Organization
`
`International Bureau
`
`=z
`Soe=\
`
`(43) International Publication Date
`30 May 2013 (30.05.2013)
`
`WIPO!) PCT
`
`(51)
`
`International Patent Classification:
`C07D 405/12 (2006.01)
`A61K 31/496 (2006.01)
`
`(21)
`
`International Application Number:
`
`PCT/US2012/066324
`
`(74)
`
`(81)
`
`(22)
`
`International Filing Date:
`21 November 2012 (21.11.2012)
`
`(25)
`
`Filing Language:
`
`MAMTACTRNAAA
`
`(10) International Publication Number
`WO 2013/078361 Al
`
`Agents: BIRDE, Patrick, J. et al.; Kenyon & Kenyon
`LLP, One Broadway, New York, NY 10004-1050 (US).
`
`Designated States (unless otherwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY,
`BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM,
`DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM,GT,
`HN, HR, HU,ID,IL, IN, IS, JP, KE, KG, KM, KN, KP,
`KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD,
`ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI
`NO, NZ, OM,PA, PE, PG, PH, PL, PT, QA, RO, RS, RU,
`RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ,
`TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA,
`ZM, ZW.
`
`(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY(PCT)
`(19) World Intellectual Property
`=
`
`English
`
`English
`
`US
`US
`US
`US (g4)
`US
`US
`US
`US
`US
`
`Publication Language:
`
`Priority Data:
`61/563,150
`23 November 2011 (23.11.2011)
`61/583,368
`5 January 2012 (05.01.2012)
`61/584,499
`9 January 2012 (09.01.2012)
`61/590,412
`25 January 2012 (25.01.2012)
`61/637,416
`24 April 2012 (24.04.2012)
`61/651,221
`24 May 2012 (24.05.2012)
`61/653,778
`31 May 2012 (31.05.2012)
`61/670,895
`12 July 2012 (12.07.2012)
`61/717,351
`23 October 2012 (23.10.2012)
`
`(26)
`
`(30)
`
`(71)
`
`(71)
`
`(72)
`(71)
`
`Applicant (for all designated States except US): ASSIA
`CHEMICAL INDUSTRIES LTD.
`[IL/IL]; 2 Denmark
`Street, 49517 Petach Tikva(IL).
`
`Applicant (or BB only): TEVA PHARMACEUTICALS
`USA, INC [US/US]; 1090 Horsham Road, P.0. Box 1090,
`North Wales, PA 19454-1090 (US).
`
`Inventors; and
`Applicants (for US only): LEKSIC, Edislav [HR/HR];
`Selska Cesta 90g, 10000 Zagreb (HR). PAVLICIC, Dub-
`ravka [HR/HR];
`I. FerenScica 59, 10000 Zagreb (HR).
`SKALEC SAMEC,Dijana [HR/HR]; Malunje 5, 10450
`Jastrebarsko (HR). DOGAN, Jasna [HR/HR]; Dobrise
`Cesarica 4c, 0090 Zagreb
`(HR). MRSIC, Natasa
`[HR/HR]; Grge Novaka 17, 10361 Sesvetski Kraljevec,
`Croatia (HR).
`
`Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ,
`UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU,TJ,
`TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK,
`EE, ES, FI, FR, GB, GR, HR, HU,IE,IS, IT, LT, LU, LV,
`MC, MK,MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM,
`TR), OAPI (BF, BJ, CF, CG, CL, CM, GA, GN, GQ, GW,
`ML, MR,NE, SN, TD, TG).
`Declarations under Rule 4.17:
`
`as to the applicant's entitlement to claim the priority of the
`earlier application (Rule 4.17(iii))
`Published:
`
`with international search report (Art. 21(3))
`
`before the expiration of the time limit for amending the
`claims and to be republished in the event of receipt of
`amendments (Rule 48.2(h))
`
`(54) Title: SOLID STATE FORMS OF VILAZODONE AND VILAZODONE HYDROCHLORIDE
`
`(57) Abstract: The present invention provides solid state forms of Vilazodone and Vilazodone hydrochloride, processes for prepar -
`ing these solid state forms, and pharmaceutical compositions comprising one or more ofthese solid state forms
`
`Merck 2015
`Merck 2015
`Argentum v. Merck
`Argentum v. Merck
`IPR2018-00423
`IPR2018-00423
`
`wo2013/078361A|IINTINITNINNMNTTAIAITATTATANTATTAUT
`
`

