U.S. patent number RE44,459 [Application Number 13/410,973] was granted by the patent office on 2013-08-27 for method for lowering blood glucose.
This patent grant is currently assigned to Alza Corporation. The grantee listed for this patent is Atul Devdatt Ayer, Anthony L. Kuczynski, Patrick S. L. Wong. Invention is credited to Atul Devdatt Ayer, Anthony L. Kuczynski, Patrick S. L. Wong.
United States Patent |
RE44,459 |
Kuczynski , et al. |
August 27, 2013 |
Method for lowering blood glucose
Abstract
The invention disclosed comprises a method for administering the
antidiabetic drug glipizide to a patient in need of glipizide in
need of antidiabetic therapy.
Inventors: |
Kuczynski; Anthony L. (Mountain
View, CA), Ayer; Atul Devdatt (Palo Alto, CA), Wong;
Patrick S. L. (Palo Alto, CA) |
Applicant: |
Name |
City |
State |
Country |
Type |
Kuczynski; Anthony L.
Ayer; Atul Devdatt
Wong; Patrick S. L. |
Mountain View
Palo Alto
Palo Alto |
CA
CA
CA |
US
US
US |
|
|
Assignee: |
Alza Corporation (Vacaville,
CA)
|
Family
ID: |
46276115 |
Appl.
No.: |
13/410,973 |
Filed: |
March 2, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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10131916 |
Apr 25, 2002 |
|
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|
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07650822 |
Jan 22, 1991 |
5545413 |
|
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07402314 |
Sep 5, 1989 |
5024843 |
|
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Reissue of: |
08180409 |
Jan 11, 1994 |
6361795 |
Mar 26, 2002 |
|
|
Current U.S.
Class: |
424/484; 424/488;
424/468; 424/473; 514/866; 424/469 |
Current CPC
Class: |
A61P
3/10 (20180101); A61K 31/64 (20130101); A61K
9/0004 (20130101); A61K 9/2054 (20130101); Y10S
514/866 (20130101); A61K 9/2027 (20130101); A61K
9/2031 (20130101) |
Current International
Class: |
A61K
9/22 (20060101); A61K 9/26 (20060101); A61K
9/36 (20060101) |
Field of
Search: |
;424/484,488,468,469,473
;514/866 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Martindale, The Extra Pharmacopoeia, 29th Ed. (1989) p. 390. cited
by applicant .
AHF Drug Information, (1989) pp. 1741-1745. cited by applicant
.
J. Am. Phar. Assoc., Sci. Ed., vol. 48 (1959) pp. 451-459. cited by
applicant .
J. Am. Phar. Assoc., Sci. Ed., vol. 49 (1960) pp. 82-84. cited by
applicant .
Remington's Pharmaceutical Sciences, 14th Ed., (1970) pp.
1626-1678. cited by applicant.
|
Primary Examiner: Haghighatian; Mina
Attorney, Agent or Firm: Woodcock Washburn LLP
Parent Case Text
CROSS-REFERENCE TO CO-PENDING APPLICATION
.Iadd.Notice: More than one reissue application has been filed for
the reissue of U.S. Pat. No. 6,361,795. This application a
continuation of U.S. Ser. No. 10/131,916, filed Apr. 25, 2002 (now
abandoned), which was filed as a reissue of U.S. Pat. No.
6,361,795, issued Mar. 26, 2002. .Iaddend.
This application is a continuation-in-part of U.S. Appln. Ser. No.
07/650,822 filed Jan. 22, 1991, now U.S. Pat. 5,545,413 which Ser.
No. 07/650,822 is a division of U.S. Appln. Ser. No. 07/402,314,
filed Sep. 5, 1989 which Ser. No. 07/402,314 now is U.S. Pat. No.
5,024,843 issued Jun. 18, 1991, and was with U.S. Ser. No.
07/652,717 now U.S. Pat. No. 5,091,190 issued Feb. 25, 1992, and
benefit of these filing dates is claimed herein.
Claims
We claim:
.[.1. A method for treating hyperglycemia in a patient, wherein the
method comprises administering to the patient a dosage form
comprising 2.0 mg to 750 mg of a glipizide composition that is
administered at a dose of 10 ng to 25 mg per hour over an extended
period of 24 hours, and wherein the method is characterized by
administering the glipizide from a dosage form selected from the
group consisting of an osmotic dosage form comprising a
semipermeable polymer permeable to the passage of fluid, and a
diffusion dosage form comprising a polymer that permits diffusion
of glipizide through the polymer..].
.[.2. A method for lowering blood sugar in the treatment of a
diabetic patient, which method comprises orally administering to
the patient an effective blood sugar lowering dose of a composition
comprising glipizide and a pharmaceutically acceptable carrier,
which blood sugar lowering dose is administered by a method
selected from the group consisting of osmosis comprising a
semipermeable membrane, diffusion through a polymer permeable to
glipizide, and ion-exchange over time to produce the intended
lowering of the blood sugar in the patient..].
