JP2505922C - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION   The present invention is particularly useful in combination with osmotic pressure controlled drug delivery devices.
It relates to a cellulosic coating. Specifically, cellulosic coatings
Microporous used in connection with osmotically controlled drug release devices
It is combined with a pore former, preferably urea, to form a coating.   U.S. Pat. No. 4,330,338 (the '338 patent) discloses that
Describes a pharmaceutical coating in the form of an aqueous dispersion of a water-insoluble polymer
doing. In the '338 patent, the aqueous dispersion of the water-insoluble polymer is less than water.
Dissolve the polymer in a more volatile organic solvent and dissolve the solution thus formed in water.
Emulsify into the continuous phase and then add an organic solvent to form a latex coating.
Prepared by removal. Ethyl cellulose described in the '338 patent
Dispersion and other coatings may require the use of organic solvents with environmental, safety and toxicity concerns.
Provides an alternative to the base tablet coating.   Tablet cores coated according to the '338 patent release the active ingredient by diffusion
However, it is very slow unless a system with a large surface area is used.
It can be an ongoing process. Thus, the diffusion type as described in the '338 patent
Coating of nonpareil and beads with large surface area
Most often used to coat Prepared according to the disclosure of the '338 patent
Active tablets from tablets, for example, coated with a coating of ethylcellulose.
To facilitate the release of
Base (HPMC) is added. HPMC, a water-soluble polymer, is ethyl
Used to increase the water solubility of the cellulose coating, coating and then tablet core
In the environment, for example in the intestine. But such a rapid collapse
Is suitable for applications where the drug must be released over time.
is not.   U.S. Pat. No. 4,060,598 (the '598 patent) discloses a synthetic resin coating.
Disperses active ingredients through coatings (when exposed to aqueous use environments) To ensure that it is sufficiently porous so that it can be
Nyl ester, polyacrylate, polyvinyl acetal, polyvinyl chloride
From aqueous dispersions of synthetic polymers such as polyester or butadiene styrene copolymers
Combination of tablet coatings made with water-soluble or alkali-soluble substances
It describes its use by However, the method used in this patent is:
Not suitable for use with cellulose latex.   Accordingly, suitable organic materials for use in osmotically controlled drug delivery devices are provided.
There is a need for a tablet coating that does not include. Ideally, this coating
Changes to a microporous state upon exposure to an aqueous use environment, and the
It ensures the continuous release of the active ingredient into the environment.   The present invention relates to a cellulosic aqueous solution containing a water-soluble additive for forming pores and a plasticizer.
Disclose latexes, which are microporous in the environment in which they are used.
To form a coating that provides osmotically controlled release of useful ingredients from the core
So that it can be applied to the tablet core.   One category of coatings of the present invention is:   Cellulosic latex, surfactant, plasticizer, urea, nicotinamide
And a pore-forming agent selected from the group consisting of amino acids.
When exposed to water, the pore former dissolves and becomes insoluble in water.
It is characterized by being eluted leaving a base coating.   In addition, another category of osmotic pressure controlled release devices of the present invention are:   (A) Consisting of a cellulosic latex, a surfactant, a plasticizer and a pore-forming agent
A coating, wherein the cellulosic latex is emulsified with a cellulosic polymer.
Wherein the pore-forming agent is a cellulosic latex 100
0.1 to 75 grams per gram of pore former, when exposed to water
The pore former dissolves and forms a water-insoluble, microporous, cellulosic coating.
A coating that is eluted leaving; and   (B) an osmotic pressure of about 8 to 500 atm in the solution of the components of the core;
Core composed of 0.05 nanograms to 5 grams of useful ingredients Wherein the pore forming agent is urea, dimethyl sulfone,
A group consisting of cotinamide, saccharide, amino acid, diol and polyol
It is chosen from.   The exuded coating, according to scanning electron microscopy, was discontinuously woven with voids.
Porous composed of multiple continuous and independent chambers forming an enclosed network
Structure. These controlled porous coatings provide a water inlet and core composition solution
Function as both outlets.   Controlled porous coatings should be described as having a substantially sponge-like appearance.
Can be. The pores are continuous pores having openings on both sides of the microporous thin film.
Bend, or bend or partially bend in different directions.
Windings of regular or irregular shape, such as open continuous pores
May be interconnected pores through open passages, or
May be interconnected pores or other that can be identified by microscopy
In some cases. In general, a microporous thin film is
Number, the degree of bending of the microporous passage, and the porosity associated with the pore size and number.