`

`WO2013/078361
`
`PCT/US2012/066324
`
`SOLID STATE FORMS OF VILAZODONE AND VILAZODONE
`
`HYDROCHLORIDE
`
`CROSS REFERENCE TO RELATED APPLICATIONS
`
`[0001]
`
`The present invention claims the benefit of the following United States
`
`Provisional Patent Application Nos.: 61/563,150, filed November 23, 2011; 61/583,368, filed
`
`January 5, 2012; 61/584,499, filed January 9, 2012; 61/590,412, filed January 25, 2012;
`
`61/637,416, filed April 24, 2012; 61/651,221, filed May 24, 2012; 61/653,778, filed May 31,
`
`2012; 61/670,895, filed July 12, 2012; and 61/717,351, filed October 23, 2012. The contents
`
`of these applications are incorporated herein by reference.
`
`FIELD OF THE INVENTION
`
`[0002]
`
`The invention relates to solid state forms of Vilazodone and Vilazodone
`
`hydrochloride, processes for preparing these solid state forms, and pharmaceutical
`
`compositions comprising one or moreof these solid state forms.
`
`BACKGROUNDOF THE INVENTION
`
`[0003]
`
` Vilazodone, 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin- 1-yl)benzofuran-2-
`
`carboxamide, has the following chemicalstructure:
`
`NH;
`Ss
`NC/\
`O
`N
`N
`
`\_/or
`
`NH
`
`[0004]
`
`-Vilazodone (HCI salt marketed as VIIBRYD)is an SSRI antidepressant(selective
`
`serotonin reuptake inhibitor and a 5HT), receptor partial antagonist) developed for the
`
`treatment of major depressive disorder. The compound wasoriginally developed by Merck
`
`KGaA, Germany, and is now ownedby Forest Laboratories Inc, USA.
`
`[0005]
`
`A synthesis of Vilazodoneis described in US Patent No. US 5,532,241.
`
`

`

`WO2013/078361
`
`PCT/US2012/066324
`
`[0006]
`
`Certain crystalline forms of Vilazodone hydrochloride, and of Vilazodone
`
`dihydrochloride are described in the PCT Publication No. WO2002102794.
`
`[0007]
`
`Polymorphism, the occurrence of different crystal forms, is a property of some
`
`molecules and molecular complexes. A single compound maygiverise to a variety of
`
`polymorphshavingdistinct crystal structures and physical properties like melting point,
`
`thermal behaviors (e.g., measured by thermogravimetric analysis — “TGA”, or differential
`
`scanning calorimetry — “DSC”’), powder X-ray diffraction (XRD)pattern, infrared absorption
`
`fingerprint, and solid state NMR spectrum. One or more of these techniques may be used to
`
`characterize a particular polymorph andto distinguish different polymorphic formsof a
`
`compound.
`
`[0008]
`
`Discovering new polymorphic forms(including newsolvates) of a pharmaceutical
`
`product can provide materials having, inter alia, desirable processing properties, such as ease
`
`of handling, ease of processing, chemical and polymorphicstability upon storage and
`
`processing, and ease ofpurification, or are useful as intermediate crystal formsthat facilitate
`
`conversion to other polymorphic formsor salts of a pharmaceutical compound. New
`
`polymorphic formsandsolvates of a pharmaceutically useful compoundorsalts thereof can
`
`also provide opportunities to improve the performance characteristics of a pharmaceutical
`
`product. They can also enlarge the repertoire of materials available to a formulation scientist
`
`for formulation optimization, for example by providing a product with different properties,
`
`e.g., better processing or handling characteristics, improved dissolution profile, or improved
`
`shelf-life. Lastly, new polymorphic forms may be prepared with improvedreliability and
`
`reproducibility compared to other forms, for example in termsofcrystallinity or polymorphic
`
`purity. For at least these reasons, there is a need for additional polymorphsof Vilazodone
`
`and its hydrochloride salt.
`
`SUMMARY OF THE INVENTION
`
`[0009]
`
`The present invention provides newsolid state forms of Vilazodone. These solid
`
`state forms can inter alia be used to preparesalts, particularly Vilazodone hydrochloride,
`
`solid state forms of those salts and pharmaceutical compositions and formulationsthereof.
`
`[0010]
`
`The present invention also provides new solid state forms of Vilazodone
`
`hydrochloride. These solid state forms can be used to prepare pharmaceutical compositions
`
`

`

`WO2013/078361
`
`PCT/US2012/066324
`
`and formulations thereof, or they can be used to prepare Vilazodone free base and/or other
`
`salts of Vilazodone and/or formulations thereof.
`
`[0011]
`
`The invention further providesthe solid state forms of Vilazodone and of
`
`Vilazodone hydrochloride as described herein for use in the manufacture of a medicament,
`
`preferably for the treatment of major depressive disorders; and provides a methodoftreating
`
`major depressive disorders, said method comprising administering a therapeutically effective
`
`dose of one or more of the solid state forms described herein.
`
`BRIEF DESCRIPTION OF THE FIGURES
`
`[0012]
`
`Figure 1 provides a powder XRD pattern of crystalline Form A of Vilazodone.
`
`[0013]
`
`Figure 2 provides a DSC thermogram ofcrystalline Form A of Vilazodone.
`
`[0014]
`
`Figure 3 provides a powder XRD pattern of crystalline Form B of Vilazodone.
`
`[0015]
`
`Figure 4 provides a DSC thermogram ofcrystalline Form B of Vilazodone.
`
`[0016]
`
`Figure 5 provides a powder XRD pattern of crystalline Form C of Vilazodone.
`
`[0017]
`
`Figure 6 provides a DSC thermogram ofcrystalline Form C of Vilazodone.
`
`[0018]
`
`Figure 7 provides a powder XRD pattern of crystalline Form D of Vilazodone.
`
`[0019]
`
`Figure 8 provides a DSC thermogram ofcrystalline Form D of Vilazodone.
`
`[0020]
`
`Figure 9 provides a powder XRD pattern of crystalline Form E of Vilazodone.
`
`[0021]
`
`Figure 10 provides a DSC thermogram of crystalline Form E of Vilazodone.
`
`[0022]
`
`Figure 11 provides a powder XRD pattern of crystalline Form F of Vilazodone.
`
`[0023]
`
`Figure 12 provides a DSC thermogram ofcrystalline Form F of Vilazodone.
`
`[0024]
`
`Figure 13 provides a powder XRD pattern of crystalline Form G of Vilazodone.
`
`[0025]
`
`Figure 14 provides a powder XRD pattern of crystalline Form H of Vilazodone.
`
`[0026]
`
`Figure 15 provides a powder XRD pattern of crystalline Form I of Vilazodone.
`
`[0027]
`
`Figure 16 provides a powder XRD pattern of amorphous Vilazodone.
`
`[0028]
`
`Figure 17 provides a DSC thermogram of amorphous Vilazodone.
`
`[0029]
`
`Figure 18 provides a powder XRD pattern of amorphous Vilazodone.
`
`[0030]
`
`Figure 19 provides a DSC thermogram of amorphous Vilazodone.
`
`

`

`WO2013/078361
`
`PCT/US2012/066324
`
`[0031]
`
`Figure 20 provides a powder XRD pattern of crystalline Form E1 of Vilazodone.
`
`[0032]
`
`Figure 21 provides a DSC thermogram ofcrystalline Form E1 of Vilazodone.
`
`[0033]
`
`Figure 22 provides a powder XRD pattern of crystalline Form Al of Vilazodone.
`
`[0034]
`
`Figure 23 provides a DSC thermogram ofcrystalline Form Al of Vilazodone.
`
`[0035]
`
`Figure 24 provides a powder XRD pattern ofcrystalline Form Alpha of
`
`Vilazodone hydrochloride.
`
`[0036]
`
`Figure 25 provides a DSC thermogram ofcrystalline Form Alpha of Vilazodone
`
`hydrochloride.
`
`[0037]
`
`Figure 26 provides a powder XRD pattern of crystalline Form Beta of Vilazodone
`
`hydrochloride.
`
`[0038]
`
`Figure 27 provides a DSC thermogram ofcrystalline Form Beta of Vilazodone
`
`hydrochloride.
`
`[0039]
`
`Figure 28 provides a powder XRD pattern of crystalline Form Gammaof
`
`Vilazodone hydrochloride.
`
`[0040]
`
`Figure 29 provides a DSC thermogram ofcrystalline Form Gammaof Vilazodone
`
`Hydrochloride.
`
`[0041]
`
`Figure 30 provides a powder XRD pattern of crystalline Form Delta of Vilazodone
`
`hydrochloride.
`
`[0042]
`
`Figure 31 provides a DSC thermogram ofcrystalline Form Delta of Vilazodone
`
`hydrochloride.
`
`[0043]
`
`Figure 32 provides a powder XRD pattern ofcrystalline Form Epsilon of
`
`Vilazodone hydrochloride.
`
`[0044]
`
`Figure 33 provides a DSC thermogram ofcrystalline Form Epsilon of Vilazodone
`
`hydrochloride.
`
`[0045]
`
`Figure 34 provides a powder XRD pattern of crystalline Form Eta of Vilazodone
`
`hydrochloride.
`
`[0046]
`
`Figure 35 provides a DSC thermogram ofcrystalline Form Eta of Vilazodone
`
`hydrochloride.
`
`