.Iadd.3. A method for treating hyperglycemia in a patient, wherein
the method comprises orally administering to the patient a
once-a-day dosage form comprising 2.0 mg to 50 mg of a glipizide
composition and wherein the method is characterized by
administering the glipizide from an osmotic dosage form comprising
polyethylene oxide, hydroxypropylmethylcellulose, cellulose
acetate, and sodium chloride. .Iaddend.
Description
DISCLOSURE OF TECHNICAL FIELD
This invention pertains to dosage forms comprising the drug
glipizide. The invention relates also to compositions comprising
glipizide, and the invention concerns additionally a method for
administering glipizide to a patient in need of glipizide
therapy.
DISCLOSURE OF BACKGROUND OF THE INVENTION
A clinical need exists for a dosage form and for a method for
delivering an oral blood-glucose lowering drug to a patient needing
this therapy. Glipizide is an oral blood-glucose lowering drug and
it is indicated for the control of hyperglycemia and its associated
symptomatology in patients with non-insulin dependent diabetes
mellitus. Glipizide is useful therapeutically as an oral
hypoglycemic drug because it stimulates insulin secretion from the
beta cells of pancreatic-islet tissue, it increases the
concentration of insulin in the pancreatic vein, and because it
exhibits extrapancreatic action such as the ability to increase the
number of insulin receptors.
Glipizide is known chemically as N-[2-[4-[[[(cyclohexylamino)
carbonyl]amino]sulfonyl]phenyl] ethyl]-5-methylpyrazinecarboxamide.
Glipizide is a white, odorless powder with a pKa of 5.9, and it is
insoluble in both water and alcohol. These physical and chemical
properties of glipizide do not lend the drug to formulation into a
dosage form, and these properties do not lead to a method, that in
both instances that can administer glipizide at a controlled and
known rate per unit time to produce the intended therapy. The
properties of glipizide are disclosed in Martindale The Extra
Pharmacopoeia, 29th Ed., p 390, (1989); and, AHFS Drug Information,
pp 1741-45, (1989).
In the light of the above presentation, it will be appreciated by
those versed in the medical and in this pharmaceutical dispensing
art to which this invention pertains, that a pressing need exists
for dosage forms that can deliver the valuable drug glipizide in a
rate-controlled dose to a patient in clinical need of blood-glucose
lowering therapy. The pressing need exists also for an oral dosage
form and for a method of therapy that can deliver glipizide at a
controlled rate in a substantially constant dose per unit time for
its beneficial therapeutic effects, and remain substantially
independent of the changing environment of the gastrointestinal
tract. It will be appreciated further by those skilled in the
dispensing art, that if such a novel and unique dosage form and
method is made available that can administer glipizide in a
rate-controlled dose over time, and simultaneously provide a method
of blood-glucose lowering therapy, the dosage form and the
accompanying method would represent an advancement and a valuable
contribution to the medical art.
DISCLOSURE OF OBJECTS OF THE INVENTION
Accordingly, in view of the above presentation, it is an immediate
object of this invention to provide a dosage form for delivering
glipizide in a rate controlled amount, and which dosage form
substantially overcomes the deficiencies and omissions associated
with the prior art.
Another object of the present invention is to provide a dosage form
for orally administering glipizide in a rate-controlled dose for
blood-glucose lowering therapy.
Another object of the invention is to provide a pharmaceutical
dosage form that makes available controlled and sustained glipizide
therapeutic activity to a patient in need of glipizide therapy.
Another object of the invention is to provide a novel dosage form
manufactured as an osmotic, diffusional, bioerodible or
ion-exchange device that can administer glipizide to a biological
receptor site to produce the desired glipizide pharmacological
effects.
Another object of the present invention is to provide a dosage form
manufactured as an osmotic, diffusional, bioerodible, or
ion-exchange dosage form that maintains glipizide in the dosage
form until released from the dosage form, thereby substantially
reducing and/or substantially eliminating the unwanted influences
of the gastrointestinal environment of use and still provide
controlled administration of glipizide over time.
Another object of the present invention is to provide a dosage form
that can deliver the substantially aqueous insoluble drug glipizide
at a controlled and beneficial known rate over time.
Another object of the present invention is to provide a dosage form
adapted for the oral administration of glipizide and which dosage
form comprise a first composition and a contacting second
composition that operate in combination for the controlled
administration of glipizide.
Another object of the present invention is to provide a complete
pharmaceutical glipizide regimen comprising a composition
comprising glipizide that can be dispensed from a drug delivery
dosage form, the use of which requires intervention only for
initiation and possibly for termination of the regimen.
Another object of the invention is to provide a method for treating
hyperglycemia by orally administering glipizide in a
rate-controlled dose per unit time to a warm-blooded animal in need
of hyperglycemia therapy.
Another object of the invention is to provide a method that engages
osmotic, diffusional, bioerodible, or ion-exchange delivery for
administering glipizide in a therapeutic dose per unit time or an
extended time to a human patient in need of glipizide therapy.
Other objects, features and advantages of this invention will be
more apparent to those versed in the dispensing arts from the
following detailed specification, taken in conjunction with the
drawings and the accompanying claims.
