Connect public, paid and private patent data with Google Patents Public Datasets

Laminated drug dispenser

Download PDF

Info

Publication number
US3926188A
US3926188A US52372074A US3926188A US 3926188 A US3926188 A US 3926188A US 52372074 A US52372074 A US 52372074A US 3926188 A US3926188 A US 3926188A
Authority
US
Grant status
Grant
Patent type
Prior art keywords
drug
lamina
dispenser
core
release
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
Inventor
Richard W Baker
Robert M Gale
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alza Corp
Original Assignee
Alza Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0087Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0092Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules, nanotubes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0002Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0004Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0048Eye, e.g. artificial tears
    • A61K9/0051Ocular inserts, ocular implants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time

Abstract

A three layer laminate drug dispenser comprising a core lamina of a crystalline drug of low water solubility dispersed homogeneously in a polymer matrix of permeability, P, to the drug, the lamina having a thickness, 2t, and a surface area, A, interposed between outer laminas made of a drug release rate controlling polymer of permeability, P'', to the drug, each outer lamina having a thickness, t'',and the combined, exposed surface area of the outer laminas being A'' wherein the expression

and the expression

k being a constant whose value is dependent upon the geometrical shape of the dispenser.

Description

United States Patent 1191 Baker et al.

[ Dec. 16, 1975 1 1 LAMINATED DRUG DISPENSER [75] Inventors: Richard W. Baker, Bend, Oreg.; Robert M. Gale, San Jose, Calif.

[52] US. Cl. 128/260; 424/19; 128/213 [51] Int. Cl. A61M 31/00; A61K 27/12 [58] Field of Search 128/156, 260, 268, 2 R,

[56] References Cited UNITED STATES PATENTS 2,928,770 3/1960 Bardani 424/21 3,184,386 5/1965 Stephenson 424/21 3,416,530 12/1968 Ness 128/260 3,618,604 11/1971 Ness 128/260 3,625,214 12/1971 Higuchi 128/260 3,797,485 3/1974 Urquhart 128/213 3,851,648 12/1974 Brooke 128/260 Primary ExaminerAldrich F. Medbery Attorney, Agent, or Firm-Thomas E. Ciotti; Paul L. Sabatine', Edward L. Mandell 5 7 ABSTRACT A three layer laminate drug dispenser comprising a core lamina of a crystalline drug of low water solubility dispersed homogeneously in a polymer matrix of permeability, P, to the drug, the lamina having a thickness, 2!, and a surface area, A, interposed between outer laminas made of a drug release rate controlling polymer of permeability, P, to the drug, each outer lamina having a thickness, z',and the combined, exposed surface area of the outer laminas being A wherein the expression and the expression A P r 2; (DA 3 I 13 Claims, 5 Drawing Figures U.S. Patent De c. 16, 1975 Sheet 1 of2 3,926,188

FIG.|

FIG.2

DISPENSERS 0F EXAMPLE I TIME HR.)

US. Patent Dec.16, 1975 Sheet2of2 3,926,188

5 7| 2 2 5 2 2 2 w 2 DI Wu 0 VA 3 CL I F 0 G 0 l S R F E O 5 8 2 N l C... DI 0 8 0 D I 5 7| 0 5 5 2 0 0 0 0 0 0 O 0 6 M m m 00 6 4 DISPENSERS 0F EXAMPLE 5 I60 I I I 2'0 2:305 MC; $5 5m TIME HR.)

LAMINATED DRUG DISPENSER BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to a laminated dispenser for dispensing active agents by a diffusion mechanism. More specifically it relates to dispensers comprising a three layer sandwich-type laminate which dispense crystalline drugs of low water solubility.

2. Description of the Prior Art Numerous sustained release dispensers, particularly ones for dispensing drugs, have been developed recently which comprise an active agent which is confined within a polymer and which dispense an agent by a diffusion mechanism in which the agent permeates through the polymer. The aim of these devices is to dispense the drug at a more or less constant rate for a prolonged period of time which results in improved therapy compared to drugs delivered by periodic ingestion of pills, injections or drops. Basically such dispensers are of two types: monolithic and reservoir. In a monolithic device the drug or other active agent is dispersed in a polymer which is permeable to the drug. The time rate of release of agent from such devices has been studied and reported. It is proportional to time A plot of release rate versus time for a monolithic device gives a curve which starts at a high rate and continuously declines. Notwithstanding this varying release rate, monolithic devices have the commercial attractiveness of being inexpensive to make.

T. Higuchi, J. Plzurm. Sci., 50, 874 (I961); T. J. Roseman et al.. J. Plmrm. Sci., 61, 46 (1972); and H. K. Lonsdale. R. W. Baker. Controlled Release of Biologically Active Agents, Ed. C. Tanquery. Plenum Press, New York (1974) In a reservoir device the active agent is confined within a container formed of a polymer which is permeable to the agent. The agent may be neat or combined with a solid or liquid carrier. In copending, commonly assigned applications Ser. Nos. 42,786 and 185,208, filed June 2, 1970 and Sept. 30, 1971, respectively, embodiments of reservoir devices in which the agent release is substantially constant are disclosed. The two basic features of those embodiments which permit such release are: formulating the agent in a liquid or solid carrier whose permeability to the drug is greater than the permeability of the polymer defining the container to the agent; and maintaining the concentration of the agent in the carrier at saturation for the effective dispensing lifetime of the device. For some agents such reservoir embodiments are the only type of diffusion device for dispensing the agent at a practical controlled rate. Such embodiments also provide the advantages of providing a substantially constant release of agent-- which is an important factor as regards efficacy and safety in many therapeutic regimens. The disadvantages of reservoir devices as compared to monolithic devices is economic--the former being more complex and hence more costly to make than the latter.

SUMMARY OF THE INVENTION provided there is a particular correlation between the respective permeabilities, thicknesses and exposed surface areas of the core lamina and the outer lamina(s).

0 having a permeability, P. to the drug, a thickness, 1,

and an exposed surface area, A, .from which drug is released wherein is greater than about 2 and is at least three times k being a constant whose value is dependent upon the geometrical shape of the laminate.

Preferably is greater than 3 and is at least 10 times L. 1 i P I The laminated drug dispenser of this invention may be in the form of a three layered sandwich or in the form of a concentric laminate. This type of device combines the good drug release kinetics of the reservoir devices with the ease and cheapness of manufacture of monolithic devices.