Defined by The size of the pores in the microporous thin film can be determined using an electron microscope.
Can be easily confirmed by measuring the diameter of the pores observed on the surface of the material
it can. Generally, it has from 5% to 95% pores and from 10 Angstroms
Materials having pores as large as 100 microns can be used.   The coating of the present invention is impermeable to solutes dissolved inside the core during operation.
The inner or outer surface must not be covered by a layer of a material that is conductive.   Any cellulosic material that is permeable to water but impermeable to solutes
Polymer should also be used for aqueous dispersion in the form of latex or pseudolatex
Can be. The term “latex” has traditionally been used to describe the milky components of some plants and trees.
It is defined as a viscous emulsion secreted by the tract. Recently, late
Cans are aqueous colloidal dispersions of natural, synthetic or semi-synthetic polymers, such as   1. Natural latex obtained as a natural product from certain plants and trees,   2. Synthetic latex obtained by emulsion polymerization (ie, colloids in water
Emulsion to form microscopic spherical polymer particles suspended in Latex prepared from monomers that are polymerized as   3. Prepared by emulsifying bulk polymer mass directly in aqueous medium
Artificial latex, which is a colloidal dispersion of a polymer (such latexes are usually
Stabilized by surfactants. ) And so on.   Industrially, latex is often produced by emulsion polymerization. Monomer
Alternatively, the mixture of monomers is emulsified in water and the polymerization is initiated by the initiator in the aqueous phase.
Be started. Surfactants play a very important role in emulsion polymerization. At the interface
Their adsorption reduces the interfacial tension between the dispersed and continuous phases, causing their particles to be tightly bound.
Surrounded by hulls of water, it stabilizes the emulsion against condensation. Amphiphilic surfactant
The adsorbed layers of the agent direct their hydrophilic polar heads into the continuous phase,
On the other hand, the lipophilic non-polar tail is oriented in such a way that it is firmly retained in the dispersed phase.
Have been.   Other types of polymers and resins such as cellulosics used in the present invention
Those that are not produced as latex by emulsion polymerization are synthesized in advance.
It is prepared by latex formation by post-emulsification of the polymer. Surfactants are
It also plays an important role in stabilizing the latex produced by the method described above.   If the viscosity of the pure polymer is low enough, either a solution of the polymer or
There is a method of preparing an emulsion by emulsifying the mer. By emulsification technology
The preparation of artificial latex can be categorized into basically three different methods.
You. Ie   1. Solution emulsification: To prepare a polymer solution that is immiscible with water,
Dissolve in one solvent or mixed solvent and then add this solution to a suitable emulsifier and
Emulsify in water in the presence of the activator and remove the solvent.   2. Phase inversion: first mix the polymer with long chain fatty acids and invert the emulsion
Prepared by the method. When the fatty acids are sufficiently dispersed, the diluted aqueous alkaline solution is
Mix slowly into the mixture at a temperature of about 100 ° Fahrenheit. Initial product is polymer
Although water is being dispersed, when an aqueous solution is further added, phase inversion occurs and pouring into water occurs.
A dispersion of the limer particles and a self-emulsification are obtained. Polymer Molecules are self-dispersed in water or acid without the use of added emulsifiers.
It is chemically modified to obtain an emulsification.   Once the cellulosic polymer becomes a stable aqueous dispersion, the prepared dispersion (
Latex) to change the properties of the coating created by applying it to the tablet.
Adjustment additives such as plasticizers, pore formers and fillers can be added
You.   Suitable cellulosic polymers used in the present invention include cellulose ester
, Cellulose mixed esters, and cellulose ethers.   Each of the repeating units of glucose in the basic cellulose polymer backbone is derived
It has three possible hydroxyl groups. Cellulose useful in the present invention
The polymer has one, two or three hydroxyls per repeating glucose unit
Derivatized to the extent that it is converted to an ester or ether bond
. This derivatization of available hydroxyls often results in a degree of substitution D.S. S. age
And D. S. One is derivatized with one hydroxyl per glucose
D. S. 2 has two hydroxyls derivatized; S.
3 means that three hydroxyls are derivatized. Non-uniform guidance
In the embodiment, fractional D.C. such as 1.9, 2.2, 2.9, etc. S. It can be.   Representative esters useful in the present invention include cellulose acetate and cellulose.
Spropionate, cellulose butyrate, or cellulose acetate / p
Commonly used mixing agents such as lopionate and cellulose acetate / butylate
Sterol cellulose derivatives are mentioned. Typical ethers useful in the present invention are ethyl.
It is rucellulose. Other cellulose esters, cellulose ethers or
Combinations of derivatized cellulose polymers are also useful in the present invention, and
Although shown in the examples, this does not limit the scope.   The microporous cellulose coating of the present invention is useful for exposure to aqueous use environments.
Formed in situ by leaching or dissolving the pore former in the coating.
Can be Pores also form during coating due to gas generation during curing
It can be done.   Useful pore formers for use in the coatings of the present invention include urea, nicotine Amides and amino acids, and the osmotic pressure of the present invention regulates the release.
Useful pore formers for use in the device include urea, dimethyl sulfone, nicotine
Examples include amides, saccharides, amino acids, diols and polyols.   In addition, the pores are used to evaporate the components in the polymer latex or to
In a polymer latex that evolves gas during or before application of the resin
Formed in the wall by chemical reaction. Particularly suitable pore formers useful in the present invention
It is compatible with latex dispersion, non-toxic, highly water-soluble,
Because urine easily leaches out of the polymer to form a microporous coating,
Is prime.   Plasticizers reduce the secondary phase transition temperature and the modulus of cellulosic polymers.
Can be used for The workability and flexibility of the coating are improved, and the liquid permeability of the coating is increased.
Or drop. Plasticizers that can be used for the purposes of the present invention include cyclic plasticizers.
Agents and acyclic plasticizers. Representative plasticizers are phthalate, phosph
Citrate, citrate, adipate, tartrate, sebacate, succinate,
Glucolate, glycerolate, benzoate, myristate, polyethylene glycol
Selected from the group consisting of recall, polypropylene glycol and phenyl halide
Devour. Usually 0.001 to 50 parts of plasticizer per 100 parts of wall forming material
Or a mixture of plasticizers.   Including polyhydric alcohols such as polyalkylene glycols and their derivatives
Flux modifiers can be added to the wall to increase or decrease the permeability of the liquid. Especially
Suitable flux control agents include ethylene glycol dipropionate, ethylene glycol.
Recall butyrate, ethylene glycol diacetate, triethylene glycol
Ludiacetate, butylene glycol dipropionate, ethylene glycol
Succinic polyester, diethylene glycol and maleic polyester
And polyesters of triethylene glycol and adipic acid. Normal
The amount of flux modifier added to the material is sufficient to provide the desired permeability.
It depends on the film forming material and the flux modifier used to alter the permeability.
Fluctuate. Normally, 0.001 to 50 parts per 100 parts of film forming material.
Or higher amounts of flux control agent can be used to achieve the desired result.
Wear.   Surfactants adjust the surface energy of the dispersed cellulosic
To the film-forming material, thereby incorporating the polymer and other additives into the composite.
, Can improve mixing and dispersion. Sulfated, sulfonated or carboxylated
Silylated esters, amide alcohols, ethers, aromatic hydrocarbons, aliphatics
Anionic, cationic, and organic compounds including hydrocarbons, acylated amino acids and peptides, etc.
On-, non-ionic or amphoteric surfactants can be used. Examples of surfactants
Are sodium alkyl sulfates such as potassium laurate and sodium dodecyl sulfate.
, Hexadecyl sulfonic acid, sodium dioctyl sulfosuccinate, hexa
Decyl (cetyl) trimethylammonium bromide, dodecylpyridinium
Chloride, dodecylamine hydrochloride, N-dodecyl-N, N-dimethylbetaine,
Bile acids and salts thereof, gum arabic, tragacanth, polyoxyethylated nonylph
Enol (Igepal), sorbitol ester (spans), polysorbate (
Tweens), polyoxyethylated toctylphenol (Triton-X analog)
, Polyoxyethylene lauryl ether, polyoxyethylene cetyl ether,
Polyoxyethylene stearyl ether, polyoxyethylene oleyl ether
(Bridge analog), polyoxyethylene stearate (mildyl analog), Poloki
Polyoxyethylene-polyoxypropylene derivatives of the summer and poloxamine type
(Pluronic and tetronic), and phenothiazines, tricyclic compounds
Surface active agents such as harmful agents. Suitable surfactants are compatible with the film forming material.
