(12) United States Patent
`US 6,326,026 B1
`(10) Patent N0.:
`Parekh et al.
`(45) Date of Patent:
`*Dec. 4, 2001
`
`US006326026B1
`
`2,370,698
`2,373,721
`2,847,809
`
`,
`,
`3,185,626
`3,453,989
`3,538,997
`
`.
`
`3/1945 Vaughn .
`.
`4/1945 Taylor et a1.
`8/1958 Lindeman et al.
`Edd}?
`t
`1
`118/6
`ac man e a .
`...................... ..
`5/1965 Baker ................
`424/479
`
`7/1969 Bippus ........ ..
`118/503
`........................ .. 198 131
`11 1970 C t
`/
`a asaUqua
`/
`(List continued on next page.)
`
`FOREIGN PATENT DOCUMENTS
`1217140
`1/1987 (CA).
`1223209
`6/1987 (CA) .
`127081
`10/1928 (CH) .
`24 34 803 A1
`2/1975 (DE) .............................. .. A21C/9/04
`0 023 327
`1/1981 (EP).
`
`(List continued on next page.)
`OTHER PUBLICATIONS
`
`(54) SUBCOATED SIMULATED CAPSULE-LIKE
`MEDICAMENT
`
`(75)
`
`Inventors: Kishor B. Parekh, Horsham; Dennis
`-
`.
`Eéxfizngérfifipefibgggfi
`’
`y ’
`.
`.
`.
`(73) Assignee: McNell-PPC, Inc., Skillman, NJ (US)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U~S~C~ 154(b) byo days
`.
`.
`.
`.
`.
`Th1s patent 1s subject to a termmal d1s-
`claimer.
`
`(21) Appl‘ NO‘: 09/484,173
`(22)
`Filed:
`Jan. 14, 2000
`
`Related U-S- Application Data
`
`(60)
`
`Int. Cl.
`(51)
`(52) US. Cl.
`
`424/451’ 453
`
`(56)
`
`.
`References Clted
`US. pATENT DOCUMENTS
`
`,
`724,436
`1,115,426
`1,377,644
`
`:81?“d’
`1c ar 5.
`4/1903 Clark.
`10/1914 Green.
`5/1921 Warrington .
`
`Division of application No. 09/389,793, filed on Sep. 3,
`1999, now Pat. No. 6,214,350, which is a division of
`application No. 09/292,211, filed on Apr. 15, 1999, now Pat.
`No. 6,120,801, which is a division of application No.
`08/8023185, file 011.Feb~ 18, 19.97,.110W Pat N0~ 5,916,592,
`Single? gfofiéglllatlgg‘sflgg’hfifiwg
`{1516:
`continuation—in—part of application Nd. 07/345:599, filed on
`Apr. 28, 1989, now abandoned.
`7
`
`..................................................... .. A61K 9/48
`
`.. 424/463; 424/451; 424/453;
`424/456; 424/464; 424/474
`of Search .....................................
`
`
`
`
`
`_
`
`’
`
`_
`
`’
`
`Physician’s Desk Reference, Product Identification, PDR 32
`Edition, 1978, p. 438.
`~
`~
`2
`EgfiéluarllgsteSk
`1 10n’
`’ pp’
`1808—1809
`Porter, Stuart C., “Coating of Pharmaceutical Dosage
`Forms”, Remington’s Pharmaceutical Sciences, Chapt. 91,
`pp‘ 1633—1643, 17th Edmon’ MaCh Publ‘ CO‘ (1985)
`.
`.
`Przmary Exammer—Thurman K. Page
`Assistant Examiner_Lfliana Di N01a_Bar0n
`
`~
`
`_
`
`3:
`’ an
`
`ABSTRACT
`(57)
`Asimulated capsule_1fl(e medicament comprising a subcoat_
`ing of a mixture of a water-soluble, film-forming polymer,
`e.g. hydroxypropylmethyl cellulose and a hydrophobic
`plasticizer, e.g. castor oil, which promotes a smooth uniform
`and substantially bubble free outer coating, e.g. gelatin, for
`the capsule-like medicament; capsule-like medicaments
`which are slightly bowed in shape; and a process of making
`-
`suCh medlcamems‘
`
`8 Claims, 2 Drawing Sheets
`
`Mylan v. Qualicaps, |PR2017-00203
`QUALICAPS EX. 2023 - 1/9
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2023 - 1/9
`
`

`

`US 6,326,026 B1
`
`Page 2
`
`3,573,966
`3,896,762
`42227166
`4,526,129
`4,669,416
`4,684,113
`4,797,287
`4,816,259
`4,820,522
`4,820,524
`4,828,843
`4,851,230
`4,867,983
`4,880,101
`4,921,108
`4,965,089
`4,966,771
`4,990,358
`5,032,074
`5,054,258
`5,146,730
`5,155,981
`5,228,916
`
`5,234,099
`5,314,537
`5391230
`5,436,026
`5,466,290
`5,498,441
`5,503,673
`5,514,216
`5,607,044
`5,651,191
`6,120,801 *
`
`8/1993 Berta ............................. .. 198/803.01
`
`5/1994 Berta
`............................ .. 118/30
`2/1995 Pastecki et a1.
