U.S. patent application number 12/414815 was filed with the patent office on 2010-09-30 for methods and apparatus for dispensing medicaments into a punctal plug.
Invention is credited to Hassan Chaouk, Ken Church, Aruna Nathan, Phillip King Parnell, SR., Jason M. Tokarski, Michael J. Trezza, II.
Application Number | 20100243100 12/414815 |
Document ID | / |
Family ID | 42717098 |
Filed Date | 2010-09-30 |
United States Patent
Application |
20100243100 |
Kind Code |
A1 |
Tokarski; Jason M. ; et
al. |
September 30, 2010 |
METHODS AND APPARATUS FOR DISPENSING MEDICAMENTS INTO A PUNCTAL
PLUG
Abstract
This invention discloses methods and apparatus for providing a
dispensing a material with an active agent into an ophthalmic
device. Some embodiments include dispensing high viscous materials
into a punctal plug.
Inventors: |
Tokarski; Jason M.;
(Jacksonville, FL) ; Trezza, II; Michael J.;
(Great Meadows, NJ) ; Nathan; Aruna; (Bridgewater,
NJ) ; Chaouk; Hassan; (Jacksonville, FL) ;
Church; Ken; (Orlando, FL) ; Parnell, SR.; Phillip
King; (Jacksonville, FL) |
Correspondence
Address: |
PHILIP S. JOHNSON;JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
42717098 |
Appl. No.: |
12/414815 |
Filed: |
March 31, 2009 |
Current U.S.
Class: |
141/21 |
Current CPC
Class: |
B65B 3/003 20130101;
A61F 9/00772 20130101; A61J 3/00 20130101; A61K 9/0051
20130101 |
Class at
Publication: |
141/21 |
International
Class: |
B65B 3/12 20060101
B65B003/12 |
Claims
1. An apparatus for forming an ophthalmic device, the apparatus
comprising: a mount for receiving the ophthalmic device, wherein
the ophthalmic device comprises a cavity for containing an active
agent-containing material; a nozzle through which the excipient and
the active agent are dispensed into the cavity of the ophthalmic
device; and a pump for dispensing the excipient through the nozzle
into the cavity of the ophthalmic device.
2. The apparatus of claim 1, wherein the device is a punctal
plug.
3. The apparatus of claim 2, wherein the active agent-containing
material comprises poly(epsilon-caprolactone) and ethylene vinyl
acetate.
4. The apparatus of claim 3, wherein the poly(epsilon-caprolactone)
and ethylene vinyl acetate are each present in an amount of about
50 weight percent.
5. The apparatus of claim 1 or 3, wherein the active
agent-containing material comprises one or more fiber or fiber-like
structures.
6. The apparatus of claim 1 or 2, wherein the device further
comprises a release modulating component selected from the group
consisting of biodegradable semi-permeable membranes,
non-biodegradable semi-permeable membranes, pores and combinations
thereof.
7. The apparatus of claims 1 or 2, wherein the active-agent
containing material further comprises an outer segment comprising a
first material having a low concentration of the active agent and
an inner segment comprising a second material having a high
concentration of the active agent, wherein the permeability of the
first material to the active agent is less than the permeability of
the second material.
8. The apparatus of claim 2 wherein the active agent-containing
material further comprises one or more of a phase separated
inclusion, a destabilizing inclusion or a stabilizing
inclusion.
9. The apparatus of claim 2 wherein the pump comprises a positive
displacement pump.
10. The apparatus of claim 2 wherein the punctal plug comprises a
body having a first end and a second end; a surface extending
between the two ends; a reservoir contained within the body wherein
the reservoir comprises at least one opening, an active
agent-containing material and an active agent, wherein the active
agent is present in a continuous or discontinuous concentration
gradient within the active agent-containing material.
11. The apparatus of claim 2 additionally comprising a reservoir
for containing a volume of the active agent-containing material to
be dispensed.
12. The apparatus of claim 11 wherein the reservoir comprises a
syringe cartridge.
13. The apparatus of claim 12 wherein the syringe comprises
polycarbonate.
14. The apparatus of claim 11, additionally comprising a heater
device positioned to heat a volume of active agent-containing
material contained within the reservoir.
15. The apparatus of claim 2 additionally comprising a heater
device positioned to heat an active agent-containing material in
the nozzle.
