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`PROVISIONAL APPLICATION FOR PA TENT COVER SHEET
`-
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`This is a request for filing a PROVISIONAL APPLICATION FOR PATENT under 37 CFR 1.53{c).
`Bags.“
`-
`-
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`- =
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`
`
`Robert K.
`Richard C.
`Gary L.
`Joseph M.
`
`138-10 Franklin Ave.. Apt. 26, Flushing, NY 11355
`1287 Ballantrae Farm Drive, McLean. VA 22101
`903 Coltax Avenue, Kingsport, TN 3766!)
`5700 Cricket Place, McLean. VA 22101
`
`separately numbered sheets attached hereto
`E Additional inventors are being named on thr__
`TITLE OF THE INVENTION (230 characters max}
`THIN FILM WITH NON-SELF-AGGREGATING
`UNIFORM HETEROGENEITY AND DRUG DELIVERY
`
`Direct all correspondence to:
`CORRESPONDENCE ADDRESS
`
`g Customer Number I
`I —-—-
`
`
`Type Customer Number here
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`Firm or
`Individual Name
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`
`_
`08 2461“ __
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`$80.00
`
`Respectfully submitted,
`
`SIGNATURE
`
`g
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`_
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`Dam
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`1I30ID3
`
`REGISTRATION NC}.
`
`(If appropriate)
`Docket Number:
`
`43.523
`
`1199-4F’2
`
`"
`
`I
`
`I
`
`Jamie M. Larmann
`TYPED or PRINTED NAME
`
`TELEPHONE
`973-331—1700
`USE ONLY FOR FILING A PROVISIONAL APPLICATION FOR PA TENT
`This collection of information is required by 37 CFR 1.51. The information is used by the public to file (and by the PTO to process) a previsional
`application. Confidentiality is governed by 35 U.S.C. 122 and 3? CFR 1.14. This collection is estimated to take 8 hours to complete, including
`gathering, preparing‘ and submitting the complete provisional application to the PTO. Time will vary depending upon the individual case. Any
`comments on the amount of time you require to complete this form andlor suggestiOns for reducing this burden. should he sent to the Chief
`information Officer. US. Patent and Trademark Office. US. Department of Commerce, Washington. DC. 20231. DO NOT SEND FEES OR
`COMPLETED FORMS TO THIS ADDRESS. SEND TO: Box Provisional Application. Assistant Commissioner for Patents. Washington. DC.
`PlQSMALLIREVOb
`
`
`
`Mylan v. MonoSol
`Mylan V. MonoSol
`Page 1
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`IPR2017-00200
`IPR2017-00200
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`MonoSol Ex. 2011
`MonoSol Ex. 2011
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`METHOD OF PAYMENT OF FILING FEES FOR THIS PROVISIONAL APPLICATION FOR PATENT {check one)
`E Applicant claims small entity Status. See 3? CFR 1.27.
`FILING FEE
`E A check or money order is enclosed to cover the filing fees
`AMOUNTL
`W
`The Commissioner is hereby authorized to charge filing
`A
`fees or credit any overpayment to Deposit Account Numhe
`‘3
`Payment by credit card. Form PTO—2038 is attached.
`The invention was made by an agency of the United States Government or under a contract with an agenCy of the
`United States Government.
`fl No.
`D Yes, the name of the US. Government agency and the Government contract number are:
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`CE-RTIF‘ICA'IE OF MAILING BY "EXPRESS MAIL" (37 CFR 1.10)
`
`Applicant(s): Yang ct al.
`
`Serial No.
`
`Unassigned
`
`Fiting Date
`
`Ilercwith
`
`Examiner
`
`Unassigned
`
`THIN FILM \Vl'l‘H NON-9EI_,F-AGGREGATING
`Invention.
`' UNIFORM HE'I‘EROGENEITY AND DRUG DELIVERY
`
`Docket No.
