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`Weight (g/dosage film)
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`Wettack (g)
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`0.028
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`0.001 (4)
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`a —
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`60.169
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`0.24 (2)
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`0.110 (6)
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`Ny ©
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`Tear-propagation resistance (N)
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`0.02
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`11.680 (6)
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`379 (5)
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`Examples4 - 8: Hydropropyimethylcellulose based quick dissolving intraoral film
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`The films were prepared according to Examples | - 3. Therapeutic agents were
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`added to the homogeneous mixture (coating solution) prior to forming the film.
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`-20-
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`Dr. Reddy's - EX1004
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`Dr. Reddy's - EX1004
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`Table 5:
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`Composition (coating
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`Table 6: Properties of the film formed according to the formulation in Table 5
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`Page 424
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`Table 7: Compostion of the Sildenafil film (%wetbase)
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`Dissolution (sec)
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`Example 9: A comparison of properties of dosage units using different
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`WO 00/42992
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`PCT/US99/31327
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`hydroxypropylmethvicellulose polymers
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`varying individual components. For example, the dissolution of the film may be
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`prolonged by using hydrox ypropyimethylcellulose (HPMC) with higher molecular
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`5 weight as shown below in Table 9.
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`Table 9a: Properties of selected commercial hydroxypropylmethylcellulose polymers.
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`Methocel Type (Dow Pharmaceuticals)
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`Isiowmomen!|o5[es[snes]ofasfse
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` Viscosity 2%
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`* Each value is the mean S+D, n=6
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`Page 426
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`FCFO'CT
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`[oeern[eee[emere|Pi
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`vfne[om[oo|eforme[ome
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`10°0F80°0(N)0uajsisayIvy,
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` 8CFIC9CeroTL(998)UONTOSsig
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`Culbe(998)UONeIsayuisiq
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`fefePepefefo|suatucjodasojnypaopAupaur|AdoidAxospAyiuasajyipSuisn‘7afdwuexg01Zurpsoosepauedaidsuayyjosansedolg:q¢3quy
`
`|ewee|oe[|awamewoeen
`cn|e[oe[me[omeaoe|[oe[|e
`sewe[oe[Pm
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`(isd)yysuansapisuay
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`Page 427
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`Increase in mucoadhesion %
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`results
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`Composition of
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`Starch graft
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`Mean
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`Example 10: Enhancement of mucoadhesion
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`The enhancement of mucoadhesion wassimilarly applicable to films of varying
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`thickness. The following formulations were prepared:
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`e Starch graft copolymers were prepared by polymerization in water using 1:3 Amioca
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`corn starch: acrylic acid (supplied by NSCC) and are described in further detail in US
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`ee Mucoadhesion wastested using a tensile instrument(e.g. Texture Analyzer) which
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`measures force of detachmentof the invention product from a simulated mucosaltissue
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`material. The mucosal-like material is prepared from a mixture of 3.25%gellan gum and
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`1.6% mucin in water. The productto be tested was brought into contact with the
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`simulated mucosal surface for 5 seconds and detached. The force of detachment was
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`measured as the value of mucoadhesion in gramsforce (g or gf). Test conditions used are
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`before detachment=150g, contact time=5s, contact surface =122.7mm-
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`- 26 -
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`Page 428
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`dosageunit are described in Table8.
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`Table 11. Figure 6 and Table 11 show that the bioavailability of the equivalent dosage
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`from the dissolving film is about 25% higher than the bioavailability of the tablet.