`

`WO2013/078361
`
`PCT/US2012/066324
`
`[0047]
`
`Figure 36 provides a powder XRD pattern of crystalline Form Theta of Vilazodone
`
`hydrochloride.
`
`[0048]
`
`Figure 37 provides a DSC thermogramofcrystalline Form Theta of Vilazodone
`
`hydrochloride.
`
`[0049]
`
`Figure 38 provides a powder XRD pattern of crystalline Form Iota of Vilazodone
`
`hydrochloride.
`
`[0050]
`
`Figure 39 provides a DSC thermogram ofcrystalline Form Iota of Vilazodone
`
`hydrochloride.
`
`[0051]
`
`Figure 40 provides a powder XRD pattern ofcrystalline Form Kappaof
`
`Vilazodone hydrochloride.
`
`[0052]
`
`Figure 41 provides a powder XRD pattern of crystalline Form Lambda of
`
`Vilazodone hydrochloride.
`
`[0053]
`
`Figure 42 provides a DSC thermogram ofcrystalline Form Lambda of Vilazodone
`
`hydrochloride.
`
`[0054]
`
`Figure 43 provides a powder XRD pattern of crystalline Form Mu of Vilazodone
`
`hydrochloride.
`
`[0055]
`
`Figure 44 provides a powder XRD pattern of crystalline Form Nu of Vilazodone
`
`hydrochloride.
`
`[0056]
`
`Figure 45 provides a powder XRD pattern of amorphous Vilazodone
`
`hydrochloride.
`
`[0057]
`
`Figure 46 provides a powder XRD pattern of amorphous Vilazodone
`
`hydrochloride.
`
`[0058]
`
`Figure 47 provides a DSC thermogram of amorphous Vilazodone hydrochloride.
`
`[0059]
`
`Figure 48 provides a DSC thermogram of amorphous Vilazodone hydrochloride.
`
`[0060]
`
`Figure 49 provides a powder XRD pattern of a solid dispersion of Vilazodone
`
`hydrochloride and polyvinylpyrrolidone (PVP).
`
`[0061]
`
`Figure 50 provides a powder XRD pattern of a solid dispersion of Vilazodone
`
`hydrochloride and hydroxypropyl methylcellulose (HPMC).
`
`

`

`WO 2013/078361
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`PCT/US2012/066324
`
`[0062]
`
`Figure 51 provides a powder XRD pattern of Form Zeta of Vilazodone
`
`hydrochloride.
`
`[0063]
`
`Figure 52 provides a DSC thermogram of Form Zeta of Vilazodone hydrochloride.
`
`[0064]
`
`Figure 53 provides a DSC thermogram of Form Xi of Vilazodone hydrochloride.
`
`[0065]
`
`Figure 54 provides a DSC thermogram of Form XI of Vilazodone hydrochloride.
`
`[0066]
`
`Figure 55 provides a powder XRD pattern of Form Omicron of Vilazodone
`
`hydrochloride.
`
`[0067]
`
`Figure 56 provides a DSC thermogram of Form Omicron of Vilazodone
`
`hydrochloride.
`
`[0068]
`
`Figure 57 provides a powder XRD pattern of Form Pi of Vilazodone
`
`hydrochloride.
`
`[0069]
`
`Figure 58 provides a DSC thermogram of Form Pi of Vilazodone hydrochloride.
`
`[0070]
`
`Figure 59 provides a powder XRD pattern of Form Rho of Vilazodone
`
`hydrochloride.
`
`[0071]
`
`Figure 60 provides a DSC thermogram of Form Rho of Vilazodone hydrochloride.
`
`[0072]
`
`Figure 61 provides a powder XRD pattern of Form Sigma of Vilazodone
`
`hydrochloride
`
`[0073]
`
`Figure 62 provides a powder of Form K of Vilazodone.
`
`[0074]
`
`Figure 63 provides a DSC thermogram of Form K of Vilazodone.
`
`[0075]
`
`Figure 64 provides a powder XRD pattern of Form L of Vilazodone.
`
`[0076]
`
`Figure 65 provides a DSC of Form L of Vilazodone.
`
`[0077]
`
`Figure 66 provides a powder XRD pattern of Form M of Vilazodone.
`
`[0078]
`
`Figure 67 provides a DSC thermogram of Form Muof Vilazodone HCl.
`
`[0079]
`
`Figure 68 provides a Raman spectrum of Form Alpha of Vilazodone HCl.
`
`[0080]
`
`Figure 69 provides a Ramanspectrum of Form Muof Vilazodone HCl
`
`[0081]
`
`Figure 70 provides a Raman spectrum of Form Lambda of Vilazodone HCI.
`
`[0082]
`
`Figure 71 provides a powder XRD pattern of Form Tau of Vilazodone HCI.
`
`