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings like reference numerals refer to like parts, and:

FIG. 1 is a cross-sectional view of a drug dispenser of this invention;

FIG. 2 is a graphical representation of the release rates of the devices described in Example 1, infra;

FIG. 3 is a graphical representation of the release rates of the devices dese'fibed in Example 2, infra;

FIG. 4 is a graphical Representation of the release rates of tl ie devices descflled in Example 3, infra; and

FIG. 5 l an elevational perspective view of another drug dlfir of this invlition.

DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 illustrates a drug dispenser, generally designated 10, of this invention. Dispenser is a three layer sandwich-type laminate in the shape of a thin, circular disc comprising a core lamina 11 sandwiched between two outer laminas 12,13. Core lamina 11 consists of solid particles of drug 14 dispersed within a matrix material 15. Material 15 has a permeability, P, and core lamina 11 has a thickness, 21. The edge 16 of core lamina 11 defines the surface area, A, thereof which is exposed to the environment.

Outer laminas 12,13 each have a thickness, t, and a permeability, P, to the drug. Surfaces 17,18 of laminas 12,13 define a combined surface area, A, thereof which is exposed to the environment. (The area defined by the axial edges of laminas 12,13 is also exposed but is negligible relative to area A'.)

Dispenser 10 releases drug 14 at surfaces 16,17 and 18 by a diffusion mechanism. Drug molecules initially dissolve in matrix material 15 and permeate therethrough either to exposed surface 16 or to outer laminas 12,13 and therethrough to exposed surfaces 17,18.

The molecules which reach exposed surfaces 16,17,18 are removed or cleared therefrom through contact with body fluids and/or body tissue. When the respective permeabilities and thicknesses of core lamina 11 and outer laminas 12,13 are correlated as set forth above, that is is greater than about 2, drug will be released from surfaces 17,18 at a substantially constant rate as long as matrix material 15 is saturated with the drug. In contrast, drug is released from edge 16 at a constantly declining rate proportional to time"? However, by correlating the permeabilities, thicknesses and exposed surface areas of core lamina l 1 and outer laminas 12,13 as set forth above, the amount of drug released from edge 16 is substantially less than the amount of drug released from surfaces 17,18. Accordingly, the overall release rate from dispenser 10 is dominated by the release rate of drug from surfaces 17,18 and thus the overall release rate approximates the substantially constant release rate from those surfaces. In this respect, the greater the magnitude of and the greater the difference between the magnitude of the expression and the magnitude of the expression the closer is this approximation. If

is less than 2, the outer membranes do not control the drug release rate which declines proportional to time? If the area of exposed core is too high or the permeability of the core is too high and release of drug from the edge predominates and again the release rate declines proportional to time. In the intermediate region, how ever, which is the subject of this invention, neither of these effects predominates and drug release is almost constant with time. The release rates of these laminates are, of course, not as constant as the release rates of comparable prior art reservoir devices in which the core is not exposed to the environment. However, for many therapies the degree of release rate constancy afforded by these laminates is acceptable. Thus they provide a viable, less expensive alternative to the reservoir devices in such instances.

FIG. 5 illustrates another drug dispenser, generally designated 19, of the invention. Dispenser 19 is a concentric-type laminate in the shape of a cylinder comprising a cylindrical core lamina 20 and an outer concentric lamina 21 which covers the axial surface of core lamina 20. Core lamina 20, like core lamina 11, comprises particles of drug 14 dispensed within a matrix material 15. It is functionally equivalent to core lamina 1 1. The ends 22,23 of core lamina 20 define the surface area, A, thereof which is exposed to the environment. Core lamina 20 has a diameter, 2!. Outer concentric lamina 21 has a permeability, P, to the drug and has a thickness, t. Lamina 21 is functionally identical to laminas 12,13 and may be made from the same materials as the latter. The axial surface 24 of lamina 21 defines the surface area, A, thereof which is exposed to the environment. (The area defined by the radial edges of lamina 21 is also exposed but is negligible relative to area A'.)

Dispenser 19 releases drug 14 at surfaces 22,23,24 by a diffusion mechanism identical to that described above with respect to dispenser 10. The correlations between the thicknesses, permeabilities and exposed surface areas of laminas 20,21 of dispenser 19 required to permit dispenser 19 to release drug at a substantially constant rate are the same as those described above. with respect to dispenser 10.

Drug 14 is solid (crystalline) and should have a low water solubility. Low water solubility is a requirement so that the drug does not function to any significant extent as an osmotic attractant to imbibe water from the use environment into core lamina 11. If substantial water is imbibed, the drug 14 may be released by an osmotic bursting mechanism rather than a diffusion mechanism. This would affect the release rate of drug in an undesirable manner. The degree of water solubility will in many-instances depend on the permeability of matrix material 15 to water. If material 15 has a high permeability tovwater, the water solubility of the drug should be correspondingly low and vice versa. Drugs which are less than about 4% by weight soluble in water are preferred.

The particle size of drug- 14 is notcritical. Particle sizes in the-range of l to 20p. will normally be used since they are easy to handle and may be readily dispersed homogeneously in matrix material by conventional techniques.

The loading of drug 14 in core lamina 11 is important because it may affect the permeability of core lamina 11 to the drug. At high drug loadings (greater than about 25% by weight) lamina 11 has a tendency to become microporous over the. devices lifetime. This occurs because as drug particles 14 dissolve in matrix 15 and diffuse therefrom, voids are left in the matrix. At such high drug loadings, the void volume is sufficient to make the portion of lamina 11 which has been v depleted of drug microporous. Such microporosity will cause the permeability of core lamina 11 to increase. Indeed, high drug loadings provide a means for making the permeability of the core lamina 11 substantially greater than the permeability of the outer laminas even though the same polymer is used in both. The drug loading of lamina 11 will'depend upon the drug dosage regimen desired, with higher loadings providing greater dosages and/or more sustained release. Usually the loading will be in the range of 30 to 75% by weight of the core lamina.

The nature of the drug will depend upon the therapy for which the device is intended. Drugs which produce a localized effect at the administration site or a systemic effect at a site remote from the administration site may be used. Such drugs include inorganic and organic compounds, for example, drugs which act on the central nervous system such as hypnotics and sedatives, psychic energizers, tranquilizers, anticonvulsants, muscle relaxants and anti-parkinson agents, antipyretics and anti-inflammatory agents, local. anesthetics,

anti-spasmodicsand antiulcer agents, prostaglandins,

anti-microbials, hormonal agents, estrogenic steroids, progestational steroids, such as for contraceptive purposes, sympathomimetic drugs, cardiovascular drugs, diuretics, anti-parasitic agents, hypoglycemic drugs and ophthalmic drugs.