`
`1199~4P2
`
`Group Art Unit
`
`Unassigned
`
`I hereby certify that the foilowing correspondence:
`
`rovisional Patent Application (Spec. 89 pages} 28 pages informal drawings and Cover Sheet
`.heck $80.00
`Postcard
`
`(1 page)
`
`
`
`is being deposited with the United States Postal Service "Express Mail Post Office to Addressee" service under
`
`37 CFR 1.10 in an envelope addressed to: The Assistant Commissioner for Patents, Washington, DC. 20231 on
`
`(Men-111'}! type ofcarn-spondence)
`
`Jartuary 30, 2003
`(Date)
`
`_4_
`
`_
`
`_
`_ Jam_i_c M. Larmann
`__
`__
`(I:ch or Primed Name afPersmr flfaifr'ng Correspondence)
`
`flW/
`(31" "Emu: C!ch or r effing Correspondence)
`
`1
`
`EV261770229US
`
`
`("Express Mai!" Naming Label Nun-roar}
`
`Note: Each paper must have its own certificate of mailing.
`
`
`POBNR EWZ
`
`Page 2
`Pa
`
`
`
`

`

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`° 1199-4P2
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`THIN FILM WITH NON—SELF-AGGREGATING
`UNIFORM HETEROGENEITY AND DRUG DELIVERY SYSTEMS
`MADE THEREFROM
`
`CROSS-REFERENCE TO RELATED APPLICATIONS
`
`This application is a continuation-impart of PCTI’USOZI3257S filed October 1 i, 2002,
`
`which claims priority to US. Application No. 10f07'4,2?2, filed February 14, 2002 which claims
`
`priority to US. Provisional Application No. 60f328,868, filed October 12, 2001 and US.
`
`Provisional Application No. 6023 86,937, filed June 7, 2002; PCTI'USO2X32594, filed October 11,
`
`2002, which claims priority to US. Provisional Application No. 60f414,276, filed September 27,
`
`2002, US. Application No. 10/074,272,
`
`tiied February 14, 2002, which claims priority to US
`
`Provisional Application No. 603328368, filed October 12, 2001 and US. Provisional
`
`Application No. 60/386,937, filed June 7, 2002; and PCTz’US02/32542, filed October 11, 2002,
`
`which claims priority to US. Provisional Application No. 60871340, filed April 1 1, 2002, US.
`
`Application No. 10X074,272, filed February 14, 2002, which claims priority to
`
`Provisional
`
`Application No. 60/328,868, filed October 12, 2001 and US. Provisional Application No.
`
`608 86,93 7, filed June 7, 2002.
`
`FIELD OF THE INVENTION
`
`The invention relates to rapidly dissolving films and methods oftheir preparation. The
`
`films may also contain an active ingredient that is evenly distributed throughout the film. The
`
`even or uniform distribution is achieved by controlling one or more parameters, and particularly
`
`the elimination of air pockets prior to and during film formation and the use of a drying process
`
`that reduces aggregation or conglomeration of the components in the film as it forms into a solid
`
`structure.
`
`BACKGROUND OF THE RELATED TECHNOLOGY
`
`Active ingredients, such as drugs or pharmaceuticals, may be prepared in a tablet form to
`
`allow for accurate and consistent dosing. However, this form of preparing and dispensing
`
`medications has many disadvantages including that a large proportion of adjuvants that must be
`
`added to obtain a size able to be handled, that a larger medication form requires additional
`
`
`
`Page 3
`Pa e3
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`storage space, and that dispensing includes counting the tablets which has a tendency for
`
`inaccuracy.
`
`In addition, many persons, estimated to be as much as 23% of the pOpulation, have
`
`difficulty swallowing tablets. While tablets may be broken into smaller pieces or even crushed
`
`as a means of overcoming swallowing difficulties, this is not a suitable solution for many tablet
`
`or pill forms. For example, crushing or destroying the tablet or pill form to facilitate ingestiori,
`
`alone or in admixture with food, may also destroy the controlled release properties.
`
`As an alternative to tablets and pills, films may be used to carry active ingredients such as
`
`drugs, pharmaceuticals, and the like. However, historically films and the process of making drug
`
`delivery systems therefrom have suffered from a number of unfavorable characteristics that have
`
`not allowed them to be used in practice.
`
`Films that incorporate a pharmaceutically active ingredient are disclosed in expired US.
`
`Patent No. 4,136,145 to Fuchs, et al. ("Fuchs"). These films may be formed into a sheet, dried
`
`and then cut into individual doses. The Fuchs disclosure alleges the fabrication ofa uniform
`
`film, which includes the combination of water-soluble polymers, surfactants, flavors, sweeteners,
`
`plasticizers and drugs. These allegedly flexible films are disclosed as being useful for oral,
`
`topical or enteral use. Examples of specific uses disclosed by Fuchs include application ofthe
`
`films to mucosa] membrane areas ofthe body, including the mouth, rectal, vaginal, nasal and ear
`
`areas.