16. The apparatus of claim 2 wherein the pump for dispensing the
active agent-containing material through the nozzle into the cavity
of the punctal plug is capable of dispensing a volume of material
of 50 picoliters of less.
17. The apparatus of claim 2 wherein the pump for dispensing the
active agent-containing material through the nozzle into the cavity
of the punctal plug is capable of dispensing a volume of material
with a viscosity comprising between 1 centipoise to 1,000,000
centipoise.
18. The apparatus of claim 2 wherein the pump for dispensing the
active agent-containing material through the nozzle into the cavity
of the punctal plug is capable of dispensing a volume of material
with a viscosity comprising between 500,000 centipoise to 3,500,000
centipoise.
Description
FIELD OF USE
[0001] This invention describes methods and apparatus for
dispensing one or more materials, such as a medicament, into a
punctal plug reservoir and, more specifically, in some embodiments,
dispensing a drug component including excipients into a cavity of a
punctal plug.
BACKGROUND
[0002] Medicaments frequently are administered to the eye for the
treatment of ocular diseases and disorders. Conventional means for
delivering medicaments to the eye involve topical application to
the surface of the eye. The eye is uniquely suited to topical
administration because, when properly constituted, topically
applied medicaments can penetrate through the cornea and rise to
therapeutic concentration levels inside the eye. Medicaments for
ocular diseases and disorders may be administered orally or by
injection, but such administration routes are disadvantageous in
that, in oral administration, the active agent may reach the eye in
too low a concentration to have the desired pharmacological effect
and their use is complicated by significant, systemic side effects
and injections pose the risk of infection.
[0003] The majority of ocular medicaments are currently delivered
topically using eye drops which, though effective for some
applications, are inefficient. When a drop of liquid is added to
the eye, it overfills the conjunctival sac, the pocket between the
eye and the lids, causing a substantial portion of the drop to be
lost due to overflow of the lid margin onto the cheek. In addition,
a substantial portion of the drop that remains on the ocular
surface is drained into the lacrimal puncta, diluting the
concentration of the drug.
[0004] Accordingly, alternative methods and devices for delivering
medicaments to an ophthalmic area may be beneficial.
SUMMARY
[0005] The present invention relates to devices for administering a
medicament via a punctal plug, and includes methods and apparatus
for deposition of a medicament in a punctal plug cavity wherein the
medicament can subsequently be delivered to a patient with the
punctal plug inserted into a punctum.
DESCRIPTION OF THE DRAWINGS
[0006] FIG. 1 illustrates a punctal plug and method for deposition
into a punctal plug according to some embodiments of the present
invention.
[0007] FIG. 2A illustrates apparatus for punctal plug deposition
according to some embodiments of the present invention.
[0008] FIG. 3 illustrates additional aspects of apparatus for
punctal plug deposition according to some embodiments of the
present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0009] The present invention includes apparatus and methods for
forming punctal plugs that may be used to deliver active agents to
one or both of the nasolacrimal duct and to the tear fluid of the
eye. In some embodiments, a location for dissemination of an active
agent is positioned to release the active agent into tear fluid and
preferably with minimal release into the nasolacrimal duct. Some
embodiments include apparatus and methods for forming a punctal
plug comprising, consisting essentially of, and consisting of: a
punctal plug body having a first end and a second end; a surface
extending between the two ends; a reservoir contained within the
punctal plug body wherein the reservoir comprises, consists
essentially of and consists of an active agent-containing material
and an active agent, wherein the active agent is present in a
continuous or discontinuous concentration gradient within the
active agent-containing material. The punctal plug may additionally
comprise a defined area, such as an opening in the punctal plug,
which is more conducive to elution or other dissemination of the
active agent from the punctal plug cavity to an area proximate to
the punctal plug. Some preferred embodiments include an area
conducive to dissemination of the active agent comprising an
opening with a diameter which is smaller than a diameter of the
cavity containing the active ingredient.
[0010] The present invention additionally provides devices, and
methods for their use and manufacture, that can be used to deliver
active agents into a cavity in a punctal plug in a controlled
manner.
[0011] It has been known to fill a cavity in a punctal plug via
insertion of a rod, or other rigid or semi rigid article. The rod
can include a pharmaceutical or other medicament. However, the
physical conditions of a punctum may include physical manipulation
and the presence of moisture. Insertion of a rod of medicament into
a plug can be difficult.