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`Tabie 11: A comparison of pharmacokinetic parameters of Sildanedil film and Viagra
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`film
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`Statistical
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`Pr[seassdorsfos
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`* Area under the curve
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`365.5
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`293.1
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`WO 00/42992
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`combining, in any order, in a vessel having a heating source and a
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`A dosage unit, comprising: an effective dose of sildenafil citrate; the
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`sildenafil citrate being formed in a solid dispersion with a water soluble inert filler, the
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`- 36 -
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`SUBSTITUTE SHEET (RULE26)
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`GINGIVA 2
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`UPPER LIP 1
`HARD PALATE 3
`SUBLINGUAL 6
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` CHEEK 4
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`LOWER LIP 7
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`SUBSTITUTE SHEET (RULE26)
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`yt480dLINN
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`ZtWildJILINNSaitzunsovoan
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`61didlSWilddalvuOsuad
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`Olg9+Z
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`(1!)SSANNOIHL
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`yOld
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`—-@—
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`JWINOLLVYSSINISIA
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`INLNOLMOSSIG—-O—
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`(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY(PCT)
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`(19) World Intellectual Property Organization
`International Bureau
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`(43) International Publication Date
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`27 September 2001 (27.09.2001)
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`(10) International Publication Number
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`WO 01/70194 Al
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`(51) International Patent Classification’: A61K 9/00, 9/20
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`(74) Agents: FEDERMAN,Evan, J.; Warner-Lambert Com-
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`pany, 201 Tabor Road, Morris Plains, NJ 07950 et al. (US).
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`(81) Designated States (national): AE, AG, AL, AU, BA, BB,
`BG, BR, BZ, CA, CN, CR, CU, CZ, DM, DZ, EE, GD, GE,
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`HR,HU,ID,IL, IN, IS, JP, KP, KR, LC, LK, LR,LT,LV,
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`MA, MG, MK, MN, MX, MZ, NO, NZ, PL, RO, SG, SL
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`SK, SL, TR, TT, UA, UZ, VN, YU, ZA.
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`(84) Designated States (regional): ARIPO patent (GH, GM,
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`KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZW), Eurasian
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`patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European
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`patent (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR,IE,
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`IT, LU, MC, NL, PT, SE, TR), OAPI patent (BF, BJ, CF,
`CG,CI, CM, GA, GN, GW, ML, MR,NE, SN, TD, TG).
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`Published:
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`with international search report
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`for two-letter codes and other abbreviations, refer to the "Guid-
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`ance Notes on Codes and Abbreviations" appearing at the begin-
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`ning ofeach regular issue of the PCT Gazette.
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`(21) International Application Number:
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`=PCT/US01/02192
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`(22) International Filing Date: 23 January 2001 (23.01.2001)
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`(25) Filing Language:
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`English
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`(26) Publication Language:
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`English
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`(30) Priority Data:
`09/535,005
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`23 March 2000 (23.03.2000)
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`US
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`COMPANY
`WARNER-LAMBERT
`(71) Applicant:
`[US/US]; 201 Tabor Road, Morris Plains, NJ 07950
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`(US).
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`(72) Inventors: BESS, William, S.; 31 Greenwish Road, Edi-
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`son, NJ 08820 (US). KULKARNI, Neema; 16 Wilkeshire
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`Boulevard, Randolph, NJ 07869 (US). AMBIKE, Suhas,
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`H.; 73 Charcoal Drive, West Hill, Ontario MIC 3T9 (CA).
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`RAMSAY,Michael, Paul; 45 Sayor Drive, Ajax, Ontario
`LIT 3K4 (CA).
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`ANUTATAA
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`194Al
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`@=> (54) Title: FAST DISSOLVING ORALLY CONSUMABLE FILMS CONTAINING AN ION EXCHANGERESIN AS A TASTE
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`~~ MASKING AGENT
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`(57) Abstract: Physiologically acceptable films, including edible films, are disclosed. The films include a water soluble film-form-
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`ing polymer, such as pullulan, and a taste masked pharmaceuticaliy active agent, such as dextromethorphan. The taste masking agent
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`is preferably a sulfonated polymer ion exchange resin comprising polystyrene cross-linked with divinylbenzene, such as AMBER-
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`LITE. Methods for producing the films are also disclosed.
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`Page 445
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