(12) Patent Application Publication (10) Pub. No.: US 2016/0346252 A1 PALLING Et Al
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US 2016.0346252A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0346252 A1 PALLING et al. (43) Pub. Date: Dec. 1, 2016 (54) NOVEL NITROMIDAZOLE Publication Classification FORMULATIONS AND USES THEREOF (51) Int. Cl. (71) Applicant: SYMBIOMIX THERAPEUTICS, A63L/464 (2006.01) LLC, Newark, NJ (US) A69/48 (2006.01) A 6LX 9/50 (2006.01) (72) Inventors: David PALLING, Glen Ridge, NJ (52) U.S. Cl. (US); Ronald S. VLADYKA, CPC ......... A61K 31/4164 (2013.01); A61K 9/5026 Hillsborough, NJ (US); Joseph (2013.01); A61K 9/5031 (2013.01); A61 K AMPREY, Potomac, MD (US) 9/485 (2013.01) (73) Assignee: SYMBIOMIX THERAPEUTICS, LLC, Newark, NJ (US) (57) ABSTRACT (21) Appl. No.: 15/170,572 (22) Filed: Jun. 1, 2016 Embodiments described herein are directed to novel phar maceutical compositions comprising a plurality of micro Related U.S. Application Data granules comprising nitroimidazole compounds, and uses of (60) Provisional application No. 62/169,369, filed on Jun. these pharmaceutical compositions in the treatment of bac 1, 2015. terial vaginosis. US 2016/0346252 A1 Dec. 1, 2016 NOVEL NITROMIDAZOLE ments, the nitroimidazole compound is selected from sec FORMULATIONS AND USES THEREOF nidazole, metronidazole, tinidazole, nimorazole, dimetrida Zole, 6-Amino PA824, ornidazole, megaZol, azanidazole, CROSS REFERENCE RELATED APPLICATIONS benZnidazole, pimonidazole, and combinations thereof. In Some embodiments, the nitroimidazole compound is sec 0001. This application claims the benefit of priority to nidazole. In some embodiments, the nitroimidazole com U.S. Provisional Application No. 62/169,369 entitled pound comprises at least about 70% of the core by weight. “Novel Nitroimidazole Formulations And Uses Thereof In some embodiments, the nitroimidazole compound com filed Jun. 1, 2015; the disclosure of which is incorporated by prises about 70% of the core by weight. In some embodi reference in its entirety. ments, the plurality of microgranules comprise about 1 gram to about 2 grams of the nitroimidazole compound. In some SUMMARY embodiments, the core further comprises at least one poly 0002 Embodiments herein are directed to pharmaceuti mer. In some embodiments, the polymer is selected from cal compositions comprising a plurality of microgranules, Avicel, Methocel, hydroxyl propyl cellulose, acacia, guar wherein the microgranules comprise a core and a coating: gum, povidone, lactose monohydrate, and any combination wherein the core comprises a nitroimidazole compound or thereof. In some embodiments, the core further comprises pharmaceutically acceptable salt thereof; and wherein the Avicel and Methocel. In some embodiments, the core further coating Surrounds the core. In some embodiments, the comprises Avicel pH101 and Methocel AV 15LV. In some nitroimidazole compound is selected from secnidazole, met embodiments, the polymer comprises about 30% of the core ronidazole, tinidazole, nimorazole, dimetridazole, 6-Amino by weight. In some embodiments, the coating comprises a PA824, ornidazole, megaZol, azanidazole, benznidazole, polymer. In some embodiments, the polymer is selected pimonidazole, and combinations thereof. In some embodi from Eudagrit(R), ethyl cellulose, methocel, glyceryl behen ments, the nitroimidazole compound is secnidazole. In some ate, and any combination thereof. In some embodiments, the embodiments, the nitroimidazole compound comprises at polymer is Eudagrit NE30D. In some embodiments, the least about 70% of the core by weight. In some embodi coating further comprises a polyether polymer. In some ments, the nitroimidazole compound comprises about 70% embodiments, the polyether polymer is selected from poly of the core by weight. In some embodiments, the plurality of ethylene glycol, acetyl tributyl citrate, triethyl citrate, dibu microgranules comprise about 1 gram to about 2 grams of tyl phthalate, dibutyl sebacate, gelatin, propelyne glycol, the nitroimidazole compound. In some embodiments, the triacetin, and any combination thereof. In some embodi plurality of microgranules comprise a therapeutically effec ments, the polyether polymer is PEG 4000. In some embodi tive amount of the nitroimidazole compound. In some ments, the coating further comprises talc. In some embodi embodiments, the core further comprises at least one poly ments, the coating comprises about 13% of the composition mer. In some embodiments, the polymer is selected from by weight. Some embodiments further comprise talc. In Avicel(R), Methocel(R), hydroxyl propyl cellulose, acacia, Some embodiments, the core comprises a spheronized guar gum, povidone, lactose monohydrate, and any combi microgranule. In some embodiments, the core further com nation thereof. In