`

`WO2013/078361
`
`PCT/US2012/066324
`
`DETAILED DESCRIPTION OF THE INVENTION
`
`[0083]
`
`The present invention provides newsolid state forms of Vilazodone and of
`
`Vilazodone hydrochloride. These solid state forms can, for example, be used to prepare salts
`
`and/or formulations thereof.
`
`[0084]
`
`As used herein, the term "Vilazodone"refers to Vilazodonefree base.
`
`[0085]|A polymorph maybereferred to herein as substantially free of any other solid
`
`forms. As used herein in this context, the expression “substantially free” will be understood
`
`to mean that the solid state form contains 20% or less, 10% or less, 5% or less, 2% or less, or
`
`1% or less of any other solid form of the subject compound as measured, for example, by
`
`powder X-ray diffraction (PXRD). Thus, polymorphs of Vilazodone described herein as
`
`substantially free of any other solid forms would be understood to contain greater than 80%
`
`(w/w), greater than 90% (w/w), greater than 95% (w/w), greater than 98% (w/w), or greater
`
`than 99% (w/w) of the subject form of Vilazodone. Accordingly, in some embodiments of
`
`the invention, the described polymorphs of Vilazodone may contain from 1% to 20% (w/w),
`
`from 5% to 20% (w/w), or from 5% to 10% (w/w) of one or more other solid forms of
`
`Vilazodone.
`
`[0086]
`
`A solid state form may bereferred to herein as being characterized by graphical
`
`data “as shown in” a Figure. Such data include, for example, powder X-ray diffractograms
`
`and solid state NMRspectra. The graphical data potentially provides additional technical
`
`information to further define the respective solid state form which can not necessarily be
`
`described by reference to numerical values or peak positions. In any event, the skilled person
`
`will understand that such graphical representations of data may be subject to small variations,
`
`e.g., in peak relative intensities and peak positions due to factors such as variations in
`
`instrument response and variations in sample concentration and purity, which factors are well
`
`knownto the skilled person. Nonetheless, the skilled person would readily be capable of
`
`comparing the graphical data in the Figures herein with graphical data generated for an
`
`unknowncrystal form and confirming whether the two sets of graphical data characterize the
`
`samesolid state form or two different solid state forms. The skilled person would understand
`
`that a solid state form referred to herein as being characterized by graphical data “as shown
`
`in” a Figure would include any solid state form of the same chemical characterized by
`
`

`

`WO2013/078361
`
`PCT/US2012/066324
`
`graphical data substantially similar to the Figure except for such small variations, the
`
`potential occurrence of which is well knownto the skilled person.
`
`[0087]
`
`A solid state form may be referred to herein as being characterized by data
`
`selected from two or more different data groupings, for example, by a powder XRD pattern
`
`having a group of specific peaks; or by a powder XRD pattern as shownin a figure depicting
`
`a diffractogram, or by “a combination thereof” (or “combinationsthereof,” or “any
`
`combination thereof”), These expressions, e.g., “any combination thereof’ contemplate that
`
`the skilled person may characterize a crystal form using any combination ofthe recited
`
`characteristic analytical data. For example, the skilled person may characterize a crystal form
`
`using a group offour or five characteristic powder XRD peaks, and supplementthat
`
`characterization with one or more additional features observed in the powder X-ray
`
`diffractogram, e.g., an additional peak, a characteristic peak shape, a peak intensity, or even
`
`the absence of a peak at some position in the powder XRD pattern. Alternatively, the skilled
`
`person may in someinstances characterize a crystal form using a group offouror five
`
`characteristic powder XRD peaks and supplement that characterization with one or more
`
`additional features observed using another analytical method, for example, using one or more
`
`characteristic peaks in a solid state NMR spectrum, or in a Raman spectrum, or
`
`characteristics of the DSC thermogram ofthe crystal form that is being characterized.
`
`As used herein, unless stated otherwise, powder XRD peaks reported herein are
`[0088]
`measured using CuK, radiation, A = 1.54184 A.
`
`[0089]
`
`As used herein, unless indicated otherwise, the term "room temperature" or "RT"
`
`or “ambient temperature” refers to a temperature between about 20 °C and about 30 °C.
`
`Usually, room temperature ranges from about 20 °C to about 25 °C.
`
`[0090]
`
`As used herein, unless indicated otherwise, the term “overnight” refers to a period
`
`of between about 15 and about 20 hours, typically between about 16 to about 20 hours.
`
`[0091]
`
`As used herein, and unless stated otherwise, the term “anhydrous” in relation to
`
`crystalline Vilazodone or Vilazodone hydrochloride relates to a crystalline Vilazodone or
`
`Vilazodone hydrochloride which contains no more than 1% (w/w), more preferably no more
`
`than 0.5% (w/w) of either water or organic solvents as measured by TGA,or by KF.
`
`[0092]
`
`As used herein, and unless stated otherwise the term "solvate" refers to a crystal
`
`form that incorporates a solventin the crystal structure. When the solvent is water, the solvate
`
`