`
`Examination of films made in accordance with the process disclosed in Fuchs, however,
`
`reveals that such films suffer from the aggregation or conglomeration of particles, i.e., self-
`
`aggrcgation, making them inherently non-uniform. This result can be attributed to Fuchs’
`
`process parameters, which although not disclosed likely include the use of relatively long drying
`
`times, thereby facilitating intermolecular attractive forces, convection forces, air flow and the
`
`like to form such agglomeration.
`
`The formation of agglomerates randomly distributes the film components and any active
`
`present as well. When large dosages are involved, a small change in the dimensions of the film
`
`would lead to a large difference in the amount of active per film. If such films were to include
`
`
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`Page 4
`Pa e4
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`

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`low dosages of active, it is possible that portions of the film may be substantially devoid of any
`
`active. Since sheets of film are usually cut into unit doses, certain doses may therefore be devoid
`
`of or contain an insufficient amount of active for the recommended treatment. Failure to achieve
`
`a high degree of accuracy with respect to the amount of active ingredient in the cut film can be
`
`harmful to the patient. For this reason, dosage forms formed by processes such as Fuchs, would
`
`not likely meet the stringent standards of governmental or regulatory agencies, such as the U.S.
`
`Federal Drug Administration (“FDA” , relating to the variation of active in dosage forms.
`
`Currently, as required by various world regulatory authorities, dosage forms may not vary more
`
`than 10% in the amount of active present. When applied to dosage units based on films, this
`
`virtually mandates that uniformity in the film be present.
`
`The problems of self—aggregation leading to non-uniformity ofa film were addressed in
`
`U.S. Patent No. 4,849,246 to Schmidt ("Schmidt"). Schmidt specifically pointed out that the
`
`methods disclosed by Fuchs did not provide a uniform film and recognized that that the creation
`
`ofa non-uniform film necessarily prevents accurate dosing, which as discussed above is
`
`especially important in the pharmaceutical area. Schmidt abandoned the idea that a mono—layer
`
`film, such as described by Fuchs, may provide an accurate dosage form and instead attempted to
`
`solve this problem by forming a multi-layered film. Moreover, his process is a multi-step
`
`process that adds expense and complexity and is not practical for commercial use.
`
`Other U.S. Patents directly addressed the problems of particle self-aggregation and non-
`
`unifonnity inherent in conventional lilm forming techniques. In one attempt to overcome non-
`
`unifonnity, U.S. Patent 5,629,003 to Horstmann et al. and U.S. Patent 5,948,430 to Zerbe et al.
`
`incorporated additional ingredients, i.e. gel formers and polyhydric alcohols respectively, to
`
`increase the viscosity ofthe film prior to drying in an effort to reduce aggregation of the
`
`compenents in the film. These methods have the disadvantage of requiring additional
`
`components, which translates to additional cost and manufacturing steps. Furthermore, both
`
`methods employ the use the conventional time—consuming drying methods such as a high-
`
`temperature air-bath using a drying oven, drying tunnel, vacuum drier, or other such drying
`
`equipment. The long length of drying time aids in promoting the aggregation ofthe active and
`
`other adjuvant, notwithstanding the use of viscosity modifiers. Such processes also run the risk
`
`
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`Page 5
`Pa e5
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`of exposing the active, i.e., a drug, or vitamin C, or other components to prolonged exposure to
`
`moisture and elevated temperatures, which may render it ineffective or even harmful.
`
`In addition to the concerns associated with degradation of an active during extended
`
`exposure to moisture, the conventional drying methods themselves are unable to provide uniform
`
`films. The length of heat exposure during conventional processing, often referred to as the “heat
`
`history”, and the manner in which such heat is applied, have a direct effect on the formation and
`
`morphology of the resultant film product. Uniformity is particularly difficult to achieve via
`
`conventional drying methods where a relatively thicker film, which is well-suited for the
`
`incorporation of a drug active, is desired. Thicker uniform films are more difficult to achieve
`
`because the surfaces of the film and the inner portions of the film do not experience the same
`
`external conditions simultaneously during drying. Thus, observation of relatively thick films
`
`made from such conventional processing shows a non-uniform structure caused by convection
`
`and intermolecular forces and requires greater than 10% moisture to remain flexible. The
`
`amount of free moisture can often interfere over time with the drug leading to potency issues and
`
`therefore inconsistency in the final product.
