the membrane : the driving force for the mechanism of action of this dispenser is provided by osmotic imbibition of water through a semipermeable membrane causing a swelling or distortion of the enclosure until at some time a portion of the enclosure wall reaches its maximum elongation and breaks . the contents of the dispenser are then released to the environment . a principal factor controlling the rate of imbibition of water into the dispenser is the thickness and water permeability of the membrane and by choice of the membrane material the time to release of the active agent can be easily varied by as much as 1000 - fold . water permeability data which can be used to guide the selection of an appropriate membrane material can be found in articles by m . salame , journal of polymer science , polymer symposia series no . 41 , p . 1 - 15 ( 1973 ), and by j . barrie in &# 34 ; diffusion in polymers ,&# 34 ; j . crank and g . s . park ( eds ), academic press , london ( 1968 ), and by tables in &# 34 ; the guide to plastics ,&# 34 ; modern plastics encyclopedia , mcgraw hill , new york ( 19700265 ). amongst the preferred polymers with high water permeabilities are cellulose acetate , cellulose acetate butyrate , cellulose nitrate , crosslinked polyvinyl , alcohol , polyurethanes , nylon 6 , nylon 6 . 6 , and aromatic nylon such as nomex manufactured by dupont . preferred polymers with intermediate permeabilities include polyvinyl acetate , plasticized polyvinyl acetate , polyvinyl butyrate , and ethylene vinyl acetate co - polymers . preferred polymers with low water permeabilities include polyethylene , polypropylene , polyisobutylene , polyvinyl chloride , plasticized polyvinyl chloride , natural rubber , silicone rubber and polybutadiene . in general large changes in the time to release of the active agent from the dispenser are most economically and easily achieved by varying the membrane material while small changes of up to a factor of five are best achieved by varying the thickness of the membrane . in general a membrane thickness of at least one thousanth of an inch ( mil .) is required to obtain sufficient mechanical strength for handling of the dispenser . however , with small dispensers such as microcapsules lesser thicknesses are satisfactory . the membrane should be stable both to the outside environment and in the presence of a saturated solution of the contents of the dispenser . the membrane should also be relatively impermeable to the contents of the dispenser so that active agent or osmotic attractant is not lost by diffusion from the dispenser prior to rupture and so that a large osmotic pressure is obtained . this condition is met if the water flux into the dispenser is of the order of 5 or more and preferably 10 or more times greater than the loss of the active agent or osmotic agent from the dispenser . the extention to break : when placed in an osmotic environment , water is imbibed by the dispenser . at first the water fills any void space within the dispenser after which it will distend the dispenser until at some point the dispenser breaks and releases the active agent . this sequence is shown in fig . ( 1 ) where ( 1 ) represents the active agent together with any osmotic attractant present and ( 2 ) represents the semipermeable membrane . fig . ( 1 - a ) shows the initial state of the dispenser . when placed in an aqueous environment it slowly swells to the shape shown in fig . ( 1 - b ) and then as the ultimate elongation of the wall material is reached the wall breaks and releases the active agent as shown in fig . ( 1 - c ). one method of controlling the time at which release of the active agent takes place is to vary the ultimate elongation of the material from which the enclosure walls are made . one method of obtaining the ultimate elongation of a material is to clamp a small piece between the jaws of an instron testing machine and pull the jaws slowly apart at a rate of less than 0 . 1 cm / min until the point of ultimate elongation is reached . the ratio of the initial length to the final length can then be used to estimate how much water will be imbibed by the device before it breaks . in some cases ( for example , for reasons of biological compatability ) it may be desirable to make the semipermeable membrane from a material which has an unsuitably high elongation to break . in this case weak spots can be placed in the structure of the dispenser which will rupture before the rest of the membrane material approaches its ultimate elongation . thus in fig2 the dispenser is made by sealing two flat sheets of the semi - permeable membrane material 2 around a core 1 of the active agent ( and osmotic attractant if present ). the seal of this dispenser 6 can be made to rupture well before the membrane reaches its ultimate elongation . moreover , by altering the pressure and temperature used by a heat sealer or the glue used in a solvent seal the time of rupture can be controlled over wide limits . fig3 illustrates another form of weak spot 3 that can be incorporated into the dispenser , i . e ., by making the membrane wall 2 thinner at some point . when placed in an aqueous environment the capsule will break preferentially at this point . a third method of altering the time of rupture is illustrated in fig4 which shows a semipermeable membrane 2 in the form of a cylinder filled with an active agent ( and osmotic attractant if present ) 1 . the device is sealed at one end with a second material 4 . in this example the material 4 is made from a weaker material than the membrane material . for example the cylinder could be made from cellulose acetate and the cap from ethylene vinyl acetate . cellulose acetate is fairly tough and strong , while ethylene vinyl acetate is relatively weak and rubbery ; thus , when placed in an aqueous environment