`

`WO2013/078361
`
`PCT/US2012/066324
`
`is often referred to as a "hydrate." The solvent in a solvate may bepresent in either a
`
`stoichiometric or in a non-stoichiometric amount.
`
`[0093]
`
`As used herein, Form IV relates to a crystalline form of Vilazodone HCL, as
`
`described in thePCT Publication No. WO2002102794.
`
`[0094]
`
`The present invention providessolid state forms of Vilazodonebase.
`
`[0095]
`
`In one embodiment, the present invention provides a Vilazodone methanolsolvate.
`
`[0096]
`
`The present invention also providesa crystalline Vilazodone, designated Form A.
`
`Form A can be characterized by data selected from: a powder XRD pattern with peaksat 5.2,
`
`
`7.7, 10.5, 14.8, and 24.7 + 0.2 degrees 20; a powder XRD pattern as shown in Figure 1; and
`
`any combinationsthereof.
`
`[0097]
`
`Alternatively, Form A can be characterized by a powder XRD pattern having peaks
`
`
`at 5.2, 7.7, 10.5, 14.8, and 24.7 + 0.2 degrees 20, and also having any one, two, three, four or
`
`
`five peaks selected from 16.1, 17.7, 18.6, 19.6, and 24.1 + 0.2 degrees 20.
`
`[0098]
`
`Form A can befurther characterized by a DSC thermogram as shownin Figure 2.
`
`[0099]
`
`Form A can be a methanol solvate. Form A can be a solvate containing methanol
`
`and water. According to some embodiments, Form A may contain from about 2.0% to about
`
`4.0% w/w water, for example about 2.4% w/w of water, as measured by KF; and from about
`
`4.0% to about 6.0% w/w of methanol, for example about 4.8% w/w of methanol, as measured
`
`by GC.
`
`[00100] The present invention also provides Vilazodone methyl isobutyl ketone solvate.
`
`[00101] The present invention also provides a crystalline Vilazodone, designated Form B.
`
`Form B can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`5.8, 7.3, 10.9, 18.6, and 20.9 + 0.2 degrees 20; a powder XRD pattern as shownin Figure 3;
`
`and any combinationsthereof.
`
`[00102] Alternatively, Form B can be characterized by a powder XRD pattern having peaks
`
`
`at 5.8, 7.3, 10.9, 18.6, and 20.9 + 0.2 degrees 20, and also having any one, two, three, four or
`
`
`five peaks selected from 13.8, 16.0, 17.3, 21.4, and 21.9 + 0.2 degrees 20.
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`[00103]
`
`Form B canbe further characterized by a DSC thermogram as shownin Figure4.
`
`[00104]
`
`Form B can be a methyl isobutyl ketone solvate. Form B can be a solvate
`
`containing methyl isobutyl ketone and from about 3.0% to about 4.0% w/w of water, for
`
`example, about 3.8% w/w of water, as measured by KF.
`
`[00105] The present invention further provides Vilazodone ethylene glycol solvate.
`
`[00106] The present invention also provides a form of Vilazodone, designated Form C.
`
`Form C can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`3.9, 9.6, 13.2, 19.7, and 24.0 + 0.2 degrees 20; a powder XRD pattern as shownin Figure 5;
`
`and any combinationsthereof.
`
`[00107] Alternatively, Form C can be characterized by a powder XRD pattern having peaks
`
`
`at 3.9, 9.6, 13.2, 19.7, and 24.0 + 0.2 degrees 20, and also having any one, two, three, four or
`
`
`five peaks selected from 15.1, 16.0, 20.9, 22.8 and 27.0 + 0.2 degrees 29.
`
`[00108]
`
`Form C can be further characterized by a DSC thermogram as shownin Figure6.
`
`[00109]
`
`Form C can be an ethylene glycol solvate. Form C can be a solvate containing
`
`ethylene glycol and from about 5.0% to about 7.0% w/w of water, for example, about 5.9%
`
`w/w of water, as measured by KF.
`
`[00110] The invention further provides a Vilazodone 1-propanolsolvate.
`
`[00111] The present invention also provides a crystalline Vilazodone, designated Form D.
`
`Form D can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`5.0, 6.8, 8.4, 20.0, and 29.1 + 0.2 degrees 20; a powder XRD pattern as shown in Figure 7;
`
`and any combinationsthereof.
`
`[00112] Alternatively, Form D can be characterized by a powder XRD pattern having peaks
`
`
`at 5.0, 6.8, 8.4, 20.0, and 29.1 + 0.2 degrees 20, and also having any one, two, three, four, or
`
`
`five peaks selected from 11.9, 14.4, 16.7, 18.0, and 20.7 + 0.2 degrees 20.
`
`[00113]
`
`Form D can be a 1-propanol solvate. Form D can be a solvate containing 1-
`
`propanol and water. For example, Form D may contain from about 15.0% to about 16.0%
`