Matrix material 15 may be made from a polymeric material which'is homogeneous and substantially imperforate (i.e., it has no man-made perforations) or it may be made from a polymer which has been made microporous by conventional techniques. In either instance its permeability to the drug should be known. (Known techniques are available to determine the permeabilitiesof such materials. See for instance US. Pat. No. 3,710,795.) Examplesof substantially imperforate polymers which may be used are poly(butylmethacrylate), plasticized poly(vinylchloride), plasticized soft nylon, natural rubber, poly(isoprene), poly(isobutylene), poly(butadiene), poly(ethylene), poly(vinylidene chloride), cross-linked poly(vinylpyrrolidone), chlorinated poly(ethylene), poly(4,4-isopropylidene diphenylene carbonate), ethylene-vinylacetate copolymer, plasticized ethylene-vinylacetate copolymer, vinlyidene chloride-acrylonitrile copolymer, vinyl chloride-diethyl fumerate copolymer, silicone rubbers, especially the medical grade poly(dimethylsiloxanes), ethylene-propylene rubber, silicone-carbonate copolymers and vinylidene chloridevinyl chloride copolymer.

Microporous materials have pores which range in size from at least about 10 A to several hundred microns, but usually not more than about 100 microns. Examples of materials from which microporous structures may be made are regenerated, insoluble, nonerodible cellulose, acylated cellulose, esterified cellulose, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose acetate diethylaminoacetate, poly(urethanes), poly(carbonates), modified insoluble collagen, cross-linked poly(- vinyl alcohol), epoxy resins and poly(olefins) or poly(- vinylchlorides). These materials may be made microporous by well known procedures such as coprecipitation or leaching out incorporated salts, soap micelles, starch or like materials. See, for example, J. D. Ferry, Chemical Reviews, 18, 373 (1935), and In: Synthetic Polymer Membranes, by R. E. Kesting, McGraw-Hill, 1971.

Outer laminas 12,13 may be made from the same polymers as matrix material 15, provided, of course, that the permeability of the material 15 to the drug is greater than the permeability of the material forming laminas, 12,13. It will be appreciated that either of outer laminas 12,13 may be made from a drugimpermeable material. In such an instance, the effective thickness (the maximum thickness through which the drug must permeate to reach a permeable outer lamina) of core lamina 11 will be twice that of an embodiment in which both laminas 12,13 are drug permeable and the exposed outer lamina surface area from which drug is released will be half that of an embodiment in which both laminas 12,13 are drug permeable. It is also within the scope of this invention to make laminas 12,13 from different polymeric materials of different drug permeability and to make them of different thicknesses.

The shape and size of the dispenser of this invention will depend upon the environment in which it is intended to be used. If the dispenser is intended to be implanted or inserted, its size and shape will be compatible with the size and shape of the implantation or insertion site. For instance, if it is intended to be used as an ocular insert, it will be sized and shaped for insertion and retention in the eye. Likewise, if intended for insertion in other body cavities, such as the vagina, uterus, mouth and gastrointestinal tract, it will be sized and shaped accordingly. In most instances it will be acceptable to employ regular shapes. As indicated above, the value of k in the expression will depend on the geometrical shape of the dispenser. For three-layered sandwich elliptical shaped dispensers such as dispenser 10, k has a value of 4. Its value for other sandwich-type dispensers of regular geometrical shape may be calculated, (e.g., for a circle it is 8). For cylindrical concentric laminate dispensers such as are listed above as useful for dispenser 19, k has a value of /s. The value of k for other concentric laminates of other cross-sectional shapes (e.g., hexagonal, square, elliptical) may be calculated.

The sandwich-type laminates of this invention may be manufactured according to well-known techniques. Depending upon the particular polymers comprising the core lamina and outer laminas, the laminate may be bonded together with or without binders. Various binders are well known in the art. See for instance the Encyclopedz'a of Polymer Science and Technology, John Wiley & Sons, Vol. 8, 1968. If a binder is used, it, of course, should be compatible with the polymers constituting the laminas and should not affect or interfere with the drug permeation through the laminas or alter the drug deleteriously in any manner. Conventional laminating machines and techniques may be used, with the particular temperatures and pressures employed varying with the polymers involved. The laminates may be formed as continuous sheets and the dispensers of this invention cut or punched therefrom by known techniques. The concentric-type laminates of the invention may also be formed by well-known techniques such as coextrusion.

While the dispensers have hereinabove been described as dispensers for releasing drugs for human or animal therapy, it will also be appreciated that they may be used to release other active agents in other environments, provided such agents are solid and have low water solubility as described above. Such active agents include, for example, pesticides, herbicides, germicides, biocides, algicides, rodenticides, fungicides, insecticides, anti-oxidants, plant growth promoters and inhibitors, preservatives, surfactants, disinfectants, catalysts, fermentation agents, nutrients, plant minerals, sex sterilants, plant hormones, air purifiers, microorganism attenuators and the like.

EXAMPLES The following examples illustrate the dispensers of this invention and their performance relative to dispensers outside the scope of the invention as defined herein, and are not intended to limit the scope of the invention in any manner.

Example 1 A. A physostigmine (Eserine) dispenser, such as might be inserted in the eye to dispense Eserine thereto, was made as follows. Fifty parts Eserine (particle size approximately 5 microns), and 50 parts of ethylene/vinyl acetate copolymer (brand name, Elvax 40) were mixed homogeneously on a rubber mill. The resulting mixture was melt pressed into a 200 micron thick film. This film was then placed in a vacuum/heat laminator and a 150 micron thick sheet of ethylene/vinyl acetate copolymer (brand name, Elvax 40) was laminated to each side of it. Duplicate 5.8 mm X 13.5 mm ellipses were punched from the resulting three layer laminate. P, P, A and A, for these elliptical dispensers were determined and the values for the expressions were calculated therefrom and are reported in Table 1 below.

B. Duplicate Eserine dispensers were made in accordance with part A above except that the outer laminas were each 75 microns thick. The data for these dispensers are also reported in Table 1 below.

C. For comparison, duplicate Eserine dispensers were made in accordance with part A above except 8 that the outer laminas were each 13 microns thick. The data for these dispensers are also reported in Table 1 below.