In mixing, the ratio of hydrophilic groups to lipophilic groups by weight percent in surfactant
Can be selected using HLB, hydrophilic / lipophilic balance value of surfactant showing
You. Those with higher HLB are more hydrophilic surfactants and those with lower HLB are more hydrophilic.
It is a lipophilic surfactant. The HLB value required to mix with the film forming material is
Choose a surfactant with a known HLB number, mix it with the material and observe the results
Is determined by Homogeneous hybrids are formed with accurate HLB values, while non-uniform
A single mixture indicates that different values are needed. This new number is used as an indicator
It can be selected by using a conventional HLB value. The HLB value is
Many surfactants are known in the art and they
Can be decided. Usually, an HLB value of 10 or less indicates lipophilic behavior and 1
0 or more Shows hydrophilic behavior. The value of HLB is added algebraically. Therefore, low
Having a number in between two numbers by using a number and a higher number
A mixture of such surfactants is prepared. The concept of HLB isRemington's Pharmace
utical Sciences, 16th Ed., (Remington's Pharmaceutical Sciences, 16th Edition), Mack Pub.
Co. (Mac Publishing), (1980), pages 316-319.
You. The amount of surfactant required will depend on the coating mixture desired to be mixed with the film forming material.
Is the amount that will form a particular field that is mixed to form the coating.
Varies with surfactant and material. Usually, the amount of surfactant is 100 parts of the coating
In contrast, the range is from about 0.001 part to 40 parts.   The cellulose-based coating of the present invention includes, for example, "Encyclopedia of Polymer"
Science and Technology ”(Encyclopedia of Polymer Science and Technology) John W
iley & Sons, Inc., New York: (John Wiley and Sun, New York)
Fillers, Chapter 6, page 740
It may contain a suitable filler. Without limitation, suitable fillers
And silicates, oxides, carbonates, sulfates, carbon and polymerized fibers.   The cellulosic coatings of the present invention can be used for drug solutions, dispersions, pastes,
Cores made of particles, particles, fines, emulsions, suspensions or powders
Can be mixed with binders, dispersants, emulsifiers, wetting agents and dyes.
Can also be. As used herein, the term “drug” refers to physiological or pharmacological
Any effect that is locally effective and has a local or systemic effect on humans or animals
It also includes useful agents.   The process of producing the desired coating formulation includes plasticizers, pore formers and other desirable additives.
Additives and fillers to cellulosic latex, magnetic or high shear
Including mixing using a mixer. Coating is performed using a pan coater or fluidized bed equipment.
Can be given. Generally, a temperature of 50 ° C or higher is used, and the coating speed
Can be varied from 0.1 ml / min to 100 ml / min or more. Drugs
A suitable tablet core containing it is coated to the desired thickness and cured before use.   A preferred embodiment of the present invention has the following coating and core tablet specifications:
Indicated by an osmotically controlled drug delivery device; A. Coating specifications   Water-insoluble microporous wall surrounding a core tablet composition prepared by:   (I) cellulose which is permeable to water but substantially impermeable to solutes
Aqueous dispersion of a system polymer;   (Ii) formation of at least one water leaching pore dispersed through the coating;
The agent is 0.1 to 100% by weight relative to the total weight of (i) and (ii);   (Iii) Plasticizer and / or 100 parts of (i) and (ii) combined
Or 0 to 50 parts of a flux control additive;   (Iv) Fill 100 parts of the combined (i) and (ii) with water-insoluble
0 to 50 parts of filler material; and   (V) 100 parts of (i) and (ii) combined with no surfactant
From 40 parts. B. Core tablet specifications   Preferred specifications for the core tablet are as follows:   (I) Amount (size) of core drug: 0.05 nanogram to 5 grams or
Further drugs (including dosage forms for humans and animals);   (Ii) Osmotic pressure generated by the solution of the core;
And typically from 8 to 500 atmospheres; however, an osmotic pressure of zero or greater is acceptable;   (Iii) Solubility of the core: 90% or more of the core material initially placed
The continuous and uniform release of the above (zero order rate) is theoretically the soluble core
The ratio of the solubility S of the material to the density p of the soluble core material, ie S / p, is 0.1
Or less (typically this is one of the soluble core
0% saturates an amount of external liquid equal to the total volume of the original soluble core material)
Is foreseen. S / p ratios of 0.1 or more are in the practice of the present invention and the initial core
Results in a low release rate of the substance at zero order velocity. S / p is stability, release
Delivery speed and production possible The combination of characteristics can be selected to be acceptable.   There is no critical upper limit on the amount of drug that can be mixed into the core material,
Typically, the preferred core drug amounts described above are used. The lower limit of the drug to excipient ratio is
Desired drug solubility, desired osmotic activity for the core composition, desired time
Time and release profile and the pharmacological activity of the drug.