BRIEF DISCLOSURE OF THE DRAWINGS
In the drawings, which are not drawn to scale, but are set forth to
illustrate various embodiments of the invention, the drawing
figures are as follows:
Drawing FIG. 1 is a view of one dosage form provided by the
invention designed and shaped for orally administering glipizide to
the gastrointestinal tract of a warm-blooded animal, including
humans;
Drawing FIG. 2 is an opened view of a dosage form of drawing FIG. 1
illustrating the structure of the dosage form comprising
glipizide;
Drawing FIG. 3 is an opened view of the dosage form of drawing FIG.
1 depicting a different internal structure embodiment provided by
the invention;
Drawing FIG. 4 is a graph that depicts the release rate pattern
from one embodiment of the dosage form provided by the method of
the invention that administers glipizide at a rate-controlled by
the dosage form over an extended period of therapy; and,
Drawing FIG. 5 is a graph that depicts the release rate pattern for
a different embodiment of the dosage form provided by the
invention, wherein the glipizide is administered by a method
employing an osmotic, diffusional, bioerodible, or ion-exchange
dosage form.
In the drawing figures and in the specification like parts in
related drawing figures are identified by like numbers. The terms
appearing earlier in the specification and in the description of
the drawings, as well as embodiments thereof, are further described
elsewhere in the disclosure.
DETAILED DISCLOSURE OF THE DRAWING FIGURES
Turning now to the drawing figures in detail, which drawing figures
are examples of the dosage forms provided by this invention, and
which examples are not to be construed as limiting, one example of
the dosage form is illustrated in drawing FIG. 1 and designated by
the numeral 10. In drawing FIG. 1, dosage form 10 comprises a body
11, which body member 11 comprises a wall 12 that surrounds and
encloses an internal compartment, not seen in drawing FIG. 1.
Dosage form 10 comprises at least one exit means 13 for connecting
the interior of dosage form 10 with the exterior environment of
use.
In drawing FIG. 2, dosage form 10 is seen in opened view. In
drawing FIG. 2, dosage form 10 comprises a body member 11
comprising wall 12, which wall surrounds and defines an internal
compartment 14. Wall 12 comprises at least one exit means 13 that
connects internal compartment 14 with the exterior of dosage form
10. Dosage form 10 can comprise more than one exit means 13. Wall
12 of dosage form 10 comprises in total, or in at least a part, a
composition that is permeable to the passage of an exterior fluid
present in the environment, and wall 12 is substantially
impermeable to the passage of glipizide and other ingredients
present in compartment 14. The composition comprising wall 12 is
semipermeable, it is substantially inert, and wall 12 maintains its
physical and chemical integrity during the dispensing life of
glipizide from dosage form 10. The phrase, "keeps its physical and
chemical integrity," means wall 12 does not lose its structure, and
it does not change chemically during the glipizide dispensing life
of dosage form 10.
Wall 12, in a present embodiment, comprises 60 weight percent (wt
%) to 100 weight percent of a composition comprising a cellulose
polymer. The cellulose polymer comprises a member selected from the
group consisting of a cellulose ester, cellulose ether, cellulose
ester-ether, cellulose acylate, cellulose diacylate, cellulose
triacylate, cellulose acetate, cellulose diacetate, and cellulose
triacetate. Wall 12, in another manufacture, comprises from 0
weight percent to 25 weight percent of a member selected from the
group consisting of hydroxyalkylcellulose,
hydroxypropylalkylcellulose, hydroxypropylcellulose, and
hydroxypropylmethylcellulose, and from 0 to 20 weight percent of
polyethylene glycol, with the total amount of all wall-forming
components comprising wall 12 equal to 100 weight percent.
Internal compartment 14 in one dosage form comprises an internal
glipizide lamina 15, which glipizide lamina can be defined as
glipizide composition 15. Internal compartment 14 also comprises an
internal displacement lamina 16, which displacement lamina can be
defined as displacement composition 16. The glipizide lamina 15 and
the displacement lamina 16 initially are in laminar arrangement and
they cooperate with each other and with dosage form 10 for the
effective delivery of glipizide from dosage form 10.
The glipizide composition 15, in a present embodiment, as seen in
FIG. 2, comprises about 2.0 mg to 750 mg of glipizide identified by
dots 9; from 100 mg to 320 mg of a polyethylene oxide comprising
80,000 to 350,000 molecular weight identified by dashes 17; from 5
mg to 50 mg of hydroxypropylmethylcellulose comprising a 9,200 to
22,000 molecular weight identified by vertical lines 18; and from 0
mg to 7.5 mg of a lubricant such as stearic acid, magnesium
stearate, and the like.
The displacement lamina 16, as seen in drawing FIG. 2, comprises 70
mg to 125 mg of a polyethylene oxide comprising a 4,000,000 to
8,000,000 molecular weight identified as lines 19; from 20 mg to 50
mg of an osmagent selected from the group consisting of sodium
chloride and potassium chloride identified by wavy line 20; and
from 5 mg to 15 mg of a hydroxypropylmethylcellulose having a 9,000
to 25,000 molecular weight identified by vertical slashes 21.
Displacement lamina 16 optionally comprises from 0.1 mg to 5 mg of
ferric oxide and from 0.01 mg to 5 mg of a lubricant such as
magnesium stearate or stearic acid.