`................... N 118/503
`
`7/1995 Berta ...... N
`427/214
`11/1995 Berta .................................... .. 118/20
`3/1996 Berta ................................. .. 427/2.14
`
`4/1996 Berta
`118/16
`5/1996 Pastecki et a1.
`................... .. 118/503
`3/1997 Berta ............................... .. 198/468.4
`7/1997 Walunas et a1.
`34/236
`
`...................... .. 424/463
`9/2000 Parekh et a1.
`
`FOREIGN PATENT DOCUMENTS
`
`0 118 856 A1
`0 279 682 A3
`0 319 318
`0 194 502 B1
`0 246 693 A1
`2 588 888
`41—13997
`142947
`214983
`
`.............................. .. B07C/5/02
`
`9/1984 (EP)
`8/1988 (EP) .
`6/1989 (EP) .
`............................ .. G01N/33/52
`4/1990 (EP)
`.............................. .. A61K/9/48
`8/1992 (EP)
`4/1987 (FR) .............................. .. A61K/9/22
`8/1941 (JP) .
`3/1969 (NZ) .
`1/1986 (NZ) .
`
`* cited by examiner
`
`Mylan v. Qualicaps, |PR2017-00203
`QUALICAPS EX. 2023 - 2/9
`
`4/1971 Hostetler ............................ .. 117/100
`7/1975 Banker ................................. .. 118/30
`
`9/1980 Kurek etal-
`29/831
`7/1985 Braden ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ ~~ 118/503
`6/1987 Delgado et a1.
`................... .. 118/503
`8/1987 Douglas 9 al~
`269/21
`1/1989 Pich etal- ~~~~~~~~~~~~~~~~~~~~~~~~~~ ~~ 424/464
`3/1989 Matthews et a1.
`................. .. 424/464
`4/1989 Radebaugh etal-
`~~ 424/468
`4/1989 Berta .................................. .. 424/474
`5/1989 Pich et a1.
`.......................... .. 424/480
`.. 424/467
`7/1989 Tencza et a1.
`.
`
`9/1989 Berta .................................. .. 424/451
`11/1989 Wiggins ............................. .. 198/403
`.. 209/625
`5/1990 Berta ........ ..
`
`10/1990 Sauter et a1.
`427/3
`424/478
`10/1990 Berta ..... ..
`2/1991 Berta
`.... .. 427/3
`7/1991 Muto et a1
`.. 425/272
`10/1991 Tait et a1.
`. 53/137.2
`9/1992 Sadek et a1.
`53/454
`10/1992 Tordini
`. 53/559
`7/1993 Berta .................................... .. 118/30
`
`
`
`US. PATENT DOCUMENTS
`
`
`
`
`
`
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2023 - 2/9
`
`

`

`US. Patent
`
`Dec. 4, 2001
`
`Sheet 1 0f 2
`
`US 6,326,026 B1
`
`
`
`
`Mylan v. Qualicaps, |PR2017-00203
`QUALICAPS EX. 2023 - 3/9
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2023 - 3/9
`
`

`

`US. Patent
`
`Dec. 4, 2001
`
`Sheet 2 0f 2
`
`US 6,326,026 B1
`
`FIG. 3
`
`
`
`
`
`Mylan v. Qualicaps, |PR2017-00203
`QUALICAPS EX. 2023 - 4/9
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2023 - 4/9
`
`

`

`US 6,326,026 B1
`
`1
`SUBCOATED SIMULATED CAPSULE-LIKE
`MEDICAMENT
`
`This invention is a divisional application of US. Ser. No.
`09/389,793 filed Sep. 3, 1999, now Us. Pat. No. 6,214,350 5
`which is a divisional of Us. Ser. No. 09/292,211 filed Apr.
`15, 1999; U5. Pat. No. 6,120,801 which is a divisional
`application of U5. Ser. No. 08/802,185, filed Feb. 18, 1997,
`now US. Pat. No. 5,916,592; which is continuation of US.
`Ser. N0. 07/784,623, filed Oct. 31, 1991, now US. Pat. N0.