The release rates of the dispensers of A, B and C were determined by placing individual devices in polymer mesh bags and suspending the bags from a vertically reciprocating bar into vessels containing 50 ml water stirred at 37C. The Eserine concentration in the water was measured at regular intervals by UV analysis, the water being changed after each measurement. Eserine release rates were calculated from the measurements. FIG. 2 is a plot of these release rates versus time. As indicated by the plots of FIG. 2, the release rate of the dispensers of B is substantially more constant than that of the dispensers of C and that of A is even more constant than B. This is a reflection of the increasing value of the expression P r P as reported in Table 1.

Example 2 Two sets of chloramphenicol dispensers were made by the general procedure of Example 1A. The core lamina was made from 66 parts chloramphenicol (particle size approximately 5 microns) and 34 parts copolymer and was 125 microns thick. The outer laminas were 50 microns thick and 17.5 microns thick, respectively. The data for these two sets, designated 2A and 2B, are reported in Table 2 below.

Table 2 P P A A P I r k (A' )2 (cm (cm t P A 2A 16 0.1 1.23 4.5 605 2B 90 16 0.1 1.23 l 6 605 The release rates of dispensers 2A and 2B were determined by the procedure described in Example 1. FIG. 3 is a plot of these release rates versus time.

Example 3 Table 3 P P A A P I k A 2 (cm) (cm I P A The release rates of dispensers 3A and 3B were determined by the procedure described in Example 1. FIG. 4 is a plot of these release rates versus time.

Modifications of the dispensers described herein which are obvious to persons of skill in the art are intended to be within the scope of the following claims.

We claim:

1. An active agent dispenser comprising a laminate of:

a. a core lamina of particles of a crystalline active agent of low water solubility dispersed in a solid material having a permeability, P, to the agent, the core lamina having a thickness 2t, and an exposed surface area, A, from which agent is released, and being partially covered by;

b. at least one outer lamina made of an active agent release rate controlling polymer having a permeability, P, to the agent, a thickness, 1, and an exposed surface area, A', from which agent is released wherein is greater than about 2 and is at least three times .L'... r P

10 is greater than 3 and is at least 10 times L. r P I 4. The drug dispenser of claim 2 wherein P is substantially greater than P.

5. The drug dispenser of claim 4 wherein P is substantially greater than P because of the porosity of the core lamina caused by the quantity of drug therein.

6. The drug dispenser of claim 2 wherein the drug initially comprises 30 to by weight of the core lamina.

7. The drug dispenser of claim 2 wherein the solubility of the drug in water is less than 4% by weight.

8; The drug dispenser of claim 2 wherein the drug is chloramphenicol, physostigmine or hydrocortisone, and the dispenser is sized and shaped for insertion in the cul-de-sac of a human eye.

9. The dispenser of claim 1 wherein the dispenser is a three layer sandwich-type laminate, said core lamina being sandwiched between a pair of said outer lamina.

10. The dispenser of claim 9 wherein the laminate has the geometrical shape of a thin circular disc and k is 8.

11. The dispenser of claim 9 wherein the laminate has the geometrical shape of a thin elliptical disc and k is 4.

12. The dispenser of claim 1 wherein the dispenser is a concentric-type laminate, said outer lamina being outerly concentric to said core lamina and covering the axial surface of said core lamina.

13. The dispenser of claim 12 wherein the laminate is cylindrical in shape and k has a value of Ma.

Claims (13)

1. An active agent dispenser comprising a laminate of: a. a core lamina of particles of a crystalline active agent of low water solubility dispersed in a solid material having a permeability, P, to the agent, the core lamina having a thickness 2t, and an exposed surface area, A, from which agent is released, and being partially covered by; b. at least one outer lamina made of an active agent release rate controlling polymer having a permeability, P'', to the agent, a thickness, t'', and an exposed surface area, A'', from which agent is released wherein
2. The dispenser of claim 1 wherein the agent is a drug.
3. The drug dispenser of claim 2 wherein
4. The drug dispenser of claim 2 wherein P is substantially greater than P''.
5. The drug dispenser of claim 4 wherein P is substantially greater than P'' because of the porosity of the core lamina caused by the quantity of drug therein.
6. The drug dispenser of claim 2 wherein the drug initially comprises 30 to 75% by weight of the core lamina.
7. The drug dispenser of claim 2 wherein the solubility of the drug in water is less than 4% by weight.
8. The drug dispenser of claim 2 wherein the drug is chloramphenicol, physostigmine or hydrocortisone, and the dispenser is sized and shaped for insertion in the cul-de-sac of a human eye.
9. The dispenser of claim 1 wherein the dispenser is a three layer sandwich-type laminate, said core lamina being sandwiched between a pair of said outer lamina.
10. The dispenser of claim 9 wherein the laminate has the geometrical shape of a thin circular disc and k is 8.
11. The dispenser of claim 9 wherein the laminate has the geometrical shape of a thin elliptical disc and k is 4.
12. The dispenser of claim 1 wherein the dispenser is a concentric-type laminate, said outer lamina being outerly concentric to said core lamina and covering the axial surface of said core lamina.
13. The dispenser of claim 12 wherein the laminate is cylindrical in shape and k has a value of 1/8 .
US3926188A 1974-11-14 1974-11-14 Laminated drug dispenser Expired - Lifetime US3926188A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US3926188A US3926188A (en) 1974-11-14 1974-11-14 Laminated drug dispenser

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US3926188A US3926188A (en) 1974-11-14 1974-11-14 Laminated drug dispenser
GB4228975A GB1477813A (en) 1974-11-14 1975-10-15 Sustained release dispensers
DE19752549856 DE2549856C2 (en) 1974-11-14 1975-11-06
JP13614875A JPS6059203B2 (en) 1974-11-14 1975-11-12
CA 239459 CA1056685A (en) 1974-11-14 1975-11-12 Active agent dispenser and process for making same
FR7534821A FR2290891B1 (en) 1974-11-14 1975-11-14

Publications (1)

Publication Number Publication Date
US3926188A true US3926188A (en) 1975-12-16

Family

ID=24086191

Family Applications (1)

Application Number Title Priority Date Filing Date
US3926188A Expired - Lifetime US3926188A (en) 1974-11-14 1974-11-14 Laminated drug dispenser

Country Status (6)

Country Link
US (1) US3926188A (en)
JP (1) JPS6059203B2 (en)
CA (1) CA1056685A (en)
DE (1) DE2549856C2 (en)
FR (1) FR2290891B1 (en)
GB (1) GB1477813A (en)

