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(12) Patent Application Publication (10) Pub. No.: US 2012/0202780 A1 Gavin Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2012/0202780 A1 Gavin Et Al US 20120202780A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0202780 A1 Gavin et al. (43) Pub. Date: Aug. 9, 2012 (54) CARRIER COMPOSITION Publication Classification (76) Inventors: Paul David Gavin, Chadstone (51) Int. Cl. (AU); Mahmoud El-Tamimy, A6II 47/24 (2006.01) Meadow Heights (AU); Jeremy A6II 3/196 (2006.01) James Cottrell, Caulfield South A6IP5/00 (2006.01) (AU); Giacinto Gaetano, South A 6LX 3/573 (2006.01) Melbourne (AU); Nicholas John A6IP 23/00 (2006.01) Kennedy, Boronia (AU) A6IP 29/00 (2006.01) A6II 3/167 (2006.01) (21) Appl. No.: 13/501,494 A63L/407 (2006.01) (22) PCT Fled: Dec. 22, 2010 (52) U.S. Cl. ......... 514/180: 514/785: 514/788: 514/772: 514/626; 514/567; 514/413: 514/179 (86) PCT NO.: S371 (c)(1), (57) ABSTRACT (2), (4) Date: Apr. 12, 2012 A carrier composition of the present invention comprises a phosphate compound of an electron transfer agent and a rela Related U.S. Application Data tively high concentration of a polar protic solvent. A biologi (60) Provisional application No. 61/289,507, filed on Dec. cally active compound may be formulated with a carrier com 23, 2009. position of the present invention to provide a formulation. Patent Application Publication Aug. 9, 2012 Sheet 1 of 5 US 2012/0202780 A1 - - if solvent E. -ie-20% solvent 3. ". S. .t E FGURE 1 Patent Application Publication Aug. 9, 2012 Sheet 2 of 5 US 2012/0202780 A1 -H 10 LC2 s -C- 20 ulcm2 . - a 30 ulcm2 t E re FIGURE 2A HO licm2 80i -o- 20 ul/cm2 'i -A-30 ul/cm2 140 EO 10 8 8 4) O O FIGURE 2B Patent Application Publication Aug. 9, 2012 Sheet 3 of 5 US 2012/0202780 A1 16C.. O 1. 1. 8, O.O. 6.O. 4. 2O. O. O 1% (8:2), 5% Lido, 80%. 1% (2:1), 1 % Lido., 30 % EtO-, 3-, HPC G EtOH, 1 %, CP 934 FIGURE 3 Patent Application Publication Aug. 9, 2012 Sheet 4 of 5 US 2012/0202780 A1 2O,OO 18.00 16, OO A.OO 12.OO OOO 8.00 6.OO 4.00 2.OO O.OO Woltare PM-02. Dico HS TPM-02A Diclo LS Treatment FIGURE 4 Patent Application Publication Aug. 9, 2012 Sheet 5 of 5 US 2012/0202780 A1 Keterolac deposition in rat abdominal skir 5 11. 5 . FIGURE 5 US 2012/0202780 A1 Aug. 9, 2012 CARRIER COMPOSITION the electron transfer agent is a hydroxy chroman, preferably a tocol such as tocopherol or tocotrienol. TECHNICAL FIELD 0014 Phosphate compounds of tocopherol may be 0001. The present invention relates to carrier composi selected from the group consisting of mono-(tocopheryl) tions for delivery of biologically active compounds. phosphate, mono-(tocopheryl) phosphate monosodium salt, mono-(tocopheryl) phosphate monopotassium salt, mono BACKGROUND (tocopheryl) phosphate disodium salt, mono-(tocopheryl) 0002. In this specification where a document, act or item phosphate dipotassium salt, di-(tocopheryl) phosphate, di of knowledge is referred to or discussed, this reference or (tocopheryl) phosphate monosodium salt, di-(tocopheryl) discussion is not an admission that the document, actor item phosphate monopotassium salt, or a mixture thereof. of knowledge or any combination thereof was at the priority 0015. When the carrier composition comprises a mixture date, publicly available, known to the public, part of common of a mono-(tocopheryl) phosphate to a di-(tocopheryl) phos general knowledge; or known to be relevant to an attempt to phate, the ratio is preferably at least 2:1, more preferably solve any problem with which this specification is concerned. within the range of about 4:1 to about 1:4, most preferably 0003 Drug delivery is the method or process of adminis tering a pharmaceutical compound to achieve a therapeutic within the range of about 6:4 to about 8:2. In preferred effect in humans and animals. embodiments the ratio is about 6:4 or about 8:2. 0004 Drug delivery technologies have been developed to 0016. The carrier composition comprises a phosphate improve bioavailability, safety, duration, onset or release, of compound of an electron transfer agent in an amount within the pharmaceutical compound. the range of preferably about 0.01% w/w to about 20% w/w, 0005. When developing drug delivery technologies, prob more preferably about 0.01% w/w to about 10% w/w, most lems likely to be encountered include compatibility of the preferably about 0.01% w/w to about 5% w/w or about 0.01% drug delivery system and the pharmaceutical compound, wfw to about 1% w/w of the total concentration of the carrier maintaining an adequate and effective duration, potential for composition. In one embodiment the carrier composition side effects, and meeting patient