[0012] Definitions:
[0013] As used herein, the term "active agent" refers to an agent
capable of treating, inhibiting, or preventing a disorder or a
disease. Exemplary active agents include, without limitation,
pharmaceuticals and nutraceuticals. Preferred active agents are
capable of treating, inhibiting, or preventing a disorder or a
disease of one or more of the eye, nose and throat.
[0014] As used herein, the term "punctal plug" refers to a device
of a size and shape suitable for insertion into the inferior or
superior lacrimal canaliculus of the eye through, respectively, the
inferior or superior lacrimal punctum.
[0015] As used herein, the term "opening" refers to an opening in
the punctal plug body of a device of the invention of a size and
shape through which the active agent can pass. Preferably, only the
active agent can pass through the opening. The opening may be
covered with a membrane, mesh, grid or it may be uncovered. The
membrane, mesh, or grid may be one or more of porous, semi-porous,
permeable, semi-permeable, and biodegradable.
[0016] Referring now to FIG. 1, at 1A a punctal plug device 101 is
illustrated with an opening 102 which fluidly communicates with a
cavity 105 formed in the punctal plug body. At 1B, a dispenser tip
103 is positioned proximate to the opening 102 and dispenses a
material 104 through the opening 102 and into the cavity 105. At
1C, the cavity 105 is shown filled by the dispenser tip 103 with a
material 104 containing an active agent. Examples of active agents
can include one or more of: bimatoprost; bimatoprost with an
ethyleneoxynalacetate ("EVA") membrane in amounts greater than 0
and less than 25%.
[0017] In various embodiments of the present invention, the
material 104 containing one or more active agents-and an active
agent therein is deposited in the cavity 105 of a punctal plug
device in small doses and at high viscosity. For example, in some
embodiments, the material 104 can have a viscosity of between 1
(one) centipoise to over 1,000,000 (one million) centipoise. In
addition, some embodiments include deposition of small doses of the
material 104, such as between 10 (ten) picoliters and 10,000 (ten
thousand) picoliters. The material 104 may also include one or more
excipients. The excipients may be the portion of the material 104
which provides the high viscous properties.
[0018] The cavity may be any size and/or shape that a punctal plug
design may support. In some embodiments, the volume of the cavity
105 will be about between 10 and 100 nanoliters. Some specific
embodiments include a cavity volume of about between 40 nanoliters
and 50 nanoliters. An opening 102 to a cavity into which a
dispenser tip may be inserted, may be, for example, include a
diameter of between about 0.1 mm to 0.4 mm and a cavity 105 may
include a depth of between about 0.5 mm to about 2.0 mm. In some
preferred embodiments, the opening 102 will be about 0.2 mm and the
depth of the cavity will be about 1.5 mm. Additional preferred
aspects of embodiments can include a design with a 0.385 diameter
and 1.5 mm length with a cavity volume of 175 nL.
[0019] The active agent may be dispersed throughout the active
agent-containing material 104 or dissolved within the material 104.
Alternatively, the active agent may be contained in inclusions,
particulates, droplets, or micro-encapsulated within the material
104. Still as another alternative, the active agent may be
covalently bonded to the material 104 and released by hydrolysis,
enzymatic degradation and the like. Yet as another alternative, the
active agent may be in a reservoir within the material 104.
[0020] According to some embodiments of the present invention the
active agent may be released from the punctal plug device 101 in a
controlled manner, meaning over a period of time by using an active
agent-containing material 104 in which the agent is present in a
continuous concentration gradient throughout the material 104 or by
using a discontinuous concentration gradient. Additional
embodiments include a device that exhibits a "burst" or immediate
release upon insertion of an amount of active agent that is greater
than the average release rate over time.
[0021] Referring now to FIG. 2, an example of some embodiments of
the present invention which include a punctal plug active agent
pump 200 for depositing the material with an active ingredient 104
into a cavity 105 of a punctal plug device 101 (illustrated in FIG.
1). Generally, the pump 200 includes a reservoir, such as a
cartridge 201, mounted in a pump body 207 and attached to provide
fluid communication to a dispenser tip 203. The cartridge 201 can
include, for example, a removable syringe.