`
`Conventional drying methods generally include the use of forced hot air using a drying
`
`oven, drying tunnel, and the like. The difficulty in achieving a uniform film is directly related to
`
`the rheological properties and the process of water evaporation in the film-forming composition.
`
`When the surface of an aqueous polymer solution is contacted with a high temperature air
`
`current, such as a film-forming composition passing through a hot air oven, the surface water is
`
`immediately evaporated forming a polymer film or skin on the surface. This seals the remainder
`
`of the aqueous film-forming composition beneath the surface, forming a barrier through which
`
`the remaining water must force itself as it is evaporated in order to achieve a dried film. As the
`
`temperature outside the film continues to increase, water vapor pressure builds up under the
`
`surface ofthe film, stretching the surface of the film, and ultimately ripping the film surface open
`
`allowing the water vapor to escape. As soon as the water vapor has escaped, the polymer film
`
`surface reforms, and this process is repeated, until the film is completely dried. The result ofthe
`
`repeated destruction and reformation of the film surface is observed as a "ripple effect" which
`
`produces an uneven, and therefore non—uniform film. Frequently, depending on the polymer, 3
`
`
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`Page 6
`Pa e6
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`surface will seal so tightly that the remaining water is difficult to remove, leading to very long
`
`drying times, higher temperatures, and higher energy costs.
`
`Other factors, such as mixing techniques, also play a role in the manufacture of'a
`
`pharmaceutical film suitable for commercialization and regulatory approval. Air can be trapped
`
`in the composition during the mixing process or later during the film making process, which can
`
`leave voids in the film product as the moisture evaporates during the drying stage. The film
`
`frequently collapse around the voids resulting in an uneven film surface and therefore, non-
`
`uniformity ofthe final film product. Uniformity is still affected cven ifthe voids in the film
`
`caused by air bubbles do not collapse. This situation also provides a non-uniform film in that the
`
`spaces, which are not uniformly distributed, are occupying area that would otherwise be
`
`occupied by the film composition. None of the abovc~mentioned patents either addresses or
`
`proposes a solution to the problems caused by air that has been introduced to the film.
`
`Therefore, there is a need for methods and compositions for film products, which use a
`
`minimal number of materials or components, and which provide a substantially non-self-
`
`aggregating uniform heterogeneity throughout the area of the films. Desirably, such films are
`
`produced through a selection ofa polymer or combination of polymers that will provide a
`
`desired viscosity, a film-forming process such as reverse roll coating, and a controlled, and
`
`desirably rapid, drying process which serves to maintain the uniform distribution of non~self—
`
`aggregated components without the necessary addition of gel formers or polyhydrie alcohols and
`
`the like which appear to be required in the products and for the processes of prior patents, such
`
`as the aforementioned Horstmann and Zerbe patents. Desirably, the films will also incorporate
`
`compositions and methods of manufacture that substantially reduce ‘or eliminate air in the film,
`
`thereby promoting uniformity in the final film product.
`
`SUMMARY OF THE INVENTION
`
`In One aSpect ofthc present invention, there is provided a film and a method of forming
`
`same which can be divided into equally sized dosage units having substantially equal amounts of
`
`each compositional component present. This advantage is particularly useful because it permits
`
`large area films to be initially formed, and subsequently cut into individual dosage units without
`
`
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`Page 7
`Pa e7
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`concern for whether each unit is compositionally equal. For example, the films of the present
`
`invention have particular applicability as pharmaceutical dosage delivery systems because each
`
`dosage unit, e.g., each individual dosage film unit, will contain the proper amount of drug.
`
`Pharmaceutical film dosage forms to date have not been marketed largely due to the inability to
`
`achieve this result.