Cited By (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4182330A (en) * 1977-07-25 1980-01-08 Alza Corporation Means for administering amphipathic medicament
EP0025699A1 (en) * 1979-09-12 1981-03-25 Eli Lilly And Company Device for drug delivery to ruminants
US4304232A (en) * 1979-03-14 1981-12-08 Alza Corporation Unit system having multiplicity of means for dispensing useful agent
US4314557A (en) * 1980-05-19 1982-02-09 Alza Corporation Dissolution controlled active agent dispenser
DE3115763A1 (en) * 1981-04-18 1982-11-04 Edgar Dr Med Lenhard Medical depot probe for the local protracted release of active substance
US4370313A (en) * 1981-10-26 1983-01-25 Eaton Laboratories, Inc. Nitrofurantoin dosage form
US4483846A (en) * 1982-02-05 1984-11-20 Ono Pharmaceutical Co., Ltd. Long-lasting three-layered pharmaceutical film preparations
US4552751A (en) * 1980-10-17 1985-11-12 Ono Pharmaceutical Co., Ltd. Long-lasting multi-layered film preparation
US4564364A (en) * 1983-05-26 1986-01-14 Alza Corporation Active agent dispenser
US4571039A (en) * 1983-04-15 1986-02-18 Stanley Poler Eye-medicating contact-lens construction
DE3538038A1 (en) * 1984-10-26 1986-04-30 Alza Corp A device for administering a drug to the colon
US4601893A (en) * 1984-02-08 1986-07-22 Pfizer Inc. Laminate device for controlled and prolonged release of substances to an ambient environment and method of use
US4639244A (en) * 1983-05-03 1987-01-27 Nabil I. Rizk Implantable electrophoretic pump for ionic drugs and associated methods
US4693895A (en) * 1984-10-26 1987-09-15 Alza Corporation Colon delivery system
EP0293066A2 (en) * 1987-05-27 1988-11-30 Alza Corporation Dispenser comprising displaceable matrix with solid state properties
WO1989003232A1 (en) * 1987-10-09 1989-04-20 Bukh Meditec A/S A medical device for introduction into a body cavity
US4830860A (en) * 1986-10-30 1989-05-16 Pfizer Inc. Stressed polymeric device for controlled release of a substance to an ambient environment
US4841968A (en) * 1986-09-26 1989-06-27 Southern Research Institute Antithrombotic/thrombolytic suture and methods of making and using the same
US4863445A (en) * 1984-07-30 1989-09-05 Baxter Travenol Laboratories, Inc. Assembly for inhibiting microbial growth in collected fluid
US4880633A (en) * 1986-03-12 1989-11-14 Merck & Co., Inc. Transdermal drug delivery system
US4906475A (en) * 1988-02-16 1990-03-06 Paco Pharmaceutical Services Estradiol transdermal delivery system
US4908027A (en) * 1986-09-12 1990-03-13 Alza Corporation Subsaturated transdermal therapeutic system having improved release characteristics
US4938759A (en) * 1986-09-02 1990-07-03 Alza Corporation Transdermal delivery device having a rate controlling adhesive
US4959208A (en) * 1987-10-19 1990-09-25 Ppg Industries, Inc. Active agent delivery device
US4973468A (en) * 1989-03-22 1990-11-27 Cygnus Research Corporation Skin permeation enhancer compositions
US4994275A (en) * 1988-07-05 1991-02-19 Pfizer Inc. Veterinary devices
US5004610A (en) * 1988-06-14 1991-04-02 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US5035886A (en) * 1987-10-19 1991-07-30 Ppg Industries, Inc. Active agent delivery device
US5053227A (en) * 1989-03-22 1991-10-01 Cygnus Therapeutic Systems Skin permeation enhancer compositions, and methods and transdermal systems associated therewith
US5059426A (en) * 1989-03-22 1991-10-22 Cygnus Therapeutic Systems Skin permeation enhancer compositions, and methods and transdermal systems associated therewith
US5071645A (en) * 1987-10-19 1991-12-10 Ppg Industries, Inc. Process of producing an active agent delivery device
US5088505A (en) * 1987-08-08 1992-02-18 Akzo N.V. Contraceptive implant
WO1992002211A1 (en) * 1990-08-09 1992-02-20 Endocon, Inc. Multiple drug delivery system
US5124157A (en) * 1989-08-18 1992-06-23 Cygnus Therapeutic Systems Method and device for administering dexmedetomidine transdermally
US5217718A (en) * 1989-08-18 1993-06-08 Cygnus Therapeutic Systems Method and device for administering dexmedetomidine transdermally
US5342623A (en) * 1986-09-12 1994-08-30 Alza Corporation Subsaturated transdermal therapeutic system having improved release characteristics
US5466233A (en) * 1994-04-25 1995-11-14 Escalon Ophthalmics, Inc. Tack for intraocular drug delivery and method for inserting and removing same
EP0684815A1 (en) * 1993-02-19 1995-12-06 AHN, Sam, S. Drug delivery system using hollow fibers
US5508038A (en) * 1990-04-16 1996-04-16 Alza Corporation Polyisobutylene adhesives for transdermal devices
EP0710491A1 (en) * 1994-11-02 1996-05-08 The Population Council Center For Biomedical Research Subdermally implantable device
US20020148138A1 (en) * 2001-04-06 2002-10-17 Egan Brian A. Smart tread boot covers
US20030157140A1 (en) * 2000-05-26 2003-08-21 Kanji Takada Nonoral preparation having three-layer structure
US20040210208A1 (en) * 2003-04-16 2004-10-21 Cook Incorporated Medical device with therapeutic agents
WO2005110364A2 (en) * 2004-04-30 2005-11-24 Allergan, Inc. Drug delivery systems and methods for treatment of an eye
WO2006040141A2 (en) * 2004-10-12 2006-04-20 Capsulution Nanoscience Ag Segmented device for the delayed release of molecules in a tangential direction through thin films and uses thereof
US20070043332A1 (en) * 2003-07-10 2007-02-22 Galen (Chemiclas) Liimited Intravaginal drug delivery devices
USRE39588E1 (en) 1987-11-09 2007-04-24 Alza Corporation Transdermal drug delivery device
US7585517B2 (en) * 2003-09-18 2009-09-08 Macusight, Inc. Transscleral delivery
US20110066141A1 (en) * 2009-09-11 2011-03-17 Cook Incorporated Implantable medical device having an anti-gastric distress agent
US20110098797A1 (en) * 2009-10-23 2011-04-28 Cleek Robert L Drug eluting composite
US20110112618A1 (en) * 2009-11-09 2011-05-12 Cleek Robert L Drug eluting composite
US8222271B2 (en) 2006-03-23 2012-07-17 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
US8277830B2 (en) 2009-01-29 2012-10-02 Forsight Vision4, Inc. Posterior segment drug delivery
US8367097B2 (en) 2005-02-09 2013-02-05 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US8486052B2 (en) 2001-06-12 2013-07-16 The Johns Hopkins University School Of Medicine Reservoir device for intraocular drug delivery
US8492400B2 (en) 2006-02-09 2013-07-23 Santen Pharmaceutical Co., Ltd. Stable formulations, and methods of their preparation and use
US8623395B2 (en) 2010-01-29 2014-01-07 Forsight Vision4, Inc. Implantable therapeutic device
US8663639B2 (en) 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
US8715712B2 (en) 2011-09-14 2014-05-06 Forsight Vision5, Inc. Ocular insert apparatus and methods
US20140271783A1 (en) * 2011-10-14 2014-09-18 Purdue Research Foundation Prefabricated pharmaceutical dosage forms from functional polymer films
US8905963B2 (en) 2010-08-05 2014-12-09 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US20160067178A1 (en) * 2014-09-08 2016-03-10 ProMed Pharma, LLC Methods for manufacturing implants
US9421126B2 (en) 2009-06-03 2016-08-23 Forsight Vision5, Inc. Anterior segment drug delivery
US9474756B2 (en) 2014-08-08 2016-10-25 Forsight Vision4, Inc. Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
US9492315B2 (en) 2010-08-05 2016-11-15 Forsight Vision4, Inc. Implantable therapeutic device
US9504771B2 (en) 2009-11-09 2016-11-29 W. L. Gore & Associates, Inc. Drug eluting composite
US9526654B2 (en) 2013-03-28 2016-12-27 Forsight Vision4, Inc. Ophthalmic implant for delivering therapeutic substances
US9750636B2 (en) 2012-10-26 2017-09-05 Forsight Vision5, Inc. Ophthalmic system for sustained release of drug to eye
US9883968B2 (en) 2012-09-13 2018-02-06 Forsight Vision4, Inc. Fluid exchange apparatus and methods

