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(US). DIONNE, Dr. Raymond A.; 208 New (74) Agent ) ( (51) International Patent Classification: olina 27614 (US). DIONNE, Dr. Raymond A.; 208 New A61K9/00 (2006.01) A61F 13/00 (2006.01) Street, New Bern, North Carolina 28560 (US). A61L 24/00 (2006.01) A 6I K 9/70 (2006.01) (74) Agent: JOHNSTON, Michael; Taylor English Duma LLP, A61P23/02 (2006.01) A61L 15/44 (2006.01) 1600 Parkwood Circle, Suite 200, Atlanta, Georgia 30339 A61L 15/00 (2006.01) (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US20 19/048846 kind of national protection av ailable) . AE, AG, AL, AM, (22) International Filing Date: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 29 August 2019 (29.08.2019) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (25) Filing Language: English HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (26) Publication Language: English KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (30) Priority Data: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 62/725,694 31 August 2018 (3 1.08.2018) US SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/893,413 29 August 2019 (29.08.2019) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: RILENTO PHARMA, LLC [US/US]; 2301 (84) Designated States (unless otherwise indicated, for every Stonehenge Drive, Suite 117, Raleigh, North Carolina kind of regional protection av ailable) . ARIPO (BW, GH, 27615 (US). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (72