(12) United States Patent
`Gullapalli
`
`111111
`
`1111111111111111111111111111111111111111111111111111111111111
`US006251426Bl
`US 6,251,426 Bl
`Jun.26,2001
`
`(10) Patent No.:
`(45) Date of Patent:
`
`(54)
`
`IBUPROFEN-CONTAINING SOFTGELS
`
`(75)
`
`Inventor: Rampurna Prasad Gullapalli,
`Greensboro, NC (US)
`
`(73) Assignee: Banner Pharmacaps, Inc., High Point,
`NC (US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`(21) Appl. No.: 09/389,003
`
`(22) Filed:
`
`Sep. 2, 1999
`
`(51)
`
`Int. Cl? ............................... A61K 9/48; A61K 9/66;
`A61K 9/64; A61K 9/58
`(52) U.S. Cl. .......................... 424/451; 424/452; 424/455;
`424/456; 424/462; 514/772.5
`(58) Field of Search ..................................... 424/455, 456,
`424/451, 452; 514/570, 629, 960, 772.8
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`4,690,823 * 9/1987 Lohner et a!. ....................... 424/456
`4,744,988 * 12/1991 Brox ..................................... 424/456
`4,780,316 * 10/1988 Brox ..................................... 424/456
`5,006,595
`4/1991 Smith et a!.
`......................... 524/548
`5,071,643 * 12/1991 Yu eta!. .............................. 514/570
`5,141,961 * 8/1992 Coapman ............................. 514/629
`
`5,360,615
`5,376,688
`5,431,916
`5,468,502
`5,484,606
`5,510,385
`5,538,737
`5,641,512
`5,660,859
`5,827,852
`
`11/1994 Yu et a!.
`.............................. 424/455
`12/1994 Morton eta!. ....................... 514/786
`7/1995 White ................................... 424/451
`11/1995 Argiriadi et a!. .................... 424/456
`1!1996 Dhabhar ............................... 424/455
`4/1996 Stroppolo eta!. ................... 514/555
`7/1996 Leonard eta!. ..................... 424/451
`6/1997 Cimiluca .............................. 424/455
`8/1997 Cody et a!. .......................... 424/451
`10/1998 Russell et a!. . ... .... ... ... ... ... ... 514/255
`
`FOREIGN PATENT DOCUMENTS
`wo 95/19759
`7/1995 (WO) ............................ A61K/47/10
`wo 00/30619
`6/2000 (WO) .............................. A61K/9/48
`* cited by examiner
`
`Primary Examiner-Thurman K. Page
`Assistant Examiner----1sis Ghali
`(74) Attorney, Agent, or Firm-Rhodes & Mason, P.L.L.C.
`
`(57)
`
`ABSTRACT
`
`Liquid softgel fill formulations containing ibuprofen in free
`acid form, and softgel capsules comprised of a gelatin sheath
`enclosing such fill formulations, are prepared by dissolving
`more than 30% of ibuprofen in free acid form in polyeth(cid:173)
`ylene glycol and at least 10% by weight of a polyvinylpyr(cid:173)
`rolidone having an average molecular weight of from about
`2,000 to about 54,000. The formulations may also include a
`surfactant to increase the bioavailability of the ibuprofen.
`
`26 Claims, No Drawings
`
`Petitioner - Catalent Pharma Solutions
`Ex. 1020, Pg. 1 of 5
`
`

`

`US 6,251,426 Bl
`
`1
`IBUPROFEN-CONTAINING SOFTGELS
`
`BACKGROUND OF THE INVENTION
`
`s
`
`2
`fen in free acid form in solution; from about 30 to about 60%
`by weight polyethylene glycol; and from about 10 to about
`30% by weight of polyvinylpyrrolidone.
`More specifically, liquid softgel fill formulations contain-
`ing ibuprofen in free acid form, and softgel capsules com(cid:173)
`prised of a gelatin sheath enclosing such fill formulations,
`are prepared by dissolving more than 30% of ibuprofen in
`free acid form in polyethylene glycol and at least 10% by
`weight of a polyvinylpyrrolidone having an average molecu-
`10 lar weight of from about 2,000 to about 54,000. The for(cid:173)
`mulations may also include a surfactant to increase the
`bioavailability of the ibuprofen.
`
`DETAILED DESCRIPTION OF THE
`INVENTION
`
`(1) Field of the Invention
`The present invention relates generally to softgels or soft
`gelatin capsules and fill compositions therefor, and in par(cid:173)
`ticular to a soft gelatin capsule that contains a highly
`concentrated solution of ibuprofen in its free form.
`(2) Description of the Prior Art
`U.S. Pat. No. 4,690,823 to Lohner et al. describes a
`process for manufacturing ibuprofen-containing soft gelatin
`capsules in which up to 30 parts by weight of ibuprofen in
`free form is dissolved in from 70 to 85 parts by weight of
`polyoxyethylene-polyoxypropylene polymer or in a mixture 15
`of from 30 to 76 parts by weight of a polyalkylene glycol and
`from 7 to 40 parts by weight of a surfactant having a very
`rapid and high bio-availability of the active ingredient.
`Preferred suitable surfactants include, for example, poly(cid:173)
`oxyethyleneglycerol trihydroxystearate, polyoxyethylene 20
`(C12- 18)-fatty alcohol ethers, polyoxyethylene stearate,
`polyoxyethylenesorbitan mono(C12- 18)-fatty acid esters,
`and polyoxyethylene-polyoxypropylene polymer.
`In the Lohner et al. process, up to 30 parts by weight of
`free form ibuprofen is dissolved by heating the free form 25
`ibuprofen with the selected solvent at a temperature of 45°
`to 60° C. If a concentration of ibuprofen greater than the
`maximum 30 parts by weight possible in solution is desired,
`up to 40 parts additional parts by weight of ibuprofen may
`also be suspended in the fill.
`Softgel fills containing high concentrations of ibuprofen
`as a mixture of ibuprofen in free form and its salts are
`described in U.S. Pat. Nos. 5,071,643 and 5,360,615 to Yu
`et al. These fill formulations may be liquid, semi-solid or
`solid, and are formed by mixing 40-80% by weight
`ibuprofen, 0.1-1.5 moles of hydroxide ion per mole of
`ibuprofen, 1-20% by weight water, and 4-12% by weight
`glycerine or propylene glycol in polyethylene glycol. Solu(cid:173)
`bility of the ibuprofen salts is further enhanced 2-10% by
`the further addition of 3-10% by weight of glycerin, or
`propylene glycol or 1-20% by weight of polyvinylpyrroli(cid:173)
`done.
`The preferred average molecular weight of the polyvi(cid:173)
`nylpyrrolidone is 10,000-100,000. Higher percentages of
`above 5% polyvinylpyrrolidone, and higher molecular
`weight polyvinylpyrrolidone are used to prepare semi-solid
`and solid formulations for suppositiories, two piece
`capsules, and tablets.
`Upon mixing under the conditions described by Yu et al.,
`the polyethylene glycol acts to dissolve the free form of the
`ibuprofen; the hydroxyl ions source, e.g., sodium hydroxide
`or potassium hydroxide, partially forms an ibuprofen salt,
`and the water forms a solvation sphere around the acid salt
`permitting it to go into solution in the polyethylene glycol.
`While softgel fill compositions containing ibuprofen salts
`can be produced by the above procedures, there is still a need
`for liquid softgel fill formulations with high concentrations,
`i.e., greater than 30% by weight, of ibuprofen in solution in
`its free acid form. In particular, there is a need for highly
`concentrated solutions containing ibuprofen in its free form
`that do not adversely affect the softgel capsules over an
`extended period of time.
`
`SUMMARY OF THE INVENTION
`The present invention relates to a liquid softgel fill
`formulation comprising greater than 30% by weight ibupro-
`
`65
`
`30
`
`35
`
`40
`
`The present invention relates to softgel fill formulations
`containing high concentrations, i.e., greater than 30% by
`weight of ibuprofen in its free acid form, and in particular to
`highly concentrated, preferably non-aqueous, ibuprofen fill
`formulations. Such formulations, when encapsulated into
`soft gelatin one-piece capsule sheaths by known techniques,
`provide long term stability, while still being of an acceptable
`size to the consumer. When used in the following
`description, "ibuprofen" will be understood to mean ibupro(cid:173)
`fen in its free acid form.
`It has been found that these formulations can be prepared
`by dissolving ibuprofen in a solvent comprised of polyeth(cid:173)
`ylene glycol and polyvinylpyrrolidone, with each of the
`solvent components being present in a defined amount in the
`composition, and with each component having defined char(cid:173)
`acteristics. Preferably, the formulation also includes a sur-
`factant to enhance bioavailability of the ibuprofen.
`Specifically, the formulations of the present invention are
`comprised of greater than 30% and up to 40% or more by
`weight ibuprofen, from 30 to 60% by weight polyethylene
`glycol, and from 10 to 30% by weight of polyvinylpyrroli(cid:173)
`done. Preferably, the formulations are comprised of from 35
`to 40% by weight ibuprofen, from 30 to 50% by weight
`polyethylene glycol, and from 15 to 30% by weight of
`polyvinylpyrrolidone.
`It will be understood that the percentages of the above
`ingredients in a given formulation, which may also have
`other ingredients present, will be adjusted to total100%. For
`45 example, up to 6% of a nasal decongestant, such as pseu(cid:173)
`doephedrine hydrochloride, or up to 10% of an
`antihistaminic, such as diphenhydramine hydrochloride,
`may be included in the formulation.
`The preferred embodiments of the invention also contain
`so at least about 10%, preferably from about 1% to about 10%
`by weight of a surfactant. Preferably, the surfactants are
`characterized by the capability to enhance the bioavailability
`of the ibuprofen, while being miscible with polyethylene
`glycol to form a clear solution. Suitable surfactants include
`ss esters of d-alpha tocopheryl, polyoxyethylene castor oil
`derivatives, and polyglycolyzed glycerides. Polyoxyethyl(cid:173)
`ene castor oil derivatives are the reaction products of eth(cid:173)
`ylene oxide and castor oil or hydrogenated castor oil sold,
`for example, as Cremophors by BASF. Suitable polyglyco-
`60 lyzed glycerides are sold under the trademark Gelucire by
`Etablissements Gattefosse. An especially preferred surfac(cid:173)
`tant is d-alpha tocopheryl polyethylene glycol 1000 succi(cid:173)
`nate sold by Eastman Chemical Company under the trade(cid:173)
`mark Vitamin E TPGS.
`The polyethylene glycol component of the formulation
`should have an average molecular weight of up to about
`1,000 in order to provide a liquid fill formulation. Preferably,
`
`Petitioner - Catalent Pharma Solutions
`Ex. 1020, Pg. 2 of 5
`
`

`

`US 6,251,426 Bl
`
`4
`gelatins or a mixture thereof. Limed bone, acid bone, fish
`and/or pig skin gelatins may be used.
`
`5
`
`The sheath plasticizer preferably is sorbitol, sorbitol spe(cid:173)
`cial (a mixture of sorbitol and sorbitan), maltitol, or a
`mixture thereof While glycerin can be used as a plasticizer,
`it has been found that the ibuprofen may esterify with the
`glycerin, reducing the amount of available free form ibu(cid:173)
`profen. Therefore, the non-glycerin plasticizers are pre(cid:173)
`ferred.
`The sheath formulations may also contain other
`ingredients, such as taste modifiers, coloring agents, and
`moisture retaining agents. Taste modifiers include non(cid:173)
`reducing sugars, such as xylitol, maltitol, or Lycasin®
`manufactured by Raquette America, Inc. of Keokuk, Iowa
`and normally will comprise up to about 5% by weight of the
`sheath composition. Suitable moisture retaining agents
`include celluloses, cellulose derivatives, starches, starch
`derivatives, vegetable gums, non-hygroscopic, mono-, di-
`20 and oligosaccharides, and silicon dioxide. Various FD&C
`coloring agents may be used to impart the desired color to
`the capsule.
`In order to be acceptable to the consumer, the softgel
`capsule should be of a size that is easily swallowed.
`25 Generally, the fill size of the capsule will be less than 600
`mg, and preferably about 500 mg or less, for the capsule to
`be of an acceptably small dimension. The required effective
`dosage of ibuprofen will normally be at least 175 mg, and
`preferably about 200 mg. Therefore, the preferred capsules
`will contain at least about 35% by weight of ibuprofen. The
`overall volume of the fill is also made possible by the fact
`that only polyethylene glycol and polyvinylpyrrolidone are
`required for dissolution, with a surfactant preferably being
`included to enhance bioavailability of the ibuprofen when
`35 ingested. Thus, the compositions may be free of water and
`other ingredients that increase the fill volume.
`The following examples are for the purpose of illustrating
`the present fill formulation, and softgels comprised of these
`fill formulation, and are not to be taken as in any way
`limiting the scope of the invention. Examples 1-10 are
`representative fill formulations containing in excess of 30%
`by wt. ibuprofen in its free acid form. Examples 11-13 are
`representative sheath formulations used to encapsulate the
`fill formulations of Examples 1-10.
`
`45
`
`3
`the polyethylene glycol has an average molecular weight of
`at least about 200, with an average molecular weight of from
`about 400 to about 1,000 being preferred. PEG 600 is
`especially preferred.
`The average molecular weight of the polyvinylpyrroli-
`done used in the present formulations may be in the range of
`from 2,000 to 54,000, but preferably is in the range of from
`about 2,000 to about 10,000. Preferred polyvinylpyrroli(cid:173)
`dones are sold under the trademarks Kollidon 12 PF and
`Kollidon 17 PF by BASF. These lower molecular weight 10
`polyvinylpyrrolidones have approximate molecular weights
`of 2,500 and 10,000 respectively. Another suitable polyvi(cid:173)
`nylpyrrolidone is sold under the trademark Plasdone C-15
`by ISP, and has a molecular weight of about 8,000. Unlike
`Yu, the present invention employs larger amounts of lower 15
`molecular weight polyvinylpyrrolidones to ensure that a
`liquid fill is obtained.
`An additional advantage of these higher amounts of
`polyvinylpyrrolidone is the apparent reduction in the esteri(cid:173)
`fication reaction between the ibuprofen and the polyethylene
`glycol, a known disadvantage of mixing these two ingredi(cid:173)
`ents that results in the reduction of available ibuprofen in its
`free acid form. Use of the higher percentages of polyvi(cid:173)
`nylpyrrolidone permits a corresponding reduction in the
`amount of polyethylene glycol required.
`The fill formulations may be prepared by heating the
`polyethylene glycol and surfactant to 55±5° C., while mix(cid:173)
`ing. The ibuprofen and polyvinylpyrrolidone are added and
`dissolved during heating and mixing. The procedure is
`carried out under a nitrogen atmosphere, and the final 30
`formulation is deaerated.
`The fill formulation is encapsulated into one-piece gelatin
`sheath or shell that includes a plasticizer to control the
`softness and flexibility of the sheath, water, and optionally,
`other additives, such as flavorants, colorants, opacifiers, etc.
`The softgel capsules may be produced in a known manner
`with a rotary die process in which a molten mass of a gelatin
`sheath formulation is fed from a reservoir onto drums to
`form two spaced sheets or ribbons of gelatin in a semi- 40
`molten state. These ribbons are fed around rollers and
`brought together at a convergent angle into the nip of a pair
`of roller dies that include opposed die cavities. A fill
`formulation to be encapsulated is fed into the wedge-shaped
`joinder of the ribbons.
`The gelatin ribbons are continuously conveyed between
`the dies, with portions of the fill formulation being trapped
`between the sheets inside the die cavities. The sheets are
`then pressed together, and severed around each die so that
`opposed edges of the sheets flow together to form a con- 50
`tinuous gelatin sheath around the entrapped medicament.
`The part of the gelatin sheet that is severed from the
`segments forming the capsules is then collected for
`recycling, and the soft capsules are dried.
`Various sheath formulations known in the prior art may be 55
`used to encapsulate the fill formulations of the present
`invention. For example, suitable sheath formulations may
`include from about 35 to about 50% by weight gelatin; at
`least 20% by weight, and preferably up to about 40% by
`weight, of a plasticizer; and from about 25 to about 50% by 60
`weight water. These formulations, when formed into cap(cid:173)
`sules and dried, will result in capsule sheaths comprised of
`from about 45 to about 75% by weight gelatin; from about
`20% to about 40% by weight plasticizer; and from about 5
`to about 15% by weight water.
`The gelatin will normally have a bloom in the range of
`from about 150 to about 275, and may be Type A or B
`
`Example 1
`
`Fill Ingredients
`
`Ibuprofen
`PEG 600
`Kollidon 17 PF
`Vitamin E TPGS
`
`Example 2
`
`Fill Ingredients
`
`Ibuprofen
`PEG 600
`Kollidon 17 PF
`Vitamin E TPGS
`Water, purified
`
`%bywt.
`
`35
`37
`22
`
`%bywt.
`
`35
`35
`20
`5
`5
`
`65
`
`Petitioner - Catalent Pharma Solutions
`Ex. 1020, Pg. 3 of 5
`
`

`

`US 6,251,426 Bl
`
`5
`
`Example 3
`
`Fill Ingredients
`
`%bywt.
`
`Ibuprofen
`PEG 600
`Kollidon 17
`Vitamin E TPGS
`
`37
`37
`20
`
`Example 4
`
`Fill Ingredients
`
`%bywt.
`
`Ibuprofen
`PEG 600
`Kollidon 30
`Cremophor RH 40
`Propylene glycol
`
`35
`40
`15
`5
`5
`
`Example 5
`
`Fill Ingredients
`
`Ibuprofen
`PEG 600
`Kollidon 17 PF
`Gelucire 44/14
`
`%bywt.
`
`35
`33
`22
`10
`
`Example 6
`
`Fill Ingredients
`
`%bywt.
`
`Ibuprofen
`PEG 600
`Kollidon 30
`Cremophor RH 60
`Propylene glycol
`
`35
`40
`15
`5
`5
`
`Example 7
`
`Fill Ingredients
`
`%bywt.
`
`Ibuprofen
`PEG 600
`Kollidon 30
`Cremophor RH 60
`Propylene glycol
`
`35
`35
`15
`10
`5
`
`Example 8
`
`Fill Ingredients
`
`Ibuprofen
`PEG 600
`Kollidon 17 PF
`
`%bywt.
`
`40
`40
`20
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`6
`
`Example 9
`
`Fill Ingredients
`
`Ibuprofen
`PEG 600
`Kollidon 17 PF
`Vitamin E TPGS
`
`%bywt.
`
`40
`40
`15
`5
`
`Example 10
`
`Fill Ingredients
`
`%bywt.
`
`Ibuprofen
`PEG 600
`Kollidon 17 PF
`Vitamin E TPGS
`
`40
`30
`25
`5
`
`Example 11
`
`Sheath Ingredients
`
`%bywt.
`
`Gelatin, lime bone
`Sorbitol, special
`Maltitol, 75%
`Water, purified
`
`42
`9
`12
`37
`
`Example 12
`
`Sheath Ingredients
`
`%bywt.
`
`Gelatin, lime bone
`Sorbitol, special
`Maltitol, 75%
`Water, purified
`
`42
`15
`
`37
`
`Example 13
`
`Sheath Ingredients
`
`%bywt.
`
`Gelatin, lime bone
`Glycerin
`Maltitol, 75%
`Water, purified
`
`42
`8
`12
`38
`
`Certain modifications and improvements will occur to
`those skilled in the art upon a reading of the foregoing
`description. It should be understood that all such modifica-
`tions and improvements have been deleted herein for the
`sake of conciseness and readability but are properly within
`the scope of the follow claims.
`What is claimed is:
`1. A liquid softgel fill formulation consisting essentially
`of:
`a) greater than 30% by weight ibuprofen in free acid form
`in solution;
`b) from about 30 to about 60% by weight polyethylene
`glycol;
`c) from about 10 to about 30% by weight of polyvinylpyr-
`rolidone; and
`d) from about 1 to about 10% by weight of a surfactant.
`
`Petitioner - Catalent Pharma Solutions
`Ex. 1020, Pg. 4 of 5
`
`

`

`US 6,251,426 Bl
`
`7
`2. The softgel fill formulation of claim 1, wherein said
`ibuprofen is present in an amount of at least about 35% by
`weight.
`3. The softgel formulation of claim 1, wherein said
`polyethylene glycol has an average molecular weight of
`from about 200 to about 1,000.
`4. The softgel formulation of claim 1, wherein said
`polyvinylpyrrolidone has an average molecular weight of
`from about 2,000 to about 54,000.
`5. The softgel fill formulation of claim 1, further including 10
`up to about 6% of a nasal decongestant or up to about 10%
`of an antihistaminic.
`6. The softgel fill formulation of claim 1, further including
`up to about 10% by weight of a surfactant to increase the 15
`bioavailability of said ibuprofen.
`7. The softgel formulation of claim 1, wherein said
`surfactant is selected from the group consisting of esters of
`d-alpha-tocopheryl, polyoxyethylene castor oil derivatives,
`and polyglycolyzed glycerides.
`8. A liquid softgel fill formulation consisting essentially
`of:
`a) greater than 30% by weight ibuprofen in free acid form
`in solution;
`b) from about 30 to about 60% by weight of polyethylene
`glycol having an average molecular weight of from
`about 200 to about 1,000;
`c) from about 10 to about 30% by weight of polyvinylpyr(cid:173)
`rolidone having an average molecular weight of from 30
`about 2,000 to about 54,000; and
`d) from about 1 to about 10% by weight of a surfactant to
`increase the bioavailability of said ibuprofen.
`9. The softgel fill formulation of claim 8, wherein said
`polyethylene glycol is has an average molecular weight of 35
`about 600.
`10. The softgel formulation of claim 8, wherein said
`surfactant is selected from esters of d-alpha tocopheryl,
`polyoxyethylene castor oil derivatives, and polyglycolyzed
`glycerides.
`11. A softgel capsule comprised of a sheath enclosing a
`liquid fill, said fill consisting essentially of:
`a) greater than 30% by weight ibuprofen in free acid form
`in solution;
`b) from about 30 to about 60% by weight polyethylene 45
`glycol;
`c) from about 10 to about 30% by weight polyvinylpyr(cid:173)
`rolidone; and
`d) from about 1 to about 10% by weight of a surfactant. 50
`12. The softgel capsule of claim 11, wherein said ibupro(cid:173)
`fen is present in an amount of from about 35% to about 40%
`by weight of said fill.
`13. The softgel capsule of claim 11, wherein said poly(cid:173)
`ethylene glycol has an average molecular weight of from 55
`about 200 to about 1,000.
`14. The softgel capsule of claim 11, wherein said surfac(cid:173)
`tant is selected from esters of d-alpha tocopheryl, polyoxy(cid:173)
`ethylene castor oil derivatives, and polyglycolyzed glycer-
`~
`15. The softgel capsule of claim 11, wherein said poly(cid:173)
`vinylpyrrolidone has an average molecular weight of from
`about 2,000 to about 11,000.
`16. The softgel capsule of claim 11, wherein said sheath
`is comprised of from about 45 to about 75% by weight
`
`8
`gelatin, from about 20 to about 40% by weight of a
`plasticizer, and from about 5 to about 15% by weight water.
`17. The soft gel capsule of claim 11, further including up
`to about 6% of a nasal decongestant or up to about 10% of
`5 an antihistaminic.
`18. A softgel capsule comprised of a sheath enclosing a
`liquid fill, said fill consisting essentially of:
`a) at least 35% by weight ibuprofen in free acid form in
`solution;
`b) from about 30 to about 50% by weight polyethylene
`glycol having an average molecular weight of from
`about 200 to about 1,000;
`c) from about 15 to about 30% by weight of polyvinylpyr(cid:173)
`rolidone having an average molecular weight of from
`about 2,000 to about 11,000; and
`d) a surfactant to increase the bioavailability of said
`ibuprofen.
`19. The softgel capsule of claim 18, wherein said surfac-
`20 tant is selected from esters of d-alpha tocopheryl, polyoxy(cid:173)
`ethylene castor oil derivatives, and polyglycolyzed glycer(cid:173)
`ides.
`20. The softgel capsule of claim 18, wherein said sheath
`is comprised of from about 45 to about 75% by weight
`25 gelatin, from about 20 to about 40% by weight plasticizer,
`and from about 5 to about 15% by weight water.
`21. The capsule of claim 20, wherein said sheath plasti(cid:173)
`cizer is selected from the group consisting of sorbitol,
`sorbitol special, maltitol, and mixtures thereof.
`22. The capsule of claim 18, wherein the total weight of
`said capsule fill is less than 600 mg., and the weight of said
`ibuprofen is at least 200 mg.
`23. A liquid softgel fill formulation consisting essentially
`of:
`a) greater than 30% by weight ibuprofen in free acid form
`in solution;
`b) from about 30 to about 60% by weight polyethylene
`glycol;
`d) from about 10 to about 30% by weight of
`polyvinylpyrrolidone, wherein the ratio of polyethyl(cid:173)
`ene glycol to polyvinylpyrrolidone less than about
`2.5:1; and
`d) a surfactant to increase the bioavailability of said
`ibuprofen.
`24. The liquid softgel fill formulation of claim 23 wherein
`the ratio of polyethylene glycol to polyvinylpyrrolidone is
`between about 1.6:1 and about 1.8:1.
`25. A softgel capsule comprised of a sheath enclosing a
`liquid fill, said fill consisting essentially of:
`a) greater than 30% by weight ibuprofen in free acid form
`in solution;
`b) from about 30 to about 60% by weight polyethylene
`glycol;
`c) from about 10 to about 30% by weight
`polyvinylpyrrolidone, wherein the ratio of polyethyl(cid:173)
`ene glycol to polyvinylpyrrolidone is less than about
`2.5:1; and
`d) a surfactant to increase the bioavailability of said
`ibuprofen.
`26. The softgel capsule of claim 25 wherein the ratio of
`polyethylene glycol to polyvinylpyrrolidone is between
`about 1.6:1 and about 1.8:1.
`
`* * * * *
`
`40
`
`~
`
`Petitioner - Catalent Pharma Solutions
`Ex. 1020, Pg. 5 of 5
`
`