Typically, the wick contains 0.01% by weight of a useful agent, in a mixture with other solutes.
Contains 90% or more. Can be released from the device,
Representative compositions that can function without limitation include, without limitation, those
Is soluble in the liquid in the core as described. Wicked
The components are suitable for coating applications such as excipients, binders, lubricants, lubricants and bulking agents.
Can be mixed with those required to form a core tablet such as
You.Example   The following examples use the prepared cellulosic latex coatings of the present invention.
The preparation of the drug delivery device and one or more treatments into the environment in which it will be used
It shows a controlled release of the active ingredient.Example 1   A plurality of osmotic drug delivery systems comprising a 500 mg potassium chloride core were prepared.
Was. The prepared latex coating formulation contained 18 g of triethylcitrate.
250 ml of magnetically stirred Aquacoat^TM(Product name,
(Aquacoat) is described in the aforementioned '338 patent.
Stabilized by sodium lauryl sulfate and cetyl alcohol
Aqueous ethyl cellulose dispersion), and then 56 g of solid
Of urea. This conditioned latex before use
For one and a half hours and continuously during the application of the coating. Apply
Coater (Freund HCT Mini Hicoater)
) Was carried out at a spray rate of 1 ml / min and an inlet air temperature of 80 ° C. 200-40
0 A μm thick coating was applied. Tablets are cured at 50 ° C until tested
Was. Lysis was performed using standard U.S.A. S. P. Always stir at 50 rpm using a dissolution method # 2 instrument.
The test was performed in 900 ml of stirred 37 ° C. deionized water. Of potassium chloride
Release was monitored by a conductivity meter (Jenway Jenway PCM3).
The release profile shown in FIG. 1 shows that 90% or more of potassium chloride has zero order.
At a rate of. Figure 2 shows the core produced by this process.
4 shows photographs of a scanning electron microscope before and after leaching of the coating. No doubt about pore formation
It is clear.Example 2   The device of Example 1 was used. Lysis is performed using standard U.S.A. S. P. Dissolution method # 2 equipment
Of urea in various concentrations, stirred at 25 ° C. and 160 rpm using urea
In solution. Urea solutions were 1.64, 3.42 and 7.06 molar concentrations
Degree (molal). The amount of potassium chloride remaining in
It measured using the conductivity meter (Jenway Jenway PCM3). Zero order
The relationship between release rate and osmotic pressure difference across the coating is summarized in FIG.
. The linear dependence of the release rate on the osmotic pressure difference is mainly due to the release of potassium chloride.
Bleeding through microporous walls formed from conditioned cellulosic latex
This indicates that the operation was performed by the permeable pump mechanism.Example 3   The core used in this example was prepared from a granulating composition comprising:         Weight% Component          60 Diltiazem HCl          14 Adipic acid          12 citric acid            8 Sodium chloride            5 Polyvinylpyrrolidone (29-32K)            1 stearic acid            0.1 Magnesium stearate   The granulation composition has a Stokes (7/16 "deep concave tableting form).
(Stokes) tableting machine. The average tablet weight was 420 mg. Co
The ting was as described in Example 1. Dissolution is by standard USP dissolution method # 2
PH 1.25 at 37 ° C. constantly stirred at 50 rpm
Performed in 900 ml of buffer at pH 7.4. Diltiazem release is 290
Monitored by HPLC with UV at 238 nm or UV detection at 238 nm
did. A representative release profile is shown in FIG. 4, with 75% release at 20 hours
And shows that over 80% of the released drug is due to zero order kinetics.Example 4   Except for using dibutyl sebacate as the plasticizer, the core and coating procedures were performed.
The one outlined in Example 1 was used. Has a coating thickness of 310 μm
The release of potassium chloride from this type of device was rather slow (6 hours
%).Example 5   Except that the pore forming agent was sorbitol and the plasticizer was dibutyl sebacate,
The wicking and coating procedure outlined in Example 1 was used. Thickness 200
The release of potassium chloride from these devices with a μm coating is rapid.