Dosage form 10, in another manufacture the internal compartment 14
comprises a homogenous composition comprising 2.0 mg to 750 mg of
glipizide and an osmagent that exhibits an osmotic pressure
gradient across semipermeable wall 12 against an external aqueous
or biological fluid. The osmagents are known also as osmotically
effective solute and as osmotically effective compound. The amount
of osmagent is 1 mg to 350 mg for providing the composition
comprising glipizide. The osmagent operable for the purpose of this
dosage form comprises a member selected from the group consisting
of water-soluble inorganic salts, water soluble sugars, organic
osmagents and organic salts. Representative osmagents include
sodium chloride, potassium chloride, potassium acid phosphate,
tartaric acid, citric acid, raffinose, magnesium sulfate, magnesium
chloride, urea, inositol, sucrose, glucose, and sorbitol. Osmagents
are known in U.S. Pat. No. 4,783,332.
Drawing FIG. 3 depicts in opened section another dosage form 10
provided by the invention. In drawing FIG. 3, dosage form 10
comprises a body 11, a wall 12, which wall 12 surrounds an internal
compartment 14 with an exit passageway 13 in wall 12. Internal
compartment 14, in this dosage form, comprises an internal
glipizide lamina 15, which glipizide lamina 15 comprises 2 mg to
225 mg of aqueous insoluble drug glipizide identified by dots 9;
from 100 mg to 250 mg of a hydroxypropylcellulose comprising a
40,000 to 80,000 molecular weight identified by angle 22; and from
40 mg to 70 mg of a polyvinylpyrrolidone comprising a 30,000 to
70,000 molecular weight and identified by half circle 23. Internal
compartment 14 comprises a displacement lamina 16 comprising 30 mg
to 150 mg of sodium carboxymethylcellulose having 200,000 to
1,000,000 molecular weight identified by wavy lines 24; from 20 mg
to 70 mg of an osmagent selected from the group consisting of
osmogent sodium chloride, and potassium chloride identified by
circle 25; and from 0.5 mg to 10 mg of a
hydroxypropylmethylcellulose comprising a 9,200 to 22,000 molecular
weight identified by squares 26. Displacement lamina 16 optionally
comprises from 0 mg to 5 mg of ferric oxide and optionally 0 mg to
7 mg of a lubricant.
The expression, "exit means 13," as used herein, comprises means
and methods suitable for the controlled metered release of
glipizide 9 from compartment 14 of dosage form 10. The exit means
13 comprises at least one passageway, orifice, or the like, through
wall 12 for communication with glipizide 9 in compartment 14. The
expression, "at least one passageway," includes aperture, orifice,
bore, pore, or porous element through which glipizide can be
released, or hollow fiber, capillary tube, porous overlay, porous
insert, and the like. The expression also includes a material that
erodes or is fluid-leached from wall 12 in a fluid environment of
use to produce at least one pore-passageway of governed release
rate pore-size in wall 12. Representative materials suitable for
forming at least one passageway, or a multiplicity of passageways,
comprise an erodible polyglycolic acid, or a polylactic acid member
in wall 12, a gelatinous filament, polyvinyl alcohol, leachable
materials such as a fluid removable pore forming polysaccharide,
salt, oxide, polyol, or the like. A passageway or a plurality of
passageways can be formed by leaching a material such as sorbitol,
lactose, or the like, from wall 12. The passageway can have any
shape such as round, triangular, square, elliptical, and the like,
for assisting in the metered release of glipizide 9 from dosage
form 10. Dosage form 10 can be constructed with one or more
passageways in spaced apart relations, or more than one passageway
on a single surface of dosage form 10. Passageways and equipment
for forming passageways are disclosed in U.S. Pat. No. 3,845,770
issued November 1974 to Theeuwes et al; U.S. Pat. No. 3,916,899
issued November 1975 to Theeuwes et al; U.S. Pat. No. 4,016,880
issued April 1977 to Theeuwes et al; U.S. Pat. No. 4,063,064 issued
December 1977 to Saunders et al; U.S. Pat. No. 4,088,864 issued May
1978 to Theeuwes et al; and, passageways formed by leaching are
disclosed in U.S. Pat. Nos. 4,200,098 issued April 1980 to Ayer et
al; U.S. Pat. No. 4,235,236 issued November 1980 to Theeuwes; and,
U.S. Pat. No. 4,285,987 issued to Ayer et al.
Dosage form 10 used for the purpose of the invention includes also
dosage forms 10 that mediate the efficiency of glipizide by
imparting enhanced therapy from administering glipizide by the
method of the invention. Dosage forms 10 contemplated by the
invention also comprise a dosage form selected from the group
consisting of a bioerodiable-mediated dosage form,
diffusion-mediated dosage form and ion-exchange mediated dosage
form.
