitazene , codeine , coca , cocaine , codoxime , concentrate of poppy straw , desomorphine , dextromoramide , diampromide , diethylthiambutene , difenoxine , dihydroetorphine , dihydromorphine , dimenoxadol , dimepheptanol , dimethylthiambutene , diphenoxylate , dipipanone , drotebanol , ecgonine , ephedrine , ethylmethylthiambutene , etonitazene , etorphine , etoxeridine , fentanyl , furethidine , heroin , hydrocodone , hydromorphinol , hydromorphone , hydroxypethidine , isomethadone , levomethorphane , levomoramide , levophenacylmorphane , levorphanol , meperidine , metazocine , methadone , methyldesorphine , methyldihydromorphine , methyl - 3 - thiofentanyl , methyl - 3 - fentanyl , metopon , moramide , morpheridine , morphine , mppp , myrophine , nicomorphine , noracymethadol , norlevorphanol , normethadone , normorphine , norpipanone , opium , oxycodone , oxymorphone , para - fluorofentanyl , pepap , pethidine , phenampromide , phenazocine , phenomorphane , phenoperidine , piminodine , piritramide , proheptazine , propanolol , properidine , racemethorphane , racemoramide , racemorphane , remifentanil , sufentanil , thebacone , thebaine , thiofentanyl , tilidine , trimeperidine , acetyldihydrocodeine , codeine , dextropropoxyphene , dihydrocodeine , ethylmorphine , nicocodine , nicodicodine , norcodeine , pholcodine , propiram , the above embodiments can be taken in isolation or in combination with one another . 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 apparatus . 50 g of previously obtained granules 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 apparatus . the mean diameter of the microparticles obtained is 180 μm . these microparticles are virtually spherical . 35 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 . when these objects are subjected to shear , the layer containing the peg 6000 and the magnesium stearate protects the particles of active ingredient by reducing the effects of the shear .
the invention relates to the field of solid , oral , microparticulate 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 medicaments for any use other than the therapeutic use officially approved by the appropriate public health authorities . more specifically , the invention relates to a solid , oral drug form which is characterised in that at least one part of the active pharmaceutical ingredient is contained in the microparticles thereof and in that the inventive form comprises anti - crushing means which are intended to impede or completely prevent the crushing of the microparticles of the active pharmaceutical ingredient , such as to preclude the misuse thereof .