(100% in 2 hours).Example 6   Except that the pore former was nicotinamide and the plasticizer was dibutyl sebacate
The wicking and coating procedure outlined in Example 1 was used. Thickness 30
The release of potassium chloride from these devices with a 0 μm coating is slow.
(Less than 10% in 8 hours). Example 7   Except that the pore former was glycine and the plasticizer was dibutyl sebacate
The wicking and coating procedure outlined in Example 1 was used. 235 μm thick
The release of potassium chloride from these devices with different coatings is slow.
(11% over 22 hours).Example 8   Kevlar for increased coating strength^TM(Product name, Kevlar) Pulp polymerization filling
Using the core and coating procedure outlined in Example 1 except that the agents were added.
Was.Example 9   Outlined in Example 1 except that urea was dissolved in water before adding to latex
A core and coating procedure was used.Example 10   Example 1 except that the coating was prepared at 60 ° C. using a fluid bed coater.
The core and coating procedure described above was used. Potassium chloride from these devices
Release was slower than equipment covered with the same thickness of bread (1 hour
4%). The coating for these devices is the same as for pan-coated devices of the same thickness.
It was stronger than the coating.Example 11   Cellulose acetate in methanol / methylene chloride (50:50 by volume)
The pseudolatex is prepared by dissolving the sheet (10% by weight). The resulting solution is
Lauric sulfate in aqueous solution under conditions of continuous high-speed shearing and stirring.
Mix with ril sodium. The resulting emulsion is stirred with ultrasound and then averaged.
Qualify. The organic solvent is removed under reduced pressure to form a pseudo latex dispersion. This latte
The box is Aquacoat^TMExample 1 as a substitute for (product name, aqua coat)
~ Used as described in No. 10.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a modified cellulosic latex coating (Aqu) of the present invention.
1 illustrates a representative release profile of a tablet of potassium chloride coated with acoat ^™ (Aquacoat ^™ ), 24% (g / g polymer) triethyl citrate, 75% (g / g polymer) urea. FIGS. 2A and 2B show the conditioned cellulosic latex (Aquac).
oat ^™ [trade name, Aquacoat], 24% (g / g polymer) triethyl citrate, 75% (g / g polymer) urea, to elute the pore former in the coating of the tablet of the present invention. 2A and 2B are SEM (scanning electron microscope) photographs (magnification: 1000) showing states before (FIG. 2A) and after (FIG. 2B) immersion in water for the purpose of immersion. FIG. 3 illustrates the osmotic mechanism of release from a tablet coated according to the present invention. FIG. 4 shows a cellulosic latex prepared according to the present invention (Aquaco
FIG. 3 illustrates a representative release profile of a diltiazem-HCl tablet coated with at ^™ [trade name, Aquacoat], 24% (g / g polymer) triethyl citrate, 75% (g / g polymer) urea. .

Claims (1)

Claims: 1. A coating comprising a cellulosic latex, a surfactant, a plasticizer, and a pore-forming agent selected from the group consisting of urea, nicotinamide and amino acids, which has been exposed to water. The coating, wherein the pore former is dissolved and eluted leaving a microporous cellulosic coating insoluble in water. 2. The coating of claim 1, further comprising at least one of a flux modifier or a filler. 3. The coating according to claim 1, wherein the cellulosic latex is formed by emulsification of a cellulosic polymer. 4. The coating of claim 3, further comprising at least one of a flux modifier or a filler. 5. The pore-forming agent is 0.1 to 7 per 100 grams of cellulosic latex.
4. The coating of claim 3 which is a porogen in an amount of 5 grams. 6. The coating of claim 5, wherein said pore former is urea. 7. (a) a coating comprising a cellulose-based latex, a surfactant, a plasticizer and a pore-forming agent, wherein the cellulose-based latex is formed by emulsification of a cellulose-based polymer; Cellulosic latex 1
A pore former in an amount of 0.1 to 75 grams per 00 grams, which upon exposure to water dissolves and elutes leaving a microporous cellulosic coating insoluble in water. An osmotic pressure release comprising a core comprising from 0.05 nanograms to 5 grams of a useful component that produces an osmotic pressure of about 8 to 500 atmospheres in a solution of the core component. A device that is regulated and controlled. 8. The apparatus according to claim 7, wherein said pore forming agent is selected from the group consisting of urea, dimethyl sulfone, nicotinamide, saccharide, amino acid, diol and polyol.