The bioerable-mediated dosage form 10 comprises a bioerodable
polymer matrix containing glipizide. Dosage form 10 provides a
mediated-release rate of glipizide delivered to a glipizide-drug
receptor as the polymer matrix bioerodes at a release-rate
controlled by the bioeroding matrix over time. Bioerodable polymers
for forming the dosage form containing glipizide include a member
selected from the group consisting of poly(ester) poly(amine), poly
(lactide), poly(glycolide), poly(lactide-co-glycolide), poly
(caprolactone), poly(hydroxybutyric acid), poly(orthoester),
poly(orthocarbonate), poly(acetal), poly(carbohydrate),
poly(peptide), and poly(dehydropyran). The bioerodable-mediated
dosage form comprises 2.0 mg to 750 mg of glipizide compounded with
the bioerodable polymer.
The diffusion-mediated dosage form 10 comprises a
membrane-controlled diffusion that permits diffusion of glipizide
through a polymer membrane or diffusion of glipizide through a
porous polymer membrane. The diffusion mediated dosage form 10
structurally includes a polymer matrix with glipizide thereon that
is released by the process of diffusion, and a reservoir or depot
polymer dosage form with glipizide in the reservoir that is
released therefrom by a process of diffusion through a contacting
polymer rate-governing membrane. Representative of polymers for
providing a diffusional dosage form comprise a member selected from
the group consisting of poly(olefin), poly(vinyl),
poly(carbohydrate), poly(peptides), poly (condensation),
poly(rubber), and poly(silicon). Representative of specific
polymers are a member selected from the group consisting of
poly(ethylene), poly(propylene), copoly (ethylene-vinylacetate),
poly(isobutylethylene), poly (vinylacetate), cross-linked
poly(vinyl-alcohol), poly (methyacrylate), poly(amide),
poly(ester), poly(ether), and poly(silicone).
The ion-exchange mediated dosage form comprises
water-insoluble-crosslinked polymers with glipizide bound to the
resin. The glipizide is released at a rate controlled by the
glipizide-resin complex by the ionic environment within the
gastrointestinal tract. The ion-exchanged mediated dosage form
comprises cation-exchange resins containing electronegative charges
and anion-exchange resins containing electropositive charges. The
cation-exchange resins include strong-acid weak-acid resins as with
sulfonic acid, carboxylic acid, and phosphonic acid, and the
anion-exchange resins include strong-base and weak-base resins as
with quaternary ammonium, secondary amine, tertiary amine aromatic,
and tertiary amine aliphatic resins. Specific examples of
ion-exchange resins mention is made of acidic ion-exchange resins
mention is made of acidic ion-exchange resins such as Amberlite
IR-120, basic ion-exchange resins such Amberlite IRA-400, and weak
basic ion-exchange resins such as Amberlite IR-45.
PROCEDURES FOR MANUFACTURING THE DOSAGE FORM
Dosage form 10 of this invention is manufactured by standard
techniques. For example, in one manufacture the drug glipizide is
mixed with other composition-forming ingredients and the mix then
pressed into a solid lamina possessing dimensions that correspond
to the internal dimensions of the compartment space adjacent to the
passageway. In another embodiment the beneficial drug glipizide and
other composition forming ingredients and a solvent are mixed into
a solid, or into a semisolid, by conventional methods such as
ballmilling, calendering, stirring, or rollmilling, and then
pressed into a preselected lamina forming shape. Next, a lamina
composition comprising the osmopolymer and the osmagent are placed
in contact with the lamina comprising the beneficial drug
glipizide, and the two lamina comprising the laminate are
surrounded with a semipermeable wall. The lamination of the
glipizide composition and the osmopolymer displacement composition
can be accomplished by using a two-layer tablet press technique.
The wall can be applied by molding, spraying, or dipping the
pressed shapes into wall-forming formulations. Another preferred
technique that can be used for applying the wall is the air
suspension coating procedure. This procedure consists in suspending
and tumbling the two layered laminate in a current of air until the
wall forming composition surrounds the laminate. The air suspension
procedure is described in U.S. Pat. No. 2,799,241; in J. Pharm.
Assoc., Sci. Ed., Vol. 48 pp 451-59 (1959); and ibid, Vol. 49, pp
82-84, (1960). Other standard manufacturing procedures are
described in Modern Plastics Encyclopedia, Vol. 46, pp 62-70,
(1969); and in Pharmaceutical Sciences, by Remington, 14th Ed., pp
1626-1978, (1970), published by Mack Publishing Co., Easton,
Pa.
The bioerodable-mediated dosage form is provided by dispensing or
mixing the drug into the bioerodible polymer by blending by
spatula, in a v-shaped blender, or on a three-roll mill. The blend
is heated until pliable to thoroughly mix the polymer and drug to
yield the loaded polymer. After the blend cools to room
temperature, the blend can be molded into a preselected design and
shaped and sized for therapeutic use.
A diffusion-mediated dosage form is fabricated by mixing the drug
in particulate form with a polymer, which can be in solid,
semi-solid or liquid form, and distributed therethrough by
ballmilling, calendering, stirring, or shaking. Monomers or
prepolymers can be used to form the reservoir, or a matrix formed
in situ. A reservoir, or matrix comprising drug distributed
therethrough can be formed into a solid shape by molding, casting,
pressing, extruding or drawing. A polymeric membrane is applied to
a reservoir by wrapping, laminating or heat shrinking, or the
polymer membrane can be formed by drawing or stamping the polymer
thereto. A preformed shape of the polymer, such as tube can be
filled with drug and seal to form a closed diffusional form. A
polymer membrane, or matrix can be converted to a solid by curing
to yield the desired dosage form.