[0022] The cartridge 201 can be formed from a polycarbonate,
stainless steel or other rigid or semi-rigid material. In some
preferred embodiments, the cartridge is formed from a material that
can be sterilized and also withstand heating during the deposition
process. Additionally, in some embodiments, the cartridge 201 will
have an end proximate to the dispenser tip 203 and an end distal to
the dispenser tip, wherein the end proximate to the dispenser tip
can include a lure lock mechanism for securing the cartridge 201 to
a dispenser body 202. Other locking or fastening mechanisms may
also be used to secured the cartridge 201 in a position proximate
to and in fluid communication with the dispenser tip 203. Some
embodiments may therefore include designs of a polycarbonate or
stainless steel syringe.
[0023] Some embodiments can include a "smart pump" such as a
positive pressure pump with a computer controlled needle valve,
which control starts and stops and material flow for a range of
viscosities. A computer controlled needle valve provides active
valving to control flow characteristics, such as, for example:
opening, closing and suck-back associated with the pumping of the
active agent-containing material 104. A dead volume inside the pump
can range in some embodiments from between about 0.025 cc to 0.3
cc. Such degrees of control, allow the present invention to
dispense very small volumes of an active agent-containing material
104. Some embodiments can include dispensing volumes of 50
picoliters or less and in some preferred embodiments, volumes of
between 20 picoliters to 60 picoliters. In another aspect, a range
of viscosities of an active agent-containing material 104 from 1
centipoise to over 1,000,000 centipoise. Other embodiments include
a range of viscosities of between 500,000 centipoise to 3,500,000
centipoise. One exemplary pump mechanism can include a high
pressure positive displacement pump, such as those offered for
commercial use by nScript, Inc.
[0024] Some preferred embodiments will include one or more heating
sources 204-206 for heating the material with an active ingredient
104 while it is in one or more of: a) the cartridge 201; b) the
dispenser body 202; and c) the dispenser tip 203. The heat source
can include, for example, one or more of: electrically resistive
elements; thermoelectric devices and heated fluid paths. As
illustrated, in some embodiments, a heating source 205 may be
located along side the cartridge 201 and allow the material with an
active ingredient 104 to be kept at an elevated temperature while
in the cartridge 201. Some embodiments can also include a heater
element 204 in or proximate to the pump body 207. Some embodiments
may also include temperature requirements that may be adjusted
according to material properties excipients to be deposited.
[0025] In another aspect, some embodiments of the present invention
include a temperature probe 206. The temperature probe can include
a transducer for providing a digital or analog output indicating a
temperature of a designated portion of the punctal plug active
agent pump 200. Embodiments can include an electronic feedback
circuit (not shown), which allows control of an amount of heat
applied to the active ingredient 104. In some embodiments, the
feedback constitutes a closed loop feedback design.
[0026] Additionally, in some embodiments, an amount of heat applied
to the material containing an active ingredient 104 can be used to
control a viscosity of the material containing an active ingredient
104. Typically, a higher amount of heat applied will lower the
viscosity of the material containing an active ingredient 104 and
allow for less pressure to be applied to move the material
containing an active ingredient 104 through the punctal plug active
agent pump 200. By way of example, a material containing an active
ingredient 104 can be dispensed through the dispenser tip 203 at a
temperature of between 40.degree. C. and 80.degree. C. and in some
preferred embodiments at a temperature of between 60.degree. C. and
70.degree. C. In some particular embodiments, a punctal plug 101
into which the material containing the active material 104 is
dispensed is also heated to a temperature of between 40.degree. C.
and 80.degree. C. In some embodiments, the application of heat to
the punctal plug 101 can provide additionally elasticity to the
plug during the deposition allowing the cavity 105 to expand and
more easily accept the material containing an active ingredient
104. In various embodiments, a preferred temperature may be based
upon one or more of: an active ingredient used; an excipient
included in the material containing an active ingredient 104;
and
[0027] Referring now to FIG. 3, a perspective view illustrates a
pump 200 with a dispenser tip 301 and a quick change tip base 302.
The quick change tip base facilitates removal/replacement of a tip
by an operator. As illustrated in FIG. 3, in some embodiments, pump
body 304 can be mounted on a track 304, or other mechanical or
robotic device which allows motion in one, two or three dimensions.
The motion may be controlled in some embodiments, motion is
controlled via automation and allows for the alignment of the
dispenser tip 301 with a punctal plug (not illustrated in FIG. 3).