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63143581A (en) * 1986-12-05 1988-06-15 Nissha Printing Co Ltd Hologram molded article
JPH0444601U (en) * 1990-08-22 1992-04-15
JPH0444666U (en) * 1990-08-22 1992-04-15
JP3720386B2 (en) * 1993-12-27 2005-11-24 住友製薬株式会社 Controlled drug release formulations

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2928770A (en) * 1958-11-28 1960-03-15 Frank M Bardani Sustained action pill
US3184386A (en) * 1958-05-02 1965-05-18 Burroughs Wellcome Co Prolonged action medicinal tablets
US3416530A (en) * 1966-03-02 1968-12-17 Richard A. Ness Eyeball medication dispensing tablet
US3618604A (en) * 1969-06-09 1971-11-09 Alza Corp Ocular insert
US3625214A (en) * 1970-05-18 1971-12-07 Alza Corp Drug-delivery device
US3797485A (en) * 1971-03-26 1974-03-19 Alza Corp Novel drug delivery device for administering drug into blood circulation in blood vessel
US3851648A (en) * 1973-10-11 1974-12-03 Mead Johnson & Co Zero-order release device

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3854480A (en) * 1969-04-01 1974-12-17 Alza Corp Drug-delivery system
US3630200A (en) * 1969-06-09 1971-12-28 Alza Corp Ocular insert
US3832252A (en) * 1970-09-29 1974-08-27 T Higuchi Method of making a drug-delivery device

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3184386A (en) * 1958-05-02 1965-05-18 Burroughs Wellcome Co Prolonged action medicinal tablets
US2928770A (en) * 1958-11-28 1960-03-15 Frank M Bardani Sustained action pill
US3416530A (en) * 1966-03-02 1968-12-17 Richard A. Ness Eyeball medication dispensing tablet
US3618604A (en) * 1969-06-09 1971-11-09 Alza Corp Ocular insert
US3625214A (en) * 1970-05-18 1971-12-07 Alza Corp Drug-delivery device
US3797485A (en) * 1971-03-26 1974-03-19 Alza Corp Novel drug delivery device for administering drug into blood circulation in blood vessel
US3851648A (en) * 1973-10-11 1974-12-03 Mead Johnson & Co Zero-order release device