water is imbibed through the cellulose acetate semipermeable membrane . this water distorts both the cellulose acetate tube and the ethylene vinyl acetate end cap but because the ethylene vinyl acetate is much more rubbery and weaker it distorts more and finally ruptures well before the yield point of the cellulose acetate is reached . a fourth type of device is illustrated in fig5 which shows a container 5 made from an essentially impermeable material but which has a portion of the container walls made from a semipermeable membrane material 2 . as before the active agent ( and osmotic attractant if present ) cause water to be imbibed through the semipermeable membrane until at some time the container ruptures releasing the agent to the environment . by altering the ratio of the area of the impermeable wall to the membrane , the time to rupture can be altered . the osmotic pressure : if a semipermeable membrane separates a solution from pure water or two solutions of different concentrations the tendency to equalize concentrations will result in a flow of water from the less concentrated solution to the other one . if an attempt is made to impede this flow by exerting a pressure on the solution ( assuming for simplicity the other phase is pure solvent ) the rate of flow will be decreased . as the pressure is increased a point will be found when the flow is brought to a complete stop . this equilibrium pressure is called the osmotic pressure . osmotic pressures can be calculated in a variety of ways as for example those given by c . e . reid in &# 34 ; desalination by reverse osmosis ,&# 34 ; m . merten ( ed ), mit press , cambridge , mass . ( 1966 ). the simplest approximate method due to van &# 39 ; t hoff has the form where π is the osmotic pressure of the solution , c is the molar concentration of the solute in the solution , r is the gas constant and t is the absolute temperature . a few trial calculations show that osmotic pressures of saturated solutions of even moderately soluble compounds are very high and of the order of several hundreds and even thousands of pounds per square inch . typical values for saturated solutions are for example nacl ( 26 . 5w % solubility ) π = 5 , 300 psi , ( nh 4 ) 2 so 4 ( 43 . 2w % solubility ) π = 4 , 100 psi . the pressure required to distort and rupture the walls of the enclosures described in this invention is relatively small in comparison and thus the pressures that build up inside the enclosure prior to rupture usually do not inhibit the influx of water into the device . if , however , the enclosure walls must be thick for reasons of physical integrity , for example , or if the active agent has only a low solubility and hence osmotic pressure , or if the solution outside of the enclosure has a high osmotic pressure , the pressure that builds up inside the container may approach and even fall below the pressure required to burst the enclosure . in this case the performance of the device may be erratic and it may even not release the active agent at all . it then becomes desirable to supplement the osmotic pressure due to the active agent by incorporating a second compound called an osmotic attractant with the active agent into the enclosure . the osmotic attractant is drawn from those compounds which have relatively high osmotic pressures , do not degrade or interfere with the membrane or the enclosure walls , and do not interfere with the action of the active agent or the environment into which it is ultimately released . typical but non - limiting examples are sodium chloride , magnesium chloride , magnesium sulphate , potassium sulphate , sodium sulphite , sodium sulphate , sodium acetate , ammomium phosphate , ammonium sulphate , sucrose , glucose , raffinose , calcium lactate , and magnesium succinate . a measure of control of the time to release of the active agent is possible by choice of the amount and the osmotic pressure of the osmotic attractant added . the total osmotic pressure of the contents of the dispenser must exceed the pressure required to distort the dispenser both initially and just prior to rupture when the water imbibed will have diluted the system . the most reliable and reproducible operation is obtained if the amount of swelling of the dispenser and the solubility of the active agent ( and osmotic attractant if present ) are matched so that some excess agent remains just prior to rupture . in this way , the osmotic pressure of the internal environment ( which draws water into the dispenser ) is constant throughout the dispenser lifetime . in some cases this is not possible ; for example , with very soluble active agents , the dispenser will still swell and rupture but the ability to reproduce the same time to rupture for similar devices may be somewhat impaired . fabrication of the invention : the osmotic dispenser can be fabricated in any convenient shape for either physical insertion or implantation in the body , or for administration via the gastrointestinal tract , or for incorporation into a sprayable formulation , or for incorporation into a formulation which can be broadcast onto fields and waterways or for introduction into any desired environment . dimensions of the device can thus vary widely and are not of controlling importance . the lower limit of the size of the device is governed by the amount of the particular active agent to be supplied to the environment to elicit the desired response as well as by the form the dosage unit takes , for example in cases of specific body uses , implantate , bolus , iud , ivd , vaginal ring , uterine capsule for fertililty suppression , pessary , suppository and the like . this holds , too , with respect to the upper limit on the size of the device . in the above paragraph the device is used in its broad sense and may include a plurality