`5,658,589, which is a continuation-in-part of US. Ser. No.
`07/345,599 filed on Apr. 28, 1989, abandoned.
`
`
`
`2
`ance. A preferred gelatin-coated caplet is one in which two
`distinctly colored gelatin coating solutions are utilized to
`produce a bi-colored gelatin-coated caplet. The two over-
`lapping distinctly colored gelatin coatings form a seam
`about the transverse axis of the medicament. The presence of
`this seam and the distinct bi-coloring contributes to the
`consumer’s perception of these simulated capsule-like medi-
`caments as equivalents to gelatin capsule dosage forms.
`The gelatin coated caplet product must adequately simu-
`10 late a capsule-like medicament from a consumer’s sight and
`touch perspective and must
`therefore be absent of
`discoloration, pits and gouges. The presence of such physi-
`cal imperfections may erode the consumer’s perception as to
`the gelatin coated caplet’s capsule-like nature and the
`FIELD OF THE INVENTION
`This invention relates to subcoated simulated capsule-like 15 tamper-free hatiiie Of this dosage iOiih- StiOhg consumer
`medicaments. More particularly this invention relates to a
`COhhdehCe ih the geiatih capsiiie'iike hatiiie ahd tampei'
`solid medicament caplet core which has been subcoated with
`ieSiStahee 0f the Siihiiiated eaPshie medieaiheht 0f the
`a mixture of a water_sohib1e, fi1m_f0rmihg polymer and a
`invention is of the utmost importance in the marketing of
`hydrophobic plasticizer and coated with a smooth outer
`this dosage forth ahd forms ah Objeet 0f the Pieseht ihVeh'
`coating to provide the appearance of a capsu1e_hke inedi- 20 tion. It is therefore an object of the present invention to
`cament and a process of making such coated medicaments.
`PTOVide a siibeoatihg for a sOiid caPiet medicament core
`which minimizes bubble formation, discoloration and other
`aesthetic imperfections to provide for a smooth, uniform and
`BACKGROUND OF THE INVENTION
`Filled tw0_piece gelatin capsules for the encapsulation of 25 substantially bubble free outer coating appearance to simu-
`various medicinal agents have been used for administering
`lated Capsule'hke medlcamems’
`drugs since the mid-19th century. This capsule form of
`SUMMARY OF THE INVENTION
`medicament proved to be very popular because hard gelatin
`The foregoing object of providing a simulated capsule-
`capsules are tasteless, easily administered and easily filled
`either at a pharmacy 0r pre-filled in large quantities at 30 like medicament which has a smooth, uniform and substan-
`commercial plants. While hard shell gelatin capsules are still
`tially bubble free outer coating appearance has now been
`popular dosage forms for pharmaCist dispensed Inediea-
`accomplished in accordance with the compositions and
`ments they have generally been discontinued in many over-
`processes of the present invention.
`thetcounter products because of the risk of tampering w1th
`In accordance With the purposes of the invention, as
`their contents
`35 embodied and fully described herein, the invention com-
`Abseht the susceptibility 0i eaPshie forth medieaihehts t0
`prises a simulated capsule-like medicament comprising: a
`tamperings the Gapsnle form was extremely POPUIar With
`solid caplet core comprising a medicament; a subcoating
`consumers because of a number of advantages. Many con-
`composition on the caplet core cornprising a mixture of a
`sumers prefer the gelatin form of capsule because of the
`Water—soluble, filin-forining polyiner and a hydrophobic
`PeieeiVed efheaeya tastea ieei ahd swaiiowabiiity 0f the 40 plasticizer; and a smooth outer coating whereby the sub-
`geiatih capsiiie forth 0i medieaiheht-
`coating composition promotes a smooth, uniform and sub-
`This consumer preference for gelatin capsule-like medi-
`stantially bubble free outer coating appearance to the
`caments provided a challenge to the industry to produce
`capsule-like medicament.
`capsiiie'iike ihedieaihehts Whieh are tamper-Pie0f yet Pio'
`In another embodiment of the present invention, there is
`Vide the COhsiiihei With the adVahtages Of a hard Sheii gelatin 45 provided a swallowable solid core having a smooth, uniform
`capsiiie'iike dosage iOiih- Norbert i- Berta deVeiOPed Siihii'
`and substantially bubble free outer coating comprising a
`iated caPSUie'iike medicaments ahd a Process for makihg
`solid core containing a medicament which has an exterior
`such capsule-like medicaments as disclosed in his US. Pat.
`surface that is coated with a subcoating cornposed of a
`No. 4,820,524. The entire disclosure of this issued U.S.