Cited By (103)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4182330A (en) * 1977-07-25 1980-01-08 Alza Corporation Means for administering amphipathic medicament
US4304232A (en) * 1979-03-14 1981-12-08 Alza Corporation Unit system having multiplicity of means for dispensing useful agent
EP0025699A1 (en) * 1979-09-12 1981-03-25 Eli Lilly And Company Device for drug delivery to ruminants
US4314557A (en) * 1980-05-19 1982-02-09 Alza Corporation Dissolution controlled active agent dispenser
US4552751A (en) * 1980-10-17 1985-11-12 Ono Pharmaceutical Co., Ltd. Long-lasting multi-layered film preparation
DE3115763A1 (en) * 1981-04-18 1982-11-04 Edgar Dr Med Lenhard Medical depot probe for the local protracted release of active substance
US4370313A (en) * 1981-10-26 1983-01-25 Eaton Laboratories, Inc. Nitrofurantoin dosage form
US4483846A (en) * 1982-02-05 1984-11-20 Ono Pharmaceutical Co., Ltd. Long-lasting three-layered pharmaceutical film preparations
US4571039A (en) * 1983-04-15 1986-02-18 Stanley Poler Eye-medicating contact-lens construction
US4639244A (en) * 1983-05-03 1987-01-27 Nabil I. Rizk Implantable electrophoretic pump for ionic drugs and associated methods
US4564364A (en) * 1983-05-26 1986-01-14 Alza Corporation Active agent dispenser
US4601893A (en) * 1984-02-08 1986-07-22 Pfizer Inc. Laminate device for controlled and prolonged release of substances to an ambient environment and method of use
US4863445A (en) * 1984-07-30 1989-09-05 Baxter Travenol Laboratories, Inc. Assembly for inhibiting microbial growth in collected fluid
DE3538038A1 (en) * 1984-10-26 1986-04-30 Alza Corp A device for administering a drug to the colon
US4693895A (en) * 1984-10-26 1987-09-15 Alza Corporation Colon delivery system
US4880633A (en) * 1986-03-12 1989-11-14 Merck & Co., Inc. Transdermal drug delivery system
US4938759A (en) * 1986-09-02 1990-07-03 Alza Corporation Transdermal delivery device having a rate controlling adhesive
US4908027A (en) * 1986-09-12 1990-03-13 Alza Corporation Subsaturated transdermal therapeutic system having improved release characteristics
US5342623A (en) * 1986-09-12 1994-08-30 Alza Corporation Subsaturated transdermal therapeutic system having improved release characteristics
US4841968A (en) * 1986-09-26 1989-06-27 Southern Research Institute Antithrombotic/thrombolytic suture and methods of making and using the same
US4830860A (en) * 1986-10-30 1989-05-16 Pfizer Inc. Stressed polymeric device for controlled release of a substance to an ambient environment
EP0293066A3 (en) * 1987-05-27 1989-10-11 Alza Corporation Dispenser comprising displaceable matrix with solid state properties
EP0293066A2 (en) * 1987-05-27 1988-11-30 Alza Corporation Dispenser comprising displaceable matrix with solid state properties
US5088505A (en) * 1987-08-08 1992-02-18 Akzo N.V. Contraceptive implant
WO1989003232A1 (en) * 1987-10-09 1989-04-20 Bukh Meditec A/S A medical device for introduction into a body cavity
US5035886A (en) * 1987-10-19 1991-07-30 Ppg Industries, Inc. Active agent delivery device
US5071645A (en) * 1987-10-19 1991-12-10 Ppg Industries, Inc. Process of producing an active agent delivery device
US4959208A (en) * 1987-10-19 1990-09-25 Ppg Industries, Inc. Active agent delivery device
USRE39588E1 (en) 1987-11-09 2007-04-24 Alza Corporation Transdermal drug delivery device
US4906475A (en) * 1988-02-16 1990-03-06 Paco Pharmaceutical Services Estradiol transdermal delivery system
US5633008A (en) * 1988-06-14 1997-05-27 Osborne; James L. Method of administering nicotine transdermally
US6165497A (en) * 1988-06-14 2000-12-26 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US5004610A (en) * 1988-06-14 1991-04-02 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US4994275A (en) * 1988-07-05 1991-02-19 Pfizer Inc. Veterinary devices
US4973468A (en) * 1989-03-22 1990-11-27 Cygnus Research Corporation Skin permeation enhancer compositions
US5053227A (en) * 1989-03-22 1991-10-01 Cygnus Therapeutic Systems Skin permeation enhancer compositions, and methods and transdermal systems associated therewith
US5059426A (en) * 1989-03-22 1991-10-22 Cygnus Therapeutic Systems Skin permeation enhancer compositions, and methods and transdermal systems associated therewith
US5217718A (en) * 1989-08-18 1993-06-08 Cygnus Therapeutic Systems Method and device for administering dexmedetomidine transdermally
US5124157A (en) * 1989-08-18 1992-06-23 Cygnus Therapeutic Systems Method and device for administering dexmedetomidine transdermally
US5508038A (en) * 1990-04-16 1996-04-16 Alza Corporation Polyisobutylene adhesives for transdermal devices
WO1992002211A1 (en) * 1990-08-09 1992-02-20 Endocon, Inc. Multiple drug delivery system
EP0684815A4 (en) * 1993-02-19 1997-04-23 Sam S Ahn Drug delivery system using hollow fibers.
EP0684815A1 (en) * 1993-02-19 1995-12-06 AHN, Sam, S. Drug delivery system using hollow fibers
US5466233A (en) * 1994-04-25 1995-11-14 Escalon Ophthalmics, Inc. Tack for intraocular drug delivery and method for inserting and removing same
US5660848A (en) * 1994-11-02 1997-08-26 The Population Council, Center For Biomedical Research Subdermally implantable device
US5756115A (en) * 1994-11-02 1998-05-26 The Population Coucil, Center For Biomedical Research Contraceptive method using a subdermally implantable device
EP0710491A1 (en) * 1994-11-02 1996-05-08 The Population Council Center For Biomedical Research Subdermally implantable device
US7695729B2 (en) * 2000-05-26 2010-04-13 Kanji Takada Nonoral preparation having three-layer structure
US20030157140A1 (en) * 2000-05-26 2003-08-21 Kanji Takada Nonoral preparation having three-layer structure
US20020148138A1 (en) * 2001-04-06 2002-10-17 Egan Brian A. Smart tread boot covers
US9522082B2 (en) 2001-06-12 2016-12-20 The Johns Hopkins University Reservoir device for intraocular drug delivery
US8486052B2 (en) 2001-06-12 2013-07-16 The Johns Hopkins University School Of Medicine Reservoir device for intraocular drug delivery
US9180046B2 (en) 2001-06-12 2015-11-10 The Johns Hopkins University School Of Medicine Reservoir device for intraocular drug delivery
US7780647B2 (en) 2003-04-16 2010-08-24 Cook Incorporated Medical device with therapeutic agents
US20080051737A1 (en) * 2003-04-16 2008-02-28 Cook Incorporated Medical device with therapeutic agents
US20040210208A1 (en) * 2003-04-16 2004-10-21 Cook Incorporated Medical device with therapeutic agents
US7306580B2 (en) 2003-04-16 2007-12-11 Cook Incorporated Medical device with therapeutic agents
WO2004093962A1 (en) * 2003-04-16 2004-11-04 Cook Incorporated Medical device with therapeutic agents.
US20070043332A1 (en) * 2003-07-10 2007-02-22 Galen (Chemiclas) Liimited Intravaginal drug delivery devices
US7585517B2 (en) * 2003-09-18 2009-09-08 Macusight, Inc. Transscleral delivery
WO2005110364A3 (en) * 2004-04-30 2006-07-13 Allergan Inc Drug delivery systems and methods for treatment of an eye
WO2005110364A2 (en) * 2004-04-30 2005-11-24 Allergan, Inc. Drug delivery systems and methods for treatment of an eye
US20090117170A1 (en) * 2004-10-12 2009-05-07 Capsulution Nanoscience Ag Segmented device for the delayed release of molecules in a tangential direction through thin films and uses thereof
WO2006040141A3 (en) * 2004-10-12 2006-10-05 Capsulution Nanoscience Ag Segmented device for the delayed release of molecules in a tangential direction through thin films and uses thereof
WO2006040141A2 (en) * 2004-10-12 2006-04-20 Capsulution Nanoscience Ag Segmented device for the delayed release of molecules in a tangential direction through thin films and uses thereof
US8637070B2 (en) 2005-02-09 2014-01-28 Santen Pharmaceutical Co., Ltd. Rapamycin formulations and methods of their use
US9381153B2 (en) 2005-02-09 2016-07-05 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US9387165B2 (en) 2005-02-09 2016-07-12 Santen Pharmaceutical Co., Ltd. Rapamycin formulations and methods of their use
US8367097B2 (en) 2005-02-09 2013-02-05 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US8663639B2 (en) 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
US8927005B2 (en) 2005-02-09 2015-01-06 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US8492400B2 (en) 2006-02-09 2013-07-23 Santen Pharmaceutical Co., Ltd. Stable formulations, and methods of their preparation and use
US8658667B2 (en) 2006-02-09 2014-02-25 Santen Pharmaceutical Co., Ltd. Stable formulations, and methods of their preparation and use
US8486960B2 (en) 2006-03-23 2013-07-16 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
US9452156B2 (en) 2006-03-23 2016-09-27 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
US8222271B2 (en) 2006-03-23 2012-07-17 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
US9851351B2 (en) 2009-01-29 2017-12-26 Forsight Vision4, Inc. Posterior segment drug delivery
US9417238B2 (en) 2009-01-29 2016-08-16 Forsight Vision4, Inc. Posterior segment drug delivery
US8298578B2 (en) 2009-01-29 2012-10-30 Forsight Vision4, Inc. Posterior segment drug delivery
US8808727B2 (en) 2009-01-29 2014-08-19 Forsight Vision4, Inc. Posterior segment drug delivery
US8277830B2 (en) 2009-01-29 2012-10-02 Forsight Vision4, Inc. Posterior segment drug delivery
US9066779B2 (en) 2009-01-29 2015-06-30 Forsight Vision4, Inc. Implantable therapeutic device
US8399006B2 (en) 2009-01-29 2013-03-19 Forsight Vision4, Inc. Posterior segment drug delivery
US8795712B2 (en) 2009-01-29 2014-08-05 Forsight Vision4, Inc. Posterior segment drug delivery
US9421126B2 (en) 2009-06-03 2016-08-23 Forsight Vision5, Inc. Anterior segment drug delivery
US20110066141A1 (en) * 2009-09-11 2011-03-17 Cook Incorporated Implantable medical device having an anti-gastric distress agent
US20110098797A1 (en) * 2009-10-23 2011-04-28 Cleek Robert L Drug eluting composite
US20110112618A1 (en) * 2009-11-09 2011-05-12 Cleek Robert L Drug eluting composite
US9320890B2 (en) 2009-11-09 2016-04-26 W. L. Gore & Associates, Inc. Drug eluting composite
US9504771B2 (en) 2009-11-09 2016-11-29 W. L. Gore & Associates, Inc. Drug eluting composite
US8623395B2 (en) 2010-01-29 2014-01-07 Forsight Vision4, Inc. Implantable therapeutic device
US8939948B2 (en) 2010-06-01 2015-01-27 Forsight Vision5, Inc. Ocular insert apparatus and methods
US8905963B2 (en) 2010-08-05 2014-12-09 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US9492315B2 (en) 2010-08-05 2016-11-15 Forsight Vision4, Inc. Implantable therapeutic device
US9033911B2 (en) 2010-08-05 2015-05-19 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US9861521B2 (en) 2010-08-05 2018-01-09 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US8715712B2 (en) 2011-09-14 2014-05-06 Forsight Vision5, Inc. Ocular insert apparatus and methods
US20140271783A1 (en) * 2011-10-14 2014-09-18 Purdue Research Foundation Prefabricated pharmaceutical dosage forms from functional polymer films
US9883968B2 (en) 2012-09-13 2018-02-06 Forsight Vision4, Inc. Fluid exchange apparatus and methods
US9750636B2 (en) 2012-10-26 2017-09-05 Forsight Vision5, Inc. Ophthalmic system for sustained release of drug to eye
US9526654B2 (en) 2013-03-28 2016-12-27 Forsight Vision4, Inc. Ophthalmic implant for delivering therapeutic substances
US9474756B2 (en) 2014-08-08 2016-10-25 Forsight Vision4, Inc. Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
US20160067178A1 (en) * 2014-09-08 2016-03-10 ProMed Pharma, LLC Methods for manufacturing implants