`w/w of 1-propanol, for example about 15.4% w/w, as measured by GC.
`
`10
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`[00114]
`
`Form D can befurther characterized by a DSC thermogram as shownin Figure 8.
`
`[00115] The present invention also provides Vilazodoneethanolsolvate.
`
`[00116] The present invention also provides a crystalline Vilazodone, designated Form E.
`
`Form E can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`5.2, 20.3, 21.3, 22.5, 26.6, and 27.4 + 0.2 degrees 20; a powder XRD pattern as shown in
`
`Figure 9; and any combinationsthereof.
`
`[00117] Alternatively, Form E can be characterized by a powder XRD pattern having peaks
`
`
`at 5.2, 20.3, 21.3, 22.5, 26.6, and 27.4 + 0.2 degrees 20, and also having any one,two, three,
`
`
`or four peaks selected from 6.8, 8.5, 16.6, and 29.8 + 0.2 degrees 20.
`
`[00118]
`
`Form E can be further characterized by a DSC thermogram as shownin Figure 10.
`
`[00119]
`
`Form E can be an ethanol solvate. Form E can be a solvate containing from about
`
`3.0% to about 5.0% w/w of ethanol, for example about 3.6% w/w ofethanol, as measured by
`
`GC, and from about 4.0% to about 6.0% w/w of water, for example about 4.3% w/w of water,
`
`as measured by KF.
`
`[00120] The present invention further provides Vilazodone 1-butanolsolvate.
`
`[00121] The present invention also provides a crystalline Vilazodone, designated Form F.
`
`Form F can be characterized by data selected from: a powder XRDpattern having peaksat
`
`
`5.0, 6.8, 14.4, 22.2, and 22.6 + 0.2 degrees 20; a powder XRD pattern as shown in Figure 11;
`
`and any combinationsthereof.
`
`[00122] Alternatively, Form F can be characterized by a powder XRD pattern having peaks
`
`
`at 5.0, 6.8, 14.4, 22.2, and 22.6 + 0.2 degrees 20, and also having any one, two, three, four, or
`
`
`five peaks selected from 8.4, 12.1, 18.2, 19.5 and 20.9 + 0.2 degrees 20.
`
`
`
`[00123] FormFcan be further characterized by a DSC thermogram as shownin Figure 12.
`
`[00124]
`
`Form F can be a 1-butanol solvate. Form F can be a solvate containing from about
`
`17.0% to about 19.0% w/w of 1-butanol, for example, about 17.3% w/w of 1-butanol, as
`
`measured by GC, and from about 3.0% to about 5.0% w/w of water, for example, about 3.7%
`
`w/w of water, as measured by KF.
`
`11
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`[00125] The present invention also provides a crystalline Vilazodone, designated Form G.
`
`Form G can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`5.7, 7.3, 10.9, 13.8, and 24.0 + 0.2 degrees 20; a powder XRD pattern as shown in Figure 13;
`
`and any combinationsthereof.
`
`[00126]
`
`Form Gcanbe an anhydrous.
`
`[00127] Alternatively, Form G can be characterized by a powder XRD pattern having peaks
`
`
`at 5.7, 7.3, 10.9, 13.8, and 24.0 + 0.2 degrees 20, and also having any one, two, three, four, or
`
`
`five peaks selected from 13.3, 17.4, 18.5, 20.9 and 21.3 + 0.2 degrees 20.
`
`[00128] The present invention also provides a crystalline Vilazodone, designated Form H.
`
`Form H can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`5.7, 9.0, 10.0, 17.0, and 23.1 + 0.2 degrees 20; a powder XRD pattern as shown in Figure 14;
`
`and any combinationsthereof.
`
`[00129]
`
`Form H can be an anhydrous.
`
`[00130] Alternatively, Form H can be characterized by a powder XRD pattern having peaks
`
`
`at 5.7, 9.0, 10.0, 17.0, and 23.1 + 0.2 degrees 20, and also having any one, two, three, four, or
`
`
`five peaks selected from 7.3, 15.3, 15.7, 18.4, and 20.3 + 0.2 degrees 29.
`
`[00131] The present invention also provides a crystalline Vilazodone, designated Form I.
`
`Form I can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`5.5, 8.6, 17.7, 20.3, and 22.9 + 0.2 degrees 20; a powder XRD pattern as shown in Figure 15;
`
`and any combinationsthereof.
`
`[00132] Alternatively, Form I can be characterized by a powder XRDpattern having peaks
`
`
`at 5.5, 8.6, 17.7, 20.3, and 22.9 + 0.2 degrees 20, and also having any one, two, three, four, or
`
`
`five peaks selected from 7.2, 10.5, 12.7, 13.4, and 14.5 + 0.2 degrees 29.
`
`[00133]
`
`Form I can be an anhydrous.
`
`[00134] The present invention also provides a crystalline Vilazodone, designated Form E1.
`
`Form E1 can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`5.5, 6.8 and 8.3 degrees 20 + 0.2 degrees 20; a powder XRD pattern as shown in Figure 20;