In still another aspect, some embodiments may include a automated
vision system to facilitate automated alignment and filling of
plugs.
[0028] Without being bound to any particular theory, it is believed
that an active agent-containing material 104 that does not undergo
significant chemical degradation during the time desired for the
release of active agent will release the agent by diffusion through
the matrix to a device's release surfaces, meaning surfaces of the
active agent-containing material 104 in contact with a person's
body fluid. According to Fick's Law, the diffusive transport or
flux, J, of the agent through the active agent-containing material
104 is governed at each point and each time by the local
concentration gradient, the diffusivity of the active agent with
the material D, and the spatial variation of the cross-sectional
geometry of the device.
[0029] Some exemplary embodiments can include a material with a mix
of excipients and active agents. Pre-mixing apparatus and processes
may include twin-screw compounding, chaotic mixing, solvent mixing,
or spray drying, or other mixing mechanisms. An exemplary compound
can include: 25% bimatoprost as an active agent; 37.5% ethylene
vinyl acetate, EVA as a first excipient and 37.5% polycaprolactone,
PCL as a second excipient.
[0030] The pre-mixed material can be loaded into the heated or
non-heated syringe 200 as pellets. Pellets are not a requirement;
the material 104 can be in the form of one or more of: a powder,
fluff and other mediums. Additionally, in some embodiments, such as
those in which it is desired to avoid multiple thermal cycle
exposure of an active agent and/or to minimize air bubbles, the
heated syringe may be directly attached to the micro-compounder so
that the pre-mixed material is directly supplied into a nano-dosing
dispensing system, such as those described above, without having to
cool it to room temperature or lower. As such, in some embodiments
the material containing an active agent may be supplied to the
nano-dispensing system in a melt form.
[0031] In another aspect of the present invention, a local gradient
of a concentration of active agent may be controlled by placing
more active agent at one location in the material containing an
active agent 104 relative to another location. Alternatively, the
matrix may be have a gradient, meaning that one section of the
material 104 has a first concentration and the concentration
abruptly changes to a second, different concentration in an
adjacent section of the matrix. The diffusivity for the active
agent may also be spatially controlled by varying one or more of
the chemical composition, porosity, and crystallinity of the active
agent-containing material 104.
[0032] Additionally, the spatial variation of the material's
cross-sectional geometry may be used to control diffusivity. For
example, if the material 104 was in the form of a straight rod that
has a uniform active agent concentration, diffusivity will be
reduced when the area at the open end of the material 104 is
significantly smaller than the average of the entire material 104.
Preferably, the material 104 area at the open end of the device is
no more than one-half of the average cross sectional area of the
material, meaning the cross section determined perpendicular to the
primary dimension of active agent transport use.
[0033] One of ordinary skill in the art will recognize that,
depending on how one varies one or more of the local concentration
gradient, the diffusivity of the active agent from the material D,
and the spatial variation of the cross-sectional geometry of the
device, a variety of release profiles may be obtained including,
without limitation first order, second order, biphasic, pulsatile
and the like. For example, either or both of the active agent
concentration and diffusivity may increase from the surface to the
center of the active agent-containing material in order to achieve
more initial release. Alternatively, either or both may be
increased or decreased and then increased again within the material
to achieve a pulsatile release profile. The ability to achieve a
variety of release profiles by varying local concentration
gradient, the diffusivity of the active agent, and the spatial
variation of the cross-sectional geometry may eliminate the need
for rate-limiting membranes in the device.
[0034] Devices formed according to the present invention may
contain a reservoir or cavity 104 within the punctal plug body, and
the cavity 104 has at least at least one active agent-containing
material deposited therein. In some embodiments, the punctal plug
body is preferably impermeable to the active agent, meaning only an
insubstantial amount of active agent can pass there through, and
the punctal plug body has at least one opening through which the
active agent is released. The opening may have a membrane or
permeable material covering through which the active agent may pass
in therapeutic amounts.
[0035] The active agent-containing material useful in the devices
of the invention is any material that is capable of containing the
active agent, does not alter the chemical characteristics of the
active agent, and does not significantly chemically degrade or
physically dissolve when placed in contact with ocular fluids.
Preferably, the active agent-containing material is
non-biodegradable, meaning that it does not degrade to a
substantial degree upon exposure to biologically active substances
typically present in mammals. Additionally, the active
agent-containing material is capable of releasing the active agent
by one or more of diffusion, degradation, or hydrolyzation.