`
`In a further aspect of the present invention, there is provided a film product that is formed
`
`by combining a polymer and a polar solvent, forming the combination into a film, and drying the
`
`film in a controlled manner, desirably by initially only applying heat to the bottom side of the
`
`film, in order to maintain a non-self-aggregating uniform heterogeneity. Desirably, during the
`
`initial bottom drying stage, substantially no convection currents, i.e. hot air currents, are
`
`permitted to travel across the tops ofthe films. Once the visco—elastic properties ofthc film are
`
`such that the film components are “locked” in place and cannot move to cause non-uniformity,
`
`other methods of heating may then be employed. The polar solvent may be water, a polar
`
`organic solvent, or a combination thereof. An active ingredient may be added to the polymer and
`
`water combination prior to the drying step. Alternatively, or in additiori to controlling the drying
`
`the film, the polymer may be selected in order to provide a viscosity that maintains the non~self-
`
`aggregating uniform heterogeneity. Moreover, the composition desirably is mixed in a manner
`
`to minimize the incorporation ol'air into the mixture and is desirably deaerated, such as by
`
`conditioning at room temperature, vacuum treatment or the like, to allow trapped air to escape
`
`prior to the drying process. This serves to eliminate bubble and void formation in the final film
`
`product, thereby further improving uniformity. Reverse roll is one particularly useful coating
`
`technique may also he uscd to form the film.
`
`In another aspect of the invention, there is a process for preparing a film with a
`
`substantially uniform distribution of components. The process includes the steps of combining a
`
`polymer component and water to form a uniformly distributed matrix. This matrix is then
`
`formed into a film and fed onto the top side ofa substrate surface having top and bottom sides.
`
`Heat is applied to the bottom side ofthe substrate surface in order to dry the film. The matrix
`
`from which the film is formed may also include an active ingredient. Also, either alternatively,
`
`or in addition to the particular method used to dry the film, the polymer may be selected in order
`
`
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`Page 8
`Pa e8
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`to provide a viscosity that maintains the non-self-aggregating uniform heterogeneity. Reverse
`
`roll coating technique may also be used to form the film.
`
`A further aspect of the present invention is a method of orally administering an active
`
`including the steps of:
`
`(a)
`
`preparing a film by the steps of:
`
`(i)
`
`combining a polymer, an active component, and water to form a material
`
`with a non—self-aggregating uniform heterogeneity;
`
`(ii)
`
`forming the material into a film; and
`
`(iii)
`
`drying the film in a controlled manner to maintain the non~self—
`
`aggregating uni form heterogeneity; and
`
`(b)
`
`introducing the film to the oral cavity ofa mammal.
`
`An even further aspect ofthe present invention is method of introducing an active
`
`component to liquid including the steps of:
`
`(a)
`
`preparing a film by the steps of:
`
`(i)
`
`combining a polymer, an active component, and water to form a material
`
`with a non~self—aggregating uniform heterogeneity;
`
`(ii)
`
`forming the material into a film; and
`
`(iii)
`
`drying the film in a controlled manner to maintain the non-self-
`
`aggregating uniform heterogeneity; and
`
`(b)
`
`(e)
`
`placing the film into a liquid; and
`
`allowing the film to dissolve.
`
`A still further aspect ofthe present invention provides a dosage form for the
`
`administration of an active including:
`
`(a)
`
`a first layer including a film formed by the steps of:
`
`(i)
`
`combining a polymer, an active component, and water to form a
`
`material with a non-self-agg‘regating uniform heterogeneity;
`
`(ii)
`
`forming said material into a film; and
`
`
`
`Page 9
`Pa e9
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`drying said film in a controlled manner to maintain said non-self-
`
`aggregating uniform heterogeneity; and
`
`(b)
`
`a substantially non-water soluble second layer.
`
`Another aspect ofthe present invention provides a method of preparing a dosage form for
`
`the administration of an active including the steps of:
`
`(a)
`
`combining a polymer, an active component, and water to form a material
`
`(b)
`
`(0)
`
`(d)
`
`with a non-self-aggregating uniform heterogeneity;
`
`forming the material into a film;
`
`applying the film to a substantially non—water soluble support; and
`
`drying the film in a controlled manner to maintain the non~self~
`
`aggregating uniform heterogeneity.
`
`In still another aspect of the present invention there is provided another method of
`
`administering an active including the steps of:
`
`(a)
`
`preparing dosage form by the steps of:
`
`(i)
`
`combining a polymer, an active component, and water to form a material
`
`with a non—self-aggregating uniform heterogeneity;
`
`(ii)
`
`forming the material into a film;
`
`(iii)
`
`applying the film to a substantially non‘water soluble support; and
`
`(iv)
`
`drying the film in a controlled manner to maintain the non-self-
`
`aggregating uniform heterogeneity;
`
`removing the film from said support; and
`
`applying the film to the oral cavity ofa mammal.