`
`and any combinationsthereof.
`
`12
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`[00135]
`
`Form El maybe a hydrate, or a methanol solvate — hydrate. For example, Form El
`
`may contain from about 2.0% to about 4.0% w/w of water, for example about 2.6% w/w of
`
`water, as measured by KF, and from about 5.0% to about 7.0% w/w of ethanol, for example
`
`about 6.0% w/w ofethanol, as measured by GC.
`
`[00136] Alternatively, Form EI can be characterized by a powder XRD pattern having
`
`
`peaks at 5.5, 6.8 and 8.3 degrees 20 + 0.2 degrees 20, and also having any one, two or three
`
`
`peaks selected from 12.2, 13.5 and 17.0 degrees 20 + 0.2 degrees 29.
`
`[00137]
`
`Form El can be further characterized by a DSC thermogram as shownin Figure
`
`21.
`
`[00138]
`
`Form E]1 can be characterized by any combination of the above analytical data.
`
`[00139] The present invention also provides a crystalline Vilazodone, designated Form A1.
`
`Form A1 can be characterized by data selected from: a powder XRD pattern having peaks at
`
`
`5.6, 11.1, 22.6 and 25.1 degrees 20 + 0.2 degrees 20; a powder XRD pattern as shown in
`
`Figure 22; and any combinationsthereof.
`
`[00140]
`
`Form Al may bea hydrate, or a methanol solvate — hydrate. For example, Form
`
`Al may contain from about 3% to about 5% w/w of water, for example about 3.3% w/w of
`
`water, as measured by KF, and from about 1% to about 3% w/w of methanol, for example
`
`about 1.9% w/w of methanol, as measured by GC.
`
`[00141] Alternatively, Form AI can be characterized by a powder XRD pattern having
`
`
`peaks at 5.6, 11.1, 22.6 and 25.1 degrees 20 + 0.2 degrees 20, and also having any one, two,
`
`
`three, four, five or six peaks selected from 7.7, 14.4, 16.1, 18.8, 20.6 and 27.0 degrees 20 +
`
`0.2 degrees 20.
`
`[00142]
`
`Form A] can be further characterized by a DSC thermogram as shownin Figure
`
`23.
`
`[00143]
`
`Form A1 can be characterized by any combination of the above data.
`
`[00144] The present invention also provides a crystalline Vilazodone, designated Form K.
`
`Form K can be characterized by data selected from: a powder XRD pattern having peaksat
`
`13
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`
`7.0, 13.9, 16.9, 19.9, and 20.9 degrees 20 + 0.2 degrees 20; a powder XRD pattern as shown
`
`in Figure 62; and any combinationsthereof.
`
`[00145] Alternatively, Form K can be characterized by a powder XRD pattern having peaks
`
`
`at 7.0, 13.9, 16.9, 19.9, and 20.9 degrees 20 + 0.2 degrees 20, and also having any one or
`
`
`more peaksselected from 10.2, 15.7, 19.0, 22.3, and 26.3 degrees 20 + 0.2 degrees 20.
`
`[00146]
`
`Form K can be further characterized by a DSC thermogram as shownin Figure 63.
`
`[00147]
`
`Form K can be characterized by any combination of the above analytical data.
`
`[00148] The present invention also provides a crystalline Vilazodone, designated Form L.
`
`Form L can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`9.1, 12.9, 14.7, 15.2, and 22.9 degrees 20 + 0.2 degrees 20; a powder XRD pattern as shown
`
`in Figure 64; and any combinationsthereof.
`
`[00149] Alternatively, Form L can be characterized by a powder XRD pattern having peaks
`
`
`at 9.1, 12.9, 14.7, 15.2, and 22.9 degrees 20 + 0.2 degrees 20, and also having any one or
`
`
`more peaksselected from 5.3, 16.6, 17.2, 19.5, and 20.1 degrees 20 + 0.2 degrees 20.
`
`[00150]
`
`Form L can be further characterized by a DSC thermogram as shownin Figure 65.
`
`[00151]
`
`Form L can be characterized by any combination of the above analytical data.
`
`[00152] The present invention also provides a crystalline Vilazodone, designated Form M.
`
`Form M can be characterized by data selected from: a powder XRD pattern having peaksat
`
`
`5.4, 7.2, 8.6, 17.6 and 22.8 degrees 20 + 0.2 degrees 20; a powder XRD pattern as shown in
`
`Figure 66; and any combinationsthereof.
`
`[00153] Alternatively, Form M can be characterized by a powder XRD pattern having
`
`
`peaks at 5.4, 7.2, 8.6, 17.6 and 22.8 degrees 20 + 0.2 degrees 20, and also having any one or
`
`
`more peaksselected from 10.5, 10.8, 12.8, 14.4, and 15.1 degrees 20 + 0.2 degrees 20.
`
`[00154] The present invention also provides amorphous Vilazodone.
`
`[00155] The amorphous Vilazodone can be characterized by a powde