Preferably, the active agent-containing material is a polymeric
material, meaning that it is a material made of one or more types
of polymers.
[0036] When the active agent-containing material is combined with
the active agent, the material may also contain one or more
materials that are insoluble in water and non-biodegradable, but
from which the active agent can diffuse. For example, if the active
agent-containing material is a polymeric material, the material may
be composed of one or more polymers that are insoluble in water and
non-biodegradable.
[0037] Suitable polymeric materials for the active agent-containing
material include, without limitation, hydrophobic and hydrophilic
absorbable and non-absorbable polymers. Suitable hydrophobic,
non-absorbable polymers include, without limitation, ethylene vinyl
alcohol ("EVA"), fluorinated polymers including without limitation,
polytetrafluoroethylene ("PTFE") and polyvinylidene fluoride
("PVDF"), polypropylene, polyethylene, polyisobutylene, nylon,
polyurethanes, polyacrylates and methacrylates, polyvinyl
palmitate, polyvinyl stearates, polyvinyl myristate,
cyanoacrylates, epoxies, silicones, copolymers thereof with
hydrophobic or hydrophilic monomers, and blends thereof with
hydrophilic or hydrophobic polymers and excipients.
[0038] Hydrophilic, non-absorbable polymers useful in the invention
include, without limitation, cross-linked poly(ethylene glycol),
poly(ethylene oxide), poly(propylene glycol), poly(vinyl alcohol),
poly(hydroxyethyl acrylate or methacrylate),
poly(vinylpyrrolidone), polyacrylic acid, poly(ethyloxazoline), and
poly(dimethyl acrylamide), copolymers thereof with hydrophobic or
hydrophilic monomers, and blends thereof with hydrophilic or
hydrophobic polymers and excipients.
[0039] Hydrophobic, absorbable polymers that may be used include,
without limitation, aliphatic polyesters, polyesters derived from
fatty acids, poly(amino acids), poly(ether-esters), poly(ester
amides), polyalkylene oxalates, polyamides, poly(iminocarbonates),
polycarbonates, polyorthoesteres, polyoxaesters, polyamidoesters,
polyoxaesters containing amine groups, phosphoesters,
poly)anhydrides), polypropylene fumarates, polyphosphazenes, and
blends thereof. Examples of useful hydrophilic, absorbable polymers
include, without limitation, polysaccharides and carbohydrates
including, without limitation, crosslinked alginate, hyaluronic
acid, dextran, pectin, hydroxyethyl cellulose, hydroxy propyl
cellulose, gellan gum, guar gum, keratin sulfate, chondroitin
sulfate, dermatan sulfate, proteins including, without limitation,
collagen, gelatin, fibrin, albumin and ovalbumin, and phospholipids
including, without limitation, phosphoryl choline derivatives and
polysulfobetains.
[0040] More preferably, the active agent-containing material is a
polymeric material that is polycaprolactone. Still more preferably,
the material is poly(epsilon-caprolactone), and ethylene vinyl
acetate of molecular weights between about 10,000 and 80,0000.
About 0 to about 100 weight percent polycaprolactone and about 100
to about 0 weight percent of the ethylene vinyl acetate are used
based on the total weight of the polymeric material and,
preferably, about 50% each of polycaprolactone and ethylene vinyl
acetate is used.
[0041] The polymeric material used is preferably greater than about
99% pure and the active agents are preferably greater than about
97% pure. One of ordinary skill in the art will recognize that in
compounding, the conditions under which compounding is carried out
will need to take into account the characteristics of the active
agent to ensure that the active agents do not become degraded by
the process. The polycaprolactone and ethylene vinyl acetate
preferably are combined with the desired active agent or agents,
micro-compounded, and then extruded.
[0042] In a preferred embodiment, the active agent-containing
material is a polymeric material that is combined with at least one
active agent to form a highly viscous material, such as, for
example with a viscosity of between 500,000 cP and 4,000,000 cP.
Preferably the viscosity of the active agent containing material
can be decreased by heating the active agent containing material
while it is contained in, or passing through a dispensing pump
according to the present invention.
Conclusion
[0043] The present invention, as described above and as further
defined by the claims below, provides methods of processing punctal
plugs and apparatus for implementing such methods, as well as
punctal plugs formed thereby.
* * * * *