An ion-exchanged mediated dosage form where the absorption of the
drug onto the ion-exchange resin to form a drug resin complex, is
provided by mixing the drug with an aqueous suspension of the resin
and the complex is then dried. Absorption of the drug onto the
resin is detected by a change in the pH of the reaction medium. The
ion-exchange resin drug complex can be solvated by the use of
solvating agents such as polyethylene glycol to enable this complex
to release the drug at a controlled-rate over an extended period of
drug therapy.
Exemplary solvents suitable for manufacturing the wall, laminate,
compositions, comprise inert inorganic and organic solvents that do
not adversely affect the final wall and the final laminates. The
solvents broadly comprise a member selected from the group
consisting of aqueous solvents, alcohols, ketones, esters, ethers,
aliphatic hydrocarbons, halogenated solvents, cycloaliphatics,
aromatics, heterocyclic solvents, and mixtures thereof. Typical
solvents comprise acetone, diacetone, alcohol, methanol, ethanol,
isopropyl alcohol, butyl alcohol, methyl acetate, ethyl acetate,
isopropyl acetate, n-butyl acetate methyl isobutyl ketone,
methylpropyl ketone, n-hexane, n-heptane, ethylene glycol monethyl
ether, ethylene glycol monethyl acetate, methylene dichloride,
ethylene dichloride, propylene dichloride, acetone and water,
acetone and methanol, acetone and ethyl alcohol, methylene
dichloride and methanol, ethylene dichloride and methanol, and the
like.
DETAILED DISCLOSURE OF EXAMPLES OF THE INVENTION
The following examples are merely illustrative of the present
invention, and they should not be considered as limiting the scope
of this invention in any way, as these examples and other
equivalents thereof will become apparent to those versed in the art
in the light of the present disclosure, the drawings and the
accompanying claims.
EXAMPLE 1
An oral dosage form, adapted, designed and shaped as drug delivery
system for admittance into the gastrointestinal tract of a patient
in need of glipizide is manufactured as follows: first, 369 g of
pharmaceutically acceptable hydroxypropylcellulose comprising a
60,000 average molecular weight is passed through a 20 mesh screen,
followed by passing through a 40 mesh screen 162 g of
pharmaceutically acceptable polyvinylpyrrolidone comprising a
40,000 average molecular weight. Next, the two screened ingredients
are blended with 66 g of glipizide to form a homogeneous blend. The
blend is suspended in a fluidized bed and sprayed with an atomized
spray comprising an ethanol:water (70:30 vol:vol) solution until
granules are formed of the three ingredients. The freshly prepared
granules then are passed through a 20 mesh screen. Finally, the
screened granulation is mixed with 3 g of magnesium stearate in a
rollermill for 5 minutes.
Next, a separate hydrogel granulation is prepared as follows:
first, 389 g of pharmaceutically acceptable sodium
carboxymethylcellulose having 700,000 molecular weight, 174 g of
sodium chloride, 30 g of pharmaceutically acceptable
hydroxypropylmethylcellulose comprising a 11,200 molecular weight
and 6 g of ferric oxide separately are screened through a 40 mesh
screen. Then, all the screened ingredients are mixed to produce a
homogeneous blend. Next, 300 ml of denatured anhydrous ethanol is
added slowly to the blend with continuous mixing for about 5
minutes. The freshly prepared wet granulation is screened through a
20 mesh screen, allowed to dry at room temperature for 16 hours,
and again passed through a 20 mesh screen. The screened granulation
is mixed with 1.5 g of magnesium stearate in a rollermill for about
5 minutes.
Next, the glipizide granulation, and the hydrogel granulation are
compressed into a bilaminate tablet arrangement. First, 200 mg of
the glipizide composition is added to a 0.375 inch (9.5 mm) punch
and tamped, then, 140 mg of the hydrogel granulation is added to
the punch and the two laminae are pressed into a solid, contacting
arrangement.
Next, the bilaminate is coated with a semipermeable wall. The
semipermeable wall-forming composition comprises 93% cellulose
acetate having a 39.8% acetyl content, and 7% polyethylene glycol
having a 3350 molecular weight. The wall-forming composition is
dissolved in a cosolvent comprising acetone: water (90:10 wt:wt) to
make a 4% solids solution. The wall-forming composition is sprayed
onto and around the bilaminate in an Aeromatic.RTM. Air Suspension
Coater.
Then, a 25 mil (0.635 mm) exit orifice is mechanically drilled on
the glipizide side of the osmotic dosage form. The residual solvent
is removed by drying the osmotic system for 48 hours at 50.degree.
C. and 50% humidity. The osmotic systems are dried for 1 hour at
50.degree. C. to remove excess moisture. Attached drawing FIG. 4
shows the in vitro release rate profile for glipizide from the
finished osmotic system as released in distilled water. The error
bars represent the standard deviation added to and subtracted from
the mean of five osmotic delivery system. An osmotic dosage form
provided by the invention comprises 11 wt % glipizide, 61.50 wt %
hydroxypropyl- cellulose of 60,000 molecular weight, 27.0 wt %
polyvinylpyrrolidone of 40,000 molecular weight, 0.5% magnesium
stearate in the glipizide composition; 64.8 wt % sodium
carboxymethylcellulose of 700,000 molecular weight, 29 wt % sodium
chloride, 5 wt % hydroxypropylmethylcellulose of 11,200 molecular
weight and 1.0 wt % ferric oxide, 0.2% magnesium stearate in the
hydrogel composition; and, 93.0 wt % cellulose acetate having a
39.8% acetyl content, and 7.0 wt % polyethylene glycol having a
3350 molecular weight in the semipermeable wall formulation.
EXAMPLE 2
A dosage form adapted, designed and shaped as an osmotic delivery
system is manufactured as follows: first, a glipizide composition
is provided by blending together into a homogeneous blend 478 g of
pharmaceutically acceptable polyethylene oxide comprising a 200,000
molecular weight, 66 g of glipizide and 54 g of pharmaceutically
acceptable hydroxypropylmethylcellulose comprising a 11,200
molecular weight. Then, 425 ml of denatured anhydrous ethanol is
added slowly with continuous mixing over 5 minutes. The freshly
prepared wet granulation is screened through a 20 mesh screen
through a 20 mesh screen, dried at room temperature for 16 hours,
and again screened through a 20 mesh screen. Finally, the screened
granulation is mixed with 1.5 g of magnesium stearate in a
rollermill for 5 minutes.
Next, a hydrogel composition is prepared as follows: first, 412.5 g
of pharmaceutically acceptable polyethylene oxide comprising a
7,500,000 molecular weight, 150 g of sodium chloride and 6 g of
ferric oxide separately are screened through a 40 mesh screen.
Then, all the screened ingredients are mixed with 30 g of
hydroxypropylmethylcellulose comprising a 11,200 molecular weight
to produce a homogeneous blend. Next, 300 mg of denatured anhydrous
alcohol is added slowly to the blend with continuous mixing for 5
minutes. The freshly prepared wet granulation is passed through a
20 mesh screen, allowed to dry at room temperature for 16 hours,
and again passed through a 20 mesh screen. The screened granulation
is mixed with 1.5 g of magnesium stearate in a rollermill for 5
minutes.
Next, the glipizide composition and the hydrogel composition are
compressed into bilaminate tablets. First, 200 mg of the glipizide
is added to a 0.375 inch (9.5 mm) punch and tamped, then, 140 mg of
the hydrogel composition is added and the laminae are pressed under
a pressure head of 2 tons into a contacting laminated
arrangement.
Then, the bilaminate arrangements are coated with a semipermeable
wall. The wall forming composition comprises 93% cellulose acetate
having a 39.8% acetyl content, and 7% polyethylene glycol having a
molecular weight of 3350. The wall-forming composition is dissolved
in an acetone:water (90:10 wt:wt) cosolvent to make a 4% solids
solution. The wall forming composition is sprayed onto and around
the bilaminate in an Aeromatic.RTM. Air Suspension Coater.
Next, a 25 mil (0.635 mm) exit passageway is mechanically drilled
through the semipermeable wall to connect the glipizide drug lamina
with the exterior of the dosage system. The residual solvent is
removed by drying for 48 hours at 50.degree. C. and 50% humidity.
Next, the osmotic systems are dried for 1 hour at 50.degree. C. to
remove excess moisture. The dosage form produced by this
manufacture provides a glipizide composition comprising 11 wt %
glipizide, 79.7 wt % polyethylene oxide of 200,000 molecular
weight, 9 wt % hydroxypropylmethylcellulose of 11,200 molecular
weight, and 0.3 wt % magnesium stearate; a hydrogel composition
comprising 68.8 wt % polyethylene oxide comprising a 7,500,000
molecular weight, 25 wt % sodium chloride, 5 wt %
hydroxypropylmethylcellulose, 1.0 wt % ferric oxide and 0.2 wt %
magnesium stearate; and a semipermeable wall comprising 93 wt %
cellulose acetate comprising a 39.8% acetyl content, and 7.0 wt %
polyethylene glycol comprising a 3350 molecular weight.
Accompanying drawing FIG. 5 depicts the in vitro release rate
profile of glipizide released from the final dosage form for four
dosage forms. The error bars represent the standard deviation added
to and subtracted from the mean of the dosage form.
EXAMPLE 3
A therapeutic dosage form for administering glipizide is made as
follows: first, 125 mg of glipizide is sieved through a No. 40 mesh
sieve and dry mixed with 125 mg of sorbitol, 100 mg of
hydroxypropylmethylcellulose, 25 mg of cellulose and 5 mg of sodium
chloride. Then, the mixture is blended with ethanol into a uniform,
doughy mass. The resulting dough is passed through a No. 20 mesh
sieve to form damp granules. The granules are air dried overnight,
then re-passed through a No. 20 mesh sieve. Next, the sieve
composition is compressed into a 15 mm oval tablet tooling at 2
tons pressure. The resulting compressed cores comprising the
homogenous glipizide formulation is coated with about 50 mg of a
50/50 wt % mixture of cellulose acetate and polyethylene glycol
deposited from a 95/5 wt % acetone and water solution. Then, the
coated dosage form is air dried overnight, and an exit port drilled
through the semipermeable wall connecting the exterior of the
dosage form with the glipizide.