`
`(b)
`
`(c)
`
`Another aSpect ofthe invention provides a film product formed by the steps of:
`
`(a)
`
`combining a polymer and a liquid carrier to form a material with a non-self-
`
`aggrcgating uniform heterogeneity;
`
`(b)
`
`forming said material into a film; and
`
`
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`Page 10
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`55553;;
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`55.1155 “ii-“nil- :iil! '21-?" "if: -
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`(c)
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`removing said liquid carrier, for example, by evaporative methods or by
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`permitting volatilization to occur at selected temperatures, from said film in a
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`manner to maintain said non-self-aggregating uniform heterogeneity.
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`Also provided is a process for making a film having a substantially uniform distribution
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`of components including:
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`(a)
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`combining a polymer component and liquid carrier to form a matrix with a
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`(b)
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`(c)
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`uniform distribution of said components;
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`forming a film from said matrix; and
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`removing said liquid carrier, for example, by evaporative methods or by
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`permitting volatilization to occur at selected temperatures, from said film in a
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`manner to maintain said uniform distribution.
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`A still further aSpect ofthe present invention provides process for making a film having a
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`substantially uniform distribution of components including:
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`(a)
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`combining a polymer component and a polar solvent to form a matrix with a
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`uniform distribution of said components, said polymer selected to provide a
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`viscosity sufficient to maintain said uniform distribution; and
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`(b)
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`forming a- film from said matrix.
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`The invention also includes films and a process for preparing films having a substantially
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`uniform distribution of components. The process includes the steps of combining a polymer
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`component and water to form a uniformly distributed matrix. This matrix is then formed into a
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`film and fed onto a substrate surface having top and bottom sides where the bottom side is in
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`substantially uniform contact with a bottom drying medium, such as a water bath or heated air
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`space controlled at a temperature sufficient to dry the film. Desirably, no external air currents or
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`heat is applied directly to the exposed top surface ofthe film during the drying process until the
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`film structure has solidified sufficiently to prevent flow, migration and intermolecular attractive
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`forces from creating aggregates or conglomerates. Desirably the heat is controllably conducted
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`by the substrate surface to the film to effectuate drying. The matrix from which the film is
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`formed may also include an active ingredient. Also, either alternatively, or in addition to rapidly
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`a.- irzii H--l;'--”--ll-- 3255:: a" lit-nil!“
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`drying the film, the polymer may be selected in order to provide a viscosity that maintains the
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`non-self—aggregating uniform heterogeneity.
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`A pharmaceutical andfor cosmetic dosage form is also provided that includes a film
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`having a uniformly dispersed composition including a polymer, a pharmaceutical andfor
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`cosmetic active and a solvent, said film being formed by depositing a wet film of said
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`composition onto a substrate surface and controllably drying the wet film from the side
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`contacting the substrate to prevent self~aggregation and achieve compositional uniformity.
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`A still further aspect ofthc present invention includes a pharmaceutical and/or cosmetic
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`dosage form including a polymeric film having no more than a 10% variance ofa pharmaceutical
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`andfor cosmetic active per unit area.
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`The present invention also provides a pharmaceutical composition in the form ofa film
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`for external or topical administration, including a composition having a uniformly distributed
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`combination ofa polymer, a polar solvent, and a pharmaceutical active, said composition in its
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`dried film form maintaining the uniform distribution ofcomponcnts through the application of
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`controlled bottom drying ofthe film.
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`A pharmaceutical dispenser is also provided that includes individual unit dosage forms of
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`the pharmaceutical compositions and films ofthe present invention. The dosage forms may be
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`optionally stacked in a dispenser or in a roll.
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`Yet another aspect of the present inventi0n provides an ingestible water-soluble delivery
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`system in the form ofa film composition that includes a water-soluble polymer and an anti-
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`foaniing or defoaming agent, such as simethicone, which includes a combination of a
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`polymethylsiloxane and silicon dioxide. Simethicone can act as either an anti-foaming or
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`defoaming agent, or both, which reduces or eliminates air from the film composition. An anti-
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`foaming agent will aid in preventing the introduction of air into a composition, while a
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`defoaming agent will-aid in removing air from the composition. The composition may also
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`lizi‘r:
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`iii-l "- if" ”
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`include a pharmaceutical andfor cosmetic active ingredient, flavors, sweeteners, plasticizers,
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`surfactants, or other ingredients to alter the film properties to produce the desired product.
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`BRIEF DESCRIPTION OF THE DRAWINGS
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`Figure I shows a side view ofa package containing a unit dosage film of the present
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`invention.
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`Figure 2 shows a top view oftwo adj aeently coupled packages containing individual unit
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`dosage forms of the present invention, separated by a tearable perforation.
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`Figure 3 shows a side view ofthe adjacently coupled packages of Figure 2 arranged in a
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`stacked configuration.
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`Figure 4 shows a perspective view of a dispenser for dispensing the packaged unit dosage
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`forms, dispenser containing the packaged unit dosage forms in a stacked configuration.
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`Figure 5 is a schematic view ofa roll of coupled unit dose packages ofthe present
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`inventiOn.
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`Figure 6 is a schematic view of an apparatus suitable for preparation ofa premix,
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`addition ofan active, and subsequent formation of the film.
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`Figure 7 is a schematic view of an apparatus suitable for drying the films of the present
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`invention.
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`Figure 8 is a sequential representation of the drying prOCess ofthe present invention.
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`Figure 9 is a photographic representation ofa film dried by couventional drying
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`processes.
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`Figure 10 is a photographic representation oi'a film dried by conventional drying
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`processes.
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`11
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`iii: iiiii “-il-=“--ii-Iiiii 15"" “~35
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`.1”.
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`n.
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`Z
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`Figure l l is a photographic representation ofa film dried by conventional drying
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`p FOCCS S SS .
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`Figure 12 is a photographic representation ofa film dried by conventional drying
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`pTOCCSSCS.
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`Figure 13 is a photographic representation ofa film dried by conventional drying
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`processes.
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`Figure 14 is a photographic representation ofa film dried by conventional drying
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`processes.
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`Figure 15 is a photographic representation ofa filrn dried by conventional drying
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`processes.
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`Figure 16 is a photographic representation ofa film dried by conventional drying
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`processes.
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`Figure 17 is a photographic representation ofa film dried by the inventive drying process.
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`Figure 18 is a photographic representation ofa film containing fat coated particles dried
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`by the inventive drying process.
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`Figure 19 is a photographic representation ofa film containing fat coated particles dried
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`by the inventive drying process.
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`Figure 20 is a photographic representation ofa film containing fat coated particles dried
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`by the inventive drying process.
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`Figure 21 is a photographic representation ofa film containing fat coated particles dried
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`by the inventive drying process.
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`12
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`Page 14
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`Figure 22 is a photographic representation ofa fihn containing fat coated particles dried
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`by the inventive drying process.
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`Figure 23 is a photographic representation of a film containing fat coated particles dried
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`by the inventive drying process.
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`Figure 24 is a photographic representation of a film containing fat coated particles dried
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`by the inventive drying process.
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`Figure 25 is a photographic representation ofa film containing fat coated particles dried
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`by the inventive drying process.
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`Figure 26 is a photographic representation of fat coated particles not in film, heated for 9
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`minutes at 80°C.
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`Figure 27 is a photographic representation of fat coated particles not in film, heated for 9
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`minutes at 80"C.
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`Figure 28 is a photographic representation of fat coated particles at room temperature
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`prior to processing.
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`Figure 29 is a photographic representation of fat coated particles at room temperature
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`prior to processing.
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`Figure 30 is a photographic representation of fat coated particles at room temperature
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`prior to processing.
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`Figure 31 is a photographic representation of fat coated particles at room temperature
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`prior to processing.
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`at its: it lit-- -- .Ilt.
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`Hill Jill.
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`iii}: iiili till: Iii:
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`Figure 32 is a graphical representation of a microarray on the blood of a human after
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`ingestion by the human of a film of the present invention containing a bovine derived protein.
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`DETAILED DESCRIPTION OF THE INVENTION
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`For the purposes ofthe present invention the term non-self—aggregating uniform
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`heterogeneity refers to the ability of the films of the present invention, which are formed from
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`one or more components in addition to a polar solvent, to provide a substantially reduced
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`occurrence of, Le. little or no, aggregation or conglomeration of components within the film as is
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`normally experienced when films are formed by conventional drying methods such as a high-
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`temperature ai