of osmotic dispensers combined in some way to form a single larger device . thus when the dosage form includes a plurality of dispensers having individual variations with respect to the rate of agent release i . e ., a plural dosage form there is provided on administration a controlled release dosage form . in this condition , each dispenser becomes separately ruptured in due course depending on the film coating , thickness , composition , contents , etc . of each individual dispenser . in controlled fashion some dispensers rupture first to provide prompt release of agent , others later to provide a sustained effect . several of the methods of making the osmotic dispensers described above are given here by way of example . variations and other manufacturing techniques will be obvious to those skilled in the art . for large dispensers , injection molding can be used . in general the sequence used will consist of making the major portions of the enclosure in one molding cycle . the active agent and osmotic attractant if present is then placed in the enclosure and the enclosure sealed in a second injection molding cycle . the principal difficulties with injection molding are that it is difficult to economically and reproducibly make the membrane portion or any other portion of the enclosure less than 3 to 4 mils . thick , the internal volume of the enclosure should normally be at least 0 . 5 cm 3 in volume , the initial cost of the injection mold is high ( although this can be depreciated over a very large number of capsules ) and injection molding is not possible with all polymers . on the other hand , with injection molding it is easy to make enclosures with built - in weak spots , to make large devices and to make devices in large numbers very reproducibly . for small dispensers with internal volumes of 0 . 1 cm 3 to 5 cm 3 conventional tableting and coating as used in the pharmaceutical industry and described in &# 34 ; the theory and practice of industrial pharmacy &# 34 ; by l . lachman , h . a . lieberman , and j . l . kanig ( eds ), lea and febiger ( pub ), philadelphia ( 1970 ) or remington &# 39 ; s pharmaceutical sciences , a . osol et al . ( eds .) mack publishing co ., easton , pa . ( 1970 ) are preferred . in general with this equipment the membrane must form the entire wall of the enclosure but the process is very cheap and economical . an alternate method , with moderate sized devices with volumes of active agent 0 . 1 cm 3 and up , is to use pipes or tubes packed with active agent sealed at both ends . alternatively , the device can be made by laminating the active agent between two sheets of film . these last two methods are particularly suited to the economical fabrication of small numbers of dispensers for limited laboratory , field , or clinical trials . if the amount of the active agent to be delivered is small it can be diluted with an inert ingredient ( chalk , saw dust , etc .) or osmotic attractant and used with one of the devices described above or it can be made in the form of microcapsules . many forms of production of microcapsules are possible and are described in reviews by j . a . herbig in &# 34 ; the encyclopedia of polymer science and technology ,&# 34 ; interscience publishers 8 , 719 , ( 1968 ) and h . nack , &# 34 ; journal of the society of cosmetic chemists &# 34 ; 21 , 85 , ( 1970 ) and the references therein . active agent release from the invention : the invention described herein has many unique features hitherto unattainable by other means . one of these features is the ability to release a known amount of the agent after a known residence time of the dispenser in the environment . this feature allows almost any pattern of delivery of active agent to be obtained by making plural dosage forms consisting of several dispensers placed in the same environment at the same time ; each dispenser or subgroup of dispensers being made slightly different so that it releases its agent at a different time . by this mechanism the pattern of release of the active agent can be varied over a wide range . fig6 shows by way of example some of the patterns attainable . fig6 - a might be the release pattern desirable with an aquatic herbicide , for example , where delivery of the agent is required as a large dose every 3 to 6 months ; fig6 - b might be the pattern of release desired for drugs such as lithium chloride , potassium chloride or saliciyic acid and its derivitives which are known to produce undesirable side effects if given orally in a single readily available form . in this case the delivery would be spread over a period of 8 to 12 hours . fig6 - b might also represent the release of a pesticide , for example , parathion ( which because of its low solubility would be admixed with an osmotic attractant ). parathion is a potent pesticide but in soil it is metabolized rapidly by microorganisms and thus does not last through the growing season when given as a conventional dose . administration at a slow constant rate over a 3 to 4 month period as shown in fig6 - b is thus desirable . fig6 - c might represent the pattern of release desirable with antibiotic drugs such as tetracycline where a large initial &# 34 ; loading &# 34 ; dose is desired followed by a lower , more or less constant , holding dose . this type of dosage form is useful in cattle feed additives in the prevention of shipping fever where delivery of the drug over a 3 to 5 day period is required . while the invention has been described and illustrated with reference to certain preferred embodiments , those skilled in the art will appreciate that various modifications , changes , substitutions , and omissions can be made without departing from the spirit of the invention . it is intended therefore that the invention be limited only by the scope of the following claims .