EXAMPLE 4
A diffusion-mediated dosage form is prepared as follows: first 75
mg of glipizide is mixed with 50 parts of poly (dimethylsiloxane)
and 1 part of silicone oil, and to this well-stirred mixture is
added 0.15 parts by weight of stannous actoate curing catalyst, and
the mixture injected into a poly(ethylene) tube and cured for 30
minutes. Then, the cured reservoir is removed from the
poly(ethylene) tube and placed inside a rate-controlling
copoly(ethylene-vinyl acetate) tube and sealed with
poly(tetrafluoroethylene) plugs and cyanoacrylate adhesive. The
dosage form releases glipizide over 24 hours.
EXAMPLE 5
A bioerodible delivery system is prepared by heating
poly(2.2-dioxotrans-1, 4-cyclohexane dimethylene tetrahydrofuran)
to 120.degree. C. and blending therein glipizide and dispersed with
mixing for 5 minutes into the hot melt of the polymer. After
cooling to room temperature, the glipizide-bioerodable polymer
formulation is pressed into a film under 10,000 psi for 5 minutes
and placed inside a capsule, and on oral administration the dosage
form releases glipizide at a rate controlled over time.
DISCLOSURE OF A METHOD OF USING THE INVENTION
The invention pertains further to a method for delivering the
beneficial drug glipizide orally at a controlled rate to a warm
blooded animal in need of glipizide therapy by a method selected
from the group consisting of osmotic, diffusion, bioerosion and
ion-exchange. One method provided by the invention comprises the
steps of: (A) admitting into the warm-blooded animal a dosage form
comprising: (1) a wall surrounding a compartment, the wall
comprising at least in part a semipermeable polymeric composition
permeable to the passage of fluid and substantially impermeable to
the passage of glipizide; (2) a pharmaceutically acceptable
composition in the compartment comprising about 2.0 ng to 750 mg of
hypoglycemic glipizide for performing an antidiabetic program; (3)
a hydrogel composition in the compartment comprising a
poly(ethylene) oxide having a 4,000 to 7,500,000 molecular weight
for imbibing and absorbing fluid for pushing the glipizide
composition from the dosage form; and, (4) at least one passageway
in the wall for releasing glipizide; (B) imbibing fluid through the
semipermeable wall at a rate determined by the permeability of the
semipermeable wall and the osmotic pressure gradient across the
semipermeable wall causing the hydrogel composition to expand and
swell; and (C) delivering the beneficial glipizide from the dosage
form through the exit passage to the warm blooded animal over a
prolonged period of time to produce the desired hypoglycemic
effect.
Another dosage form administered according to the method of the
invention comprises the steps of: (A) admitting into a patient in
need of glipizide therapy a dosage form comprising: (1) a wall
surrounding a compartment, the wall comprising a semipermeable
composition permeable to the passage of fluid and substantially
impermeable to the passage of glipizide; (2) a glipizide
pharmaceutically acceptable composition in the compartment
comprising 2.0 ng to 750 mg of hypoglycemic glipizide for
performing an antidiabetic program; an expandable, push composition
in the compartment comprising a carboxymethylcellulose having a
200,000 to 1,000,000 molecular weight for imbibing and absorbing
fluid for pushing the glipizide composition from the dosage form;
and, (4) at least one passageway in the semipermeable causing the
expandable composition to expand and push the glipizide composition
from the dosage form; and (C) delivering the glipizide at a rate of
10 ng to 25 mg per hour over a period of 2 to 24 hours from the
dosage form through the exit port to produce the desired
hypoglycemic effect.
The glipizide can be administered by administering a dosage form
comprising a semipermeable wall that surrounds a compartment
housing a composition comprising glipizide and an osmotic effective
solute that imbibes fluid through the semipermeable wall into the
compartment thereby causing the glipizide to be pumped through the
exit port at a rate controlled by the dosage form at 10 ng to 25 mg
per hour over an extended period up to 24 hours.
The method comprises further administering glipizide from a dosage
form comprising a diffusion-releasing polymer that release
glipizide from a polymer glipizide matrix or through a polymer from
a glipizide reservoir at a diffusion controlled-rate of
administration over an extended time. The method comprises also
administering glipizide at a bioerodable controlled rate and at an
ion-exchange controlled-rate over an extended period of time.
In summary, it will be appreciated that the present invention
contributes to the art an unexpected and unforseen dosage form that
possesses the practical utility for administering aqueous insoluble
glipizide from a dosage form at a dose metered release rate per
unit time. While the invention has been described and pointed out
in detail with reference to operative embodiments thereof it will
be understood that those skilled in the art that various changes,
modifications, substitutions and omissions can be made without
departing from the spirit of the invention. It is intended,
therefore, that the invention embrace those equivalents within the
scope of the claims which follow.
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