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WO 2015/052183 Al 16 April 2015 (16.04.2015) P O P C T

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WO 2015/052183 Al 16 April 2015 (16.04.2015) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/052183 Al 16 April 2015 (16.04.2015) P O P C T (51) International Patent Classification: (74) Agents: WELLS, Andrew et al; HGF Limited, 4th Floor, A61K 9/00 (2006.01) A61K 47/10 (2006.01) Merchant Exchange, 17-19 Whitworth Street West, A61K 9/70 (2006.01) A61K 31/445 (2006.01) Manchester M l 5WG (GB). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/EP2014/071437 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) Date: International Filing BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 7 October 2014 (07. 10.2014) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (30) Priority Data: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 13 17718.3 7 October 201 3 (07. 10.2013) GB 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. (71) Applicant: BUZZZ PHARMACEUTICALS LIMITED [IE/IE]; 15 Main Street, Raheny, Dublin, 5 (IE). (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (72) Inventors: JONES, Chris; An-Ex Analytical Services GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, Ltd., 14/16 CBTC2, Capital Business Park, Cardiff CF3 TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, 2PX (GB). GREEN, Darren; An-Ex Analytical Services TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, Ltd., 14/16 CBTC2, Capital Business Park, Cardiff CF3 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, 2PX (GB). LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, [Continued on nextpage] (54) Title: NOVEL FORMULATION 7.0 + 6.0 5.0 + 4.0 + 3.0 + 2.0 + 1.0 + -5% Lidocaine, Versatis (b/n : 346D01) 0.0 12 16 20 24 Time (h) Figure 13 (57) Abstract: The present invention relates to a transdermal patch comprising a pharmaceutical formulation, the formulation com prising ropivacaine or an opioid, a pharmaceutically-acceptable adhesive and optionally one or more excipients selected from the group consisting of carrier oils, [Continued on nextpage] WO 2015/052183 Al llll II II 11III II SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Published: GW, KM, ML, MR, NE, SN, TD, TG). _ , . with international search report (Art. 21(3)) Declarations under Rule 4.17: — of inventorship (Rule 4.17(iv)) penetration enhancers and hydrophilic materials. The present invention also relates to methods of preparation of such a pharma¬ ceutical formulation, as well as the use of such a transdermal patch in the treatment of pain (e.g. nociceptive and/or neuropathic pain). NOVEL FORMULATION FIELD OF THE INVENTION [0001] The present invention relates to a novel formulation. More specifically, the present invention relates to a novel anaesthetic or analgesic formulation suitable for transdermal administration. Such formulations are suitable for the topical treatment of neuropathic and/or nociceptive pain. The present invention also relates to processes for the preparation of the formulations defined herein, as well as to the use of these formulations for the topical treatment of neuropathic and/or nociceptive pain. BACKGROUND OF THE INVENTION [0002] Nociceptive pain is pain generated from nociceptors responding to stimuli by sending nerve signals to the spinal cord and brain. Such signals may be indicative of tissue irritation, impending injury, or actual injury, and are often characterized as aching and/or direct pains. Examples of conditions associated with nociceptive pain include bone fractures, burns, bumps, bruises, inflammation (from an infection or arthritic disorder), arthralgia, general myalgia and more specific myalgia caused by symptoms categorized generally as amplified musculoskeletal pain (AMP) syndrome. [0003] Neuropathic pain is pain caused by damage or disease that affects the somatosensory system. Neuropathic pain is the result of an injury or malfunction in the peripheral or central nervous system. The pain is often triggered by an injury, but it is not necessary for such an injury to involve actual damage to the central nervous system. Nerves can be infiltrated or compressed by tumours, strangulated by scar tissue, or inflamed by infection. The pain is typically characterized by burning, lancinating, coldness or so-called pins-and-needles-type sensations. Persistent allodynia - pain resulting from a non-painful stimulus such as a light touch - is also a common characteristic of neuropathic pain. The pain itself may have continuous and/or episodic (paroxysmal) components, the having