convenience and compli ance. As a consequence, many drug delivery technologies fall comprises a phosphate compound of an electron transfer short of desired improvements and requirements. agent in an amount within the range of about 0.01% w/w to 0006. Accordingly, there is still a need for alternate drug about 2% w/w, preferably about 0.05% w/w, about 0.1% w/w delivery systems which effectively deliver drugs. or about 1% w/w. In a further embodiment, a range of about 5% w/w to about 10% w/w or about 10% w/w to about 15% SUMMARY w/w may be used. 0007. It has surprisingly been found that a carrier compo 0017. In a second aspect of the invention there is provided sition comprising a phosphate compound of an electron trans a formulation comprising the carrier composition and a bio fer agent and a relatively high concentration of a polar protic logically active compound. Solvent can improve the delivery of a biological active com 0018. There is also provided a process for the preparation pound. of the formulation which comprises the step of adding a 0008 According to a first aspect of the invention there is biologically active compound to the carrier composition. provided a carrier composition for delivery of a biologically 0019. In one embodiment, the biologically active com active compound comprising a phosphate compound of an pound is lipophilic having a logP value within the range of electron transfer agent and a polar protic solvent, wherein the about 1 to about 5. The biologically active compound also polar protic solvent concentration is greater than 50% w/w of preferably has a relatively low molecular mass and a rela the total concentration of the carrier composition. tively low melting point. 0009. There is also provided use of a phosphate compound of an electron transfer agent and a polar protic solvent in the 0020. A biologically active compound may be present in manufacture of the carrier composition. an amount of up to about 30% w/w of the total concentration 0010. There is further provided a process for the prepara of the carrier composition. tion of the carrier composition which comprises the step of 0021. In a third aspect of the invention there is provided combining a phosphate compound of an electron transfer use of the carrier composition to improve the delivery of a agent and a polar protic solvent until complete homogenisa biologically active compound formulated with the carrier tion is achieved. composition. 0011. The polar protic solvent concentration is within the 0022. There is also provided use of the carrier composition range of preferably about 60% w/w to about 90% w/w, more to alter A.D.M.E. properties of a biologically active com preferably about 65% w/w to about 85% w/w, most prefer pound. ably about 70% w/w to about 80% w/w. In some circum stances, a suitable range may be about 50% w/w to about 60% 0023 There is further provided use of the carrier compo w/w, about 60% w/w to about 70% w/w or about 80% w/w to sition to improve the bioavailability of a biologically active about 90% w/w. compound in a Subject. 0012. In one embodiment the polar protic solvent is an 0024. In a fourth aspect of the invention there is provided acyclic alcohol. A C-C acyclic alcohol is preferred, and a method for treating a subject for a pathological condition ethanol and propanol are most preferred. which comprises administering an effective amount of a bio 0013 The electron transfer agent may be an antioxidant or logically active compound in the carrier composition. The a derivatised compound thereof. In a preferred embodiment pathological conditions include those that can be treated by US 2012/0202780 A1 Aug. 9, 2012 the biologically active compound formulated with the carrier composition. (I) DETAILED DESCRIPTION 0025. A carrier composition of the present invention com prises a phosphate compound of an electron transfer agent and a relatively high concentration of a polar protic solvent. A biologically active compound may be formulated with a car rier composition of the present invention to provide a formu lation. 0026. In this specification, except where the context R R2 R requires otherwise, the words “comprise”, “comprises, and C-tocopherol CH CH CH “comprising mean “include”, “includes”, and “including C-tocotrienol CH CH CH respectively, i.e. when the invention is described or defined as B-tocopherol CH H CH B-tocotrienol CH H CH comprising specified features, various embodiments of the Y-tocopherol H CH CH same invention may also include additional features. Y-tocotrienol H CH CH 8-tocopherol H H CH Phosphate Compound of an Electron Transfer Agent 8-tocotrienol H H CH 0027.
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