Also Published As

Publication number Publication date Type
JP1332917C (en) grant
JPS5170807A (en) 1976-06-18 application
DE2549856C2 (en) 1985-01-03 grant
GB1477813A (en) 1977-06-29 application
DE2549856A1 (en) 1976-05-20 application
FR2290891A1 (en) 1976-06-11 application
CA1056685A1 (en) grant
FR2290891B1 (en) 1978-11-10 grant
CA1056685A (en) 1979-06-19 grant
JPS6059203B2 (en) 1985-12-24 grant

Similar Documents

Publication Publication Date Title
US3699963A (en) Therapeutic adhesive patch
US5128145A (en) Dosage form for Parkinson's disease, spasticity and muscle spasms
US6328992B1 (en) Cannabinoid patch and method for cannabis transdermal delivery
US4769028A (en) Pharmaceutical product, in medical bandage form
US6773721B1 (en) Osmotic caplet
US5614212A (en) Method of transdermally administering high molecular weight drugs with a polymer skin enhancer
US3944064A (en) Self-monitored device for releasing agent at functional rate
US4955945A (en) Dispenser for the vaporization of active substances to be inhaled
US4077407A (en) Osmotic devices having composite walls
US4588580A (en) Transdermal administration of fentanyl and device therefor
US4685918A (en) Lipid osmotic pump
US3901232A (en) Integrated device for administering beneficial drug at programmed rate
US4036228A (en) Osmotic dispenser with gas generating means
US4898582A (en) Portable infusion device assembly
US4058122A (en) Osmotic system with laminated wall formed of different materials
US7182227B2 (en) Aerosol delivery system
US4615699A (en) Transdermal delivery system for delivering nitroglycerin at high transdermal fluxes
US4230105A (en) Transdermal delivery of drugs
US4624847A (en) Drug delivery device for programmed delivery of beneficial drug
Thacharodi et al. Development and in vitro evaluation of chitosan-based transdermal drug delivery systems for the controlled delivery of propranolol hydrochloride
US4008719A (en) Osmotic system having laminar arrangement for programming delivery of active agent
US4210139A (en) Osmotic device with compartment for governing concentration of agent dispensed from device
US3854480A (en) Drug-delivery system
US5120548A (en) Swelling modulated polymeric drug delivery device
US5147654A (en) Oral osmotic device for delivering nicotine