electric shock-like qualities. The pain may persist for months or years beyond the apparent healing of any damaged tissue. In these scenarios, such pain signals no longer represent an alarm about ongoing or impending injury, rather it is the alarm system itself that is malfunctioning. Common causes of painful peripheral neuropathies are herpes zoster, infection, HIV-related neuropathies, nutritional deficiencies, toxins, remote manifestations of malignancies, immune mediated disorders and physical trauma to a nerve trunk. Neuropathic pain is also common in cases of cancer, either as a direct result of a cancer on peripheral nerves (for example through compression by a tumour), or as a side effect of chemotherapy radiation, injury or surgery. [0004] In certain conditions, the pain may be caused by a complex mixture of nociceptive and neuropathic factors. For example, myofascial pain is understood to result from nociceptive input from muscles. It is, however, plausible that such abnormal muscle activity is itself the result of neuropathic conditions. [0005] In both neuropathic and nociceptive disease types, neurons become unusually sensitive and develop spontaneous activity, abnormal excitability, and a heightened sensitivity to chemical, thermal and mechanical stimuli. This phenomenon is known as "peripheral sensitization". Localized delivery of anaesthetic can afford a method of desensitizing the aberrant stimuli. [0006] Lidocaine (often referred to as lignocaine) is widely used as a local anaesthetic, and is commercially available in both an injectable form and as a transdermal patch. When compared with a systemic dose, transdermal delivery of local anaesthetics provides prolonged anaesthesia at the target site for pain suppression, and involves reduced plasma levels, hence a reduced potential toxicity. [0007] However, in spite of the widespread use of lignocaine transdermal patches, there remains a need for improved transdermal anaesthetic formulations. [0008] In addition, there remains a need for improved analgesic transdermal patch formulations to provide analgesia, in particular improved patches for the delivery of opioid analgesics. [0009] There is also a need for transdermal formulations having good skin penetration properties. Moreover, there is a need for transdermal formulations of anaesthetic or analgesic agents that exhibit improved drug potency and having a longer duration of action for reducing the occurrence of breakthrough pain. [0010] Aspects of the invention were devised with the foregoing in mind. SUMMARY OF THE INVENTION [0011] The present invention provides a novel pharmaceutical formulation suitable for topical application for the treatment of pain, for example nociceptive and/or neuropathic pain. [0012] Thus, according to a first aspect of the invention, there is provided a transdermal patch comprising a pharmaceutical formulation, said formulation comprising ropivacaine or an opioid and a pharmaceutically-acceptable adhesive, and wherein said formulation has an in vitro permeation rate greater than 1.8 µg cm 2 h 1 . [0013] In another aspect, the present invention provides a transdermal patch comprising a pharmaceutical formulation, said formulation comprising: (i) ropivacaine or an opioid, (ii) a pharmaceutically-acceptable adhesive, and optionally (iii) one or more of either a penetration enhancer, a hydrophilic material, and a carrier oil having a ropivacaine or an opioid solubility of greater than or equal to 1.5% (w/w). [0014] In another aspect, the present invention provides a pharmaceutical formulation suitable for inclusion into a transdermal patch as herein defined, said formulation comprising ropivacaine or an opioid and a pharmaceutically-acceptable adhesive, and wherein said formulation has an in vitro human skin permeation rate greater than 1.8 µg cm 2 h 1 . [0015] In another aspect, the present invention provides a pharmaceutical formulation comprising: (i) ropivacaine or an opioid, (ii) a pharmaceutically-acceptable adhesive, and optionally (iii) one or more of either a penetration enhancer, a hydrophilic material, and a carrier oil having a ropivacaine or an opioid solubility of greater than or equal to 1.5% (w/w). wherein said formulation is suitable for inclusion into a transdermal patch as herein defined. [0016] In another aspect, the present invention provides a pharmaceutical formulation or transdermal patch as herein defined for use as a medicament. [0017] In another aspect, the present invention provides a pharmaceutical formulation or transdermal patch as herein
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