`mixture of a water-soluble, film—forming polyrner selected
`patent is hereby incorporated herein by reference. Norbert I. 50 from the group consisting of hydroxypropyl cellulose,
`Berta has also developed variations of the processes for
`hydroxypropylmethyl cellulose, mixtures of hydroxypropyl
`makihg siihiiiated capsiiie'iike ihedieaihehts ahd apparatus
`cellulose and hydroxypropylmethyl cellulose, mixtures of
`for Piedueihg siiCh medieaihehts as diseiosed ih US Pat-
`hydroxypropyl cellulose and methyl cellulose wherein the
`N0. 4,921,108 filed DeC~ 4, 1987; US Pat- N0~ 4,966,771
`hydroxypropyl cellulose constitutes greater than 50 weight
`hied May 5, i988; ahd US- Pat- NO- 5,314,537 hied May 5, 55 percent but less than 100 weight percent of the mixture of
`1988- The siihiiiated capsiiie'iike ihedieaihehts deVeiOPed
`hydroxypropyl cellulose and methyl cellulose, mixtures of
`by Berta were responsive to a long felt need in the industry
`hydroxypropyl cellulose and hydroxyethyl cellulose
`to PiOVide a siihiiiated siibstitiite for the Popiiiai dosage forth
`wherein the hydroxypropyl cellulose constitutes greater than
`0i geiatih capsiiies- Whiie geiatih coatihg 0i hheoated COm'
`80 weight percent but less than 100 weight percent of the
`pressed medicaments such as acetaminophen is possible in 60 mixture of hydroxypropyl cellulose and hydroxyethyl
`accordance with the invention of Berta,
`it
`is difficult to
`cellulose, inixtures of hydroxypropylmethyl cellulose and
`control the quality of the surface appearance of such gelatin-
`methyl cellulose wherein the hydroxypropylmethyl celln_
`C0ated capletS.
`lose constitutes greater than 50 weight percent but less than
`Beyond the development of a simulated capsule-like
`100 weight percent of the mixture of hydroxypropylmethyl
`medicament several factors and considerations must be met 65 cellulose and methyl cellulose, mixtures of hydroxypropy-
`to commercially produce a capsule which has a smooth,
`lmethyl cellulose and hydroxyethyl cellulose wherein the
`uniform and substantially bubble free outer coating appear-
`hydroxypropylmethyl cellulose constitutes more than 80
`
`Mylan v. Qualicaps, |PR2017-00203
`QUALICAPS EX. 2023 - 5/9
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2023 - 5/9
`
`

`

`US 6,326,026 B1
`
`4
`
`5
`
`
`
`3
`weight percent but less than 100 weight percent of the
`Publishing Company (Fifteenth edition), 1975 the text of
`which is hereby incorporated by reference. Currently the
`mixture of hydroxypropylmethyl cellulose and hydroxyethyl
`cellulose and combinations of two or more thereof; and
`preferred solid core shapes for subcoating are solid core
`capsule-like shapes hereinafter referred to as caplets.
`castor oil, wherein the subcoating provides an outer subsur-
`To achieve one of the object of the invention Whioh is to
`face which is coated with a gelatinous coating, wherein the
`provide a simulated capsule-like medicament which has a
`subcoating is proVided in an amount Whieh is erreetiVe to
`smooth, uniform and substantially bubble-free outer coating
`prornote a srnootha uniform and snbstantiaiiy bubbie'rree
`appearance, a subcoating is applied to the solid caplet
`onter coating appearance to Capsnie'iike rnediearnents~
`medicament core to provide a compatible coating surface for
`In preferred embodiments of the invention the water-
`soluble,
`film-forming polymer
`is hydroxypropyl- 10 the gelatinous coating. The subcoating composition in accor-
`methylcellulose, the hydrophobic plasticizer comprises cas-
`dance with the invention provides a surface for gelatinous
`tor oil and the smooth outer coating composition is gelatin.
`coating that minimizes bubble formation, discoloration and
`In more preferred embodiments,
`the hydroxypropyl-
`other aesthetic imperfections.
`rnethyieeiiniose and eastor oii Cornprise rrorn about 2 to
`The capsule-like medicament of the invention comprises
`about 8%> more Preferably about 4 to about 6%> and rnost 15 a solid caplet core of a medicament which can be com-
`prererabiy about 4% by Weight or the totai Weight or the
`pressed into a caplet core utilizing conventional excipients
`subcoated Capiet core
`and tableting aids. Any pharmaceutical active or medica-
`In further preferred embodiments of the invention the
`ment that is capable of being formed into a caplet core, may
`medicament comprises a composition selected from the
`be used in accordance with the invention. Examples of
`group consisting of acetaminophen, ibuprofen, loperamide, 20 suitable medicaments which may be utilized in accordance
`naproxen, pseudoephedrine, dextromethorphan,
`with the invention include, but are not
`limited to,
`chlorphenarimine, and mixtures thereof.