some embodiments, the core further prises a binder. comprises Avicel and Methocel. In some embodiments, the core further comprises Avicel pH101 and Methocel AV 15LV. DETAILED DESCRIPTION In some embodiments, the polymer comprises about 30% of 0004 Embodiments described herein are directed to the core by weight. In some embodiments, the coating novel pharmaceutical compositions comprising a plurality comprises a polymer. In some embodiments, the polymer is of microgranules; wherein the microgranules comprise a selected from Eudagrit(R), ethyl cellulose, methocel, glyceryl core and a coating; wherein the core comprises a nitroimi behenate, and any combination thereof. In some embodi dazole compound or pharmaceutically acceptable salt ments, the polymer is Eudagrit NE30D. In some embodi thereof, and wherein the coating Surrounds the core. In some ments, the coating further comprises a polyether polymer. In embodiments, the pharmaceutical compositions described Some embodiments, the polyether polymer is selected from herein are designed for oral administration. polyethylene glycol, acetyl tributyl citrate, triethyl citrate, 0005. Current nitroimidazole drugs such as secnidazole dibutyl phthalate, dibutyl sebacate, gelatin, propelyne gly are effective in the treatment of several conditions including col, triacetin, and any combination thereof. In some embodi bacterial vaginosis. However, the dosages required for treat ments, the polyether polymer is PEG 4000. In some embodi ment and the current formulations mean that very large ments, the coating further comprises talc. In some amount of the drug must be taken by a patient which raises embodiments, the coating comprises about 13% of the the risk of non-compliance by patients and the exclusion of composition by weight. Some embodiments further com certain patients not able to ingest the amount of drug prise talc. In some embodiments, the core comprises a required. Applicant has developed novel pharmaceutical spheronized microgranule. In some embodiments, the core compositions comprising microgranules that allow for thera further comprises a binder. peutic dosing in Smaller unit doses thus addressing the 0003. Some embodiments are directed to methods of problems caused by the conventional drug formulations and treating bacterial vaginosis in patient comprising adminis high doses required for therapeutic effectiveness. tering to the patient a pharmaceutical composition compris 0006 Before the present formulations and methods are ing a plurality of microgranules, wherein the microgranules described, it is to be understood that this invention is not comprise a core and a coating; wherein the core comprises limited to the particular processes, compounds, or method therapeutically effective amount of a nitroimidazole com ologies described, as these may vary. It is also to be pound or pharmaceutically acceptable salt thereof, and understood that the terminology used in the description is for wherein the coating Surrounds the core. In some embodi the purpose of describing the particular versions or embodi US 2016/0346252 A1 Dec. 1, 2016 ments only, and is not intended to limit the scope of the may refer to the amount of an active agent or pharmaceutical present invention. Unless defined otherwise, all technical compound or composition that elicits a clinical, biological or and Scientific terms used herein have the same meanings as medicinal response in a tissue, system, animal, individual or commonly understood by one of ordinary skill in the art. human that is being sought by a researcher, veterinarian, Although any methods and materials similar or equivalent to medical doctor or other clinical professional. A clinical, those described herein can be used in the practice or testing biological or medical response may include, for example, of embodiments of the present invention, the preferred one or more of the following: (1) preventing a disease, methods, devices, and materials are now described. All condition or disorder in an individual that may be predis publications mentioned herein are incorporated by reference posed to the disease, condition or disorder but does not yet in their entirety. experience or display pathology or symptoms of the disease, 0007. In each of the embodiments disclosed herein, the condition or disorder, (2) inhibiting a disease, condition or compounds and methods may be utilized with or on a subject disorder in an individual that is experiencing or displaying in need of such treatment, which may also be referred to as the pathology or symptoms of the disease, condition or “in need thereof. As used herein, the phrase “in need disorder or arresting further development of the pathology thereof means that the subject has been identified as having and/or symptoms of the disease, condition or disorder, and