`acetaminophen,
`ibuprofen,
`loperamide, naproxen,
`In further preferred embodiments a solid caplet core of the
`pseudoephedrinea deXtrornethorphana ehiorphenarirninea and
`capsule-like medicament has a slight convex bowed shape. 25 rnithres thereor- These inediearnents rnay be nsedaione or
`Preferably, the bow represents an arcuate variance of about
`in combination sneh as a sinus headaehe combination corn'
`1 to 5 degrees about a longitudinal axis of the caplet core.
`prising ror exarnpiea acetaminophen and pseudoephedrine-
`As embodied and broadly described herein the invention
`The subcoating Cornposition or the present inVention Was
`further comprises a process for preparing a simulated
`deveioped to proVide rnuitip1e hinetions required for a
`capsnieqike medicament comprising the steps of; compress- 30 suitable subcoat. These functions and characteristics of the
`ing a mixture of a medicament and pharmaceutically accept-
`subcoat or pre'eoat ineinde the roiioWing3 adequate hirn
`able exoipients to form a solid caplet oore; applying a
`strength of the subcoating to allow the subcoated tablet to
`subcoating composition comprising a mixture of a water-
`withstand mechanical transfer and maintain the integrity of
`sohihie, fi1m_forming polymer and a hydrophohiC plasticizer
`the subcoat; compatibility of the subcoat material with the
`to the solid caplet core; and applying a smooth outer coating 35 medicament
`to be coated; eornpatibiiity or the snbeoat
`to the subcoated caplet core to provide a smooth, uniform
`rnateriai With the srnooth outer coating sneh that adequate
`and substantially bubble free outer coating appearance to the
`piek'np or the srnooth onter coating is aehieVed With a
`capsule-like medicament. The preferred components for the
`minimum or bubbie formation on the hnai prodnet; and
`caplet core and the subcoating mixture are as described
`compatibility of the subcoat material with the outer coating
`above.
`In preferred embodiments of the process of the 40 such that the subcoat does not adversely affect the color of
`invention the outer coating is gelatin and is applied at a
`the outer coating Cornposition partieniariy Where tWo dis'
`temperature of from about 35 to 55° C., preferably at about
`tinet eoiors are ntiiizeri
`40 to 50° C.
`The subcoating composition of the invention also pro-
`vides advantageous processing functions. The subcoating
`45 helps eliminate dust and other degradation of the medica-
`BRIEF DESCRIPTION OF THE DRAWINGS
`them caplet Core' The subcoating also prevents Contamina'
`FIG. 1 is a front-top perspective view of a caplet core of
`tion of the gelatin coat1ng solution by the medicament
`the invention;
`present by prov1d1ng.a full separation.barr1er between the
`FIG. 2 is a top plan View of the caplet core;
`gelatin coating solution and the medicament 1n the sub-
`t
`t
`t
`.
`50 coated solid caplet core.
`FIG. 3 1s a side elevational View of the caplet core;
`In accordance with the present invention, it was found that
`FIG‘ 4 15 a front elevational View Of the caplet Core; and>
`a subcoating composition which accomplishes the required
`FIG. 5 is a top plan View Of a caplet 0f the prior art.
`£3?§::;;0‘i3$§:1::3 aah$§3£3b3§pia$1§32§°$iiéliai$fie
`DETAILED DESCRIPTION OF THE
`55 group of water-soluble film-forming polymers are cellulose
`PREFERRED EMBODIMENTS OF THE
`derivatives selected from the group consisting of hydrox-
`INVENTION
`ypropylmethyl cellulose (hereinafter also referred to as
`to preferred
`Reference will now be made in detail
`HPMC) and hydroxypropyl cellulose (hereinafter also
`embodiments of the invention, examples of which are illus-
`referred to as HPC) which may be used individually or
`trated in the following examples section. The present inven-
`tion provides a subcoating which is suitable for coating any 60 combined in mixtures. Hydroxypropylmethyl cellulose and
`swallowable solid core which will be subsequently coated
`hydroxypropyl cellulose may also be combined with other
`with a gelatinous outer layer. The solid core may be of any
`cellulose derivatives such as methyl cellulose and hydroxy-
`shape which is suitable for the oral administration of drug
`ethyl cellulose. The amount of HPMC and/or HPC present
`substances including but not limited to tablet or capsule
`in mixtures with methyl cellulose should be in the range of
`shapes. Suitable method of manufacturing solid cores are 65 from about 50 weight percent to less than 100 weight percent
`well known in the art such as the techniques on pages
`of HPMC and/or HPC based on the dry weight of the
`1576—1607 of Remington ’s Pharmaceutical Sciences, Mack
`components equalling 100 weight percent. The amount of
`
`Mylan v. Qualicaps, |PR2017-00203
`QUALICAPS EX. 2023 - 6/9
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2023 - 6/9
`
`

`

`US 6,326,026 B1
`
`
`
`5
`6
`tration of from in the range of about 20 weight percent to
`HPMC and/or HPC present in mixtures with hydroxyethyl
`cellulose should be in the range of from about 80 mole
`about 40 weight percent gelatin. The apparent viscosity of
`percent to less than 100 weight percent of HPMC and/or
`this gelatin solution is recommended to be in the range of
`HPC present in the mixture based on the dry weight of the
`from about 800 to about 1000 cps as measured at about 40°
`components of the mixture equalling 100 weight percent.
`5 C.—50° C.
`temperature on a Brookfield viscometer. The
`.
`t
`preferred gelatin for the practice of the present invention is
`The mOICculgr whlght 0f the Water'sduble film'
`.formmg
`a mixture of in the range of from about 60 weight percent to
`pOIYIhhrS unhzed m the Present Invennon 15.n0t beheved to
`about 80 Weight pemth of bone gelatin and in the range of
`be critical to the practice of the present invention. It is
`about 40 Weight percent t0 about 20 Weight percent of pork
`however recommended that the average molecular weight of
`the water'somble film'formmg polymer be m the range 0f 10 gelatin on a dry weight basis with the total weight percent of
`from about 50’000 to 150900 sultabk? grades 0f hydfox'
`the dry components totalling 100 weight percent. The cur-
`ypropylmethyl cellulose p01ymers Wlthm .these welght
`rently preferred gelatin mixture is 70 weight percent bone
`ranges may be obtained from Dow Chemical Company
`gelatin and 30 Weight pereent pork gelatin.
`deSIghated as E50. and E150 Chrrehhy preferred water_
`In preferred embodiments the capsule-like medicament of
`eelhble hhh fermlhg pelymere are hydrexyprepyhhethyl 15 the invention has a caplet core which has a slight convex
`cellulose pelymere haVIhg a meleehlar welght 0f about
`bowed sha e This sha e is illustrated in FIGS 1—4 herein
`50,000. The degree of substitution of the cellulose derivative
`which are ges'cribed in $10“: detail below This b'owed Shape
`hhhzed ih the Shbeeahhg Should eehferm to the degree 0f
`serves two im ortant functions It was found that ca lets of
`ShbShtthh approved for this use by the FDA' For example
`the prior art tlhat were unbowed or had straight edgejs were
`the degree of substitution of HPMC should be in the range 20 more
`rone to Stick to each other and form “twins ,, F0r_
`of from 19—30 percent methoxyl substitution and from 4—12
`mam”? of twins or twinnin is the .Oinin of one O'r more
`pereeht prepyl Shbethhheh ahd preferably ih the rahge 0f
`caplets together during proe3essing Jalonggedges in contact
`from 28—30 metheXyl pereeht hhd 7—.12 pereeht propyl'
`with each other. Further, caplets with straight edges also tend
`Methyl cellulose should be substituted in the range of from
`to Stick or twin together temporarily and cause surface
`275—315 hereeht .Ihethoey groups .The ehrrehhy preferred 25 imperfections, e.g. pitting and/or gouging. Twinning of
`hydrhphOblC pthhClzeh .15 Chetor 011' The amouht 0f Shb_
`straight edged prior art caplets is illustrated in FIG. 5 herein,
`coating SiomlilOSltlgn utlllZCd. shogldibe artiflamfcllunteffective1
`which is described in more detail below.
`to
`rov1 e t e a ove-mentione
`esira e
`nctions an
`Chahacteristics of the subcoated caplet core.
`Twinning of caplets can apply to any situation where the
`in aces;
`d
`r m;
`so 3:313:Crib:maygarner?3:33:23.“2,:
`articu ar me i-
`ance w1t
`t e size 0 t e ca et core an
`caments utilized. Preferably, Emixture of tlhe water-soluble
`ghfotsgecgggimlgotrh:SigggiggagnizlZEEEHSSO$31$331215
`film forming polymer (for example the preferred hydrox-
`.
`’
`.
`’
`.
`’
`.
`ypropylmethyl cellulose) and castor oil comprises from
`coanngs’ 0ft sufgar cotatlngs 211:5? ptrEVIdfe taCkg captlas Whlhh
`about 2 to about 8%, more preferably about 4 to about 6% 35 are prhne 9
`01H? dwms’
`1
`ere fire a Vin hgeous m
`byof
`.
`.
`’
`o
`t e su coate
`cap et core. T e amount 0
`castor oi
`f
`.
`the;
`a; a
`afltakzgmzzr :2£22:i:;§:::gw:féa:t;: 2:1ng
`0.1toaoutlo weitotetotaweitote
`subcoated caplet coere. Preferably the amountgof water- 40 cohtact during processmg’ The bowed Shape minimizes the
`soluble film_f0rming polymer e.g. hydroxypropylmethyl
`point of corfitact bettvxteen caplet: and thus reduces sticking or
`cellulose, to the hydrophobic plasticizer e.g. castor oil, is on
`Wlnmng 0 cap 6 S 0 teac
`0 er‘
`.
`t
`the order of about 20:1.
`In. preferred embodiments of the present invention, the
`It is important that the outer coating of the simulated
`bowtng .15 a CQHVCX bow that Stems from the Huddle Of a
`capsule_hke medicament be smooth, uniform and subStan_ 45 longitudinal ax1s of the caplet core outwards towardtthe two
`tiafly bubble free t0 provide the perception of a capsu1e_hke
`ends. The bowed variance along the longitudinal ax1s of the
`medicament. To achieve superior simulation of gelatin cap-
`caplet coreds on. the order 0f about 1 to 5 degrees; Thls
`sule dosage forms it is preferred to use a dual color outer
`arcuate Varlanch 15 great ehoughlo reduce the. twmmng 0f
`coating which meets at a distinct seam at about the middle
`the caplets durmg processmg Wlthout detracnng frpm the
`of the coated medicament caplet. The preferred outer coating 50 capsule'hke. Shape .and appearanhe of the final medlcameht
`composition is gelatin whereby the subcoated caplet core is
`prOduCt Wthh 15 Important to us Slmulanon Of a gelatm
`dipped into a gelatinous solution. More preferably opposite
`capsule‘
`ends of a subcoated medicament caplet core are dipped into
`AnOther surprising adVantage 0f prOViding caPlets With a
`two gelatinous solutions of distinct color to produce a dual
`slightly C0nVeX bowed Shape is that the shape proVides an
`colored capsule-like medicament. The amount of gelatinous 55 increase in tablet hardness 0f up to about 10% as compared
`coating added to the product is dependent upon the outer
`with regular unbowed caplet shaped cores. The increase in
`appearance desired for
`the product. Generally, enough
`hardness may be due to some degree to the increased
`gelatinous coating must be added on to the caplet to provide
`thickness of the caplet about the center area but the magni-
`a smooth uniform and bubble free outer coating appearance
`tude of increase achieved could not be anticipated by this
`and provide a gelatinous feel to the touch and in the mouth 60 slight change in thickness at this area. It has also been found
`of consumers swallowing the simulated capsule-like medi-
`adVantageons to prOVide a conVeX boW shaped caplet since
`carnent. Apreferred gelatinous coating add—on is about 6.0
`the increased hardness contributes to preventing surface
`to about 8.3% by weight of the total weight of the simulated
`pitting and breaking 0f the cores during the coating process.
`caPSllle-like medicament.
`The bow shaped caplet core of the invention will now be
`It is also recommended that the gelatin coating utilized in 65 described with reference to the Figures herein. FIG. 1 is a
`the present
`invention for coating the caplet surface be
`perspective view of a caplet core (1) from the top (3), front
`provided in an aqueous solution having a gelatin concen-
`(5) and right (7) sides. A peripheral edge surface or “belly
`
`Mylan v. Qualicaps, |PR2017-00203
`QUALICAPS EX. 2023 - 7/9
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2023 - 7/9
`
`

`

`7
`
`US 6,326,026 B1
`
`
`
`8
`and more preferably a bicolor gelatin coating. Application of
`band” (9) extends longitudinally around the side of the
`the gelatinous coating is by dipping of the subcoated caplet
`caplet core
`FIG. 2 shows a top plan view of the caplet
`core into a gelatin solution which has a temperature in the
`core (1) with adjacent caplet cores (11) shown in broken
`range of about 35—55° C., preferably about 40 to 50° C.
`lines on either side of the caplet core (1) at their belly bands
`5 Higher gelatin solution temperatures generally result in a
`(9) and (13). In accordance with the slight bowed shape of
`lower viscosity of the gelatin solution. The gelatin solution
`the belly bands (9) and (13) the adjacent caplet cores have
`temperature is varied to adjust the viscosity and gelatin
`only a single point of contact (15) with each other along the
`pick-up on the subcoated caplet.
`arcuate edge surface of the belly band. The amount of
`Gelatin dipping may be performed by any adequate means
`bOWihg heed Ohiy be Slighta Oh the order 0f 1 t0 5 degrees
`a5 is ihhStiated by ahgie V ih the diaWihg- FIG- 3 is a Side 10 including hand dipping of the caplets into a gelatin solution.
`eieVatiOhai View Of the caplet core (1) and belly band
`Aparticularly preferred method is performed in accordance
`FIG 4 is a front eieVatiOhai View Of the caplet core (1) and
`with the teachings of Berta in the aforementioned US. Pat.
`behy bahd
`No. 4,820,524 which has been incorporated herein by ref-
`FIG. 5 is a view similar to FIG. 2 showing a straight edged
`erence. This patent provides a useful process for providing
`or unbowed caplet core (50) of the prior art with adjacent or 15 bi-color gelatin coated capsule-like medicaments which
`twinned caplet cores (52) in contact therewith along straight
`have a slightly raised seam about the color overlapping
`edged belly bands (54) with a point of contact along the
`portion of the caplet which contributes to its simulated
`entire straight edge of the caplet core as illustrated by the
`capsule-like feel and appearance.Any color gelatin solutions
`dimension (56) marked out by length indicators (58) and
`may be utilized, but it is preferred that the colors be distinct.
`(60). This large potential area of contact along the entire 20
`straight edge (56) of caplet cores of the prior art encourages
`sticking or twinning of caplets to each other and production
`of surface imperfect or twinned caplets which are not
`suitable for further commercial use as simulated capsule-like
`medicaments.
`In accordance with the present invention, aprocess is also
`provided for preparing simulated capsule-like medicaments.
`.
`.
`.
`.
`.
`The process comprises the steps of compressing a mixture of
`medicament and compatible exc1pients to form a solid caplet
`core. The excipients chosen and the compression applied 30
`should be adequate to provide a caplet with sufficient
`hardness for prevention of surface pitting and caplet break-
`.
`.
`.
`age during coating of the caplet core. For capsule-like
`acetaminophen medicaments the preferred hardness is about
`10—14 Kp and more preferably about 10—11 Kp.
`To provide a capsule shape appearance the width to
`thickness ratio about the simulated capsule-like medicament
`.
`ctive and Exc1pients
`.
`A .
`I
`should be as close as possible to one. Gelatin capsule dosage
`.
`.
`forms are generally round in shape and therefore have a 40 —
`width to thickness ratio by definition of one. A preferred
`acetaminophen, USP
`tooling dimension which gives this appearance is 0.750
`POWdeiedFehuiOSe NF
`inches by 0.250 inches by 0.075 inches. The thickness
`pregelaumzed Starch’ NF
`.
`.
`.
`.
`.
`.
`.
`sodium starch glycolate, NF
`1L
`resulting from this tooling is 0.244 inches. These dimens10ns
`Granulatng Agent
`may vary as the size of the caplet varies but efforts should 45 —
`be made to keep the width to thickness ratios as close as
`Starch: NF
`purified water, USP
`~
`~
`~
`~
`~
`
`Dry Adds
`possible to one to prov1de adequate simulation of a gelatin
`capsule dosage form.
`The subcoating composition, preferably a mixture of
`hydroxypropylmethyl cellulose and castor .oil,
`is applied 50
`from an 8% weight by weight aqueous solution. Acceptable
`subcoatings can be applied with subcoating solutions of
`Working Directions
`from 6 to 8% concentration. but.8% is. preferred since a
`.
`.
`.
`shorter amount of spraying time is required to prov1de the
`desired amount of subcoating on the caplet core. Coating 55 A weigh the deSHed ComPOhehtS 0f Part1 1h the PTOPOi'
`levels above 8% were found to provide less desirable
`tiOhS PTOVided ahd add them to a b0Wi Of a hhid bed
`subcoatings because of unevenness of application of the
`grahulator Sheh as ah AEROMATIC brahd grahulator-
`subcoating composition. The concentration of the subcoat-
`B. Prepare the granulating agent (Part II) by adding the
`ing solution is not considered critical to the coating process.
`purified water to a processing tank with approximately 15
`The caplet cores are subcoated to preferably provide about 60 grams of water for each gram of starch NF. Slowly mix in
`2 to 8%, more preferably about 4 to 6 and most preferably
`the starch and heat the mixture until the temperature reaches
`about 4% subcoating by weight of the total weight of the
`about 82—84° C.
`Slle0ated caplet C0re.
`C. With the components of Part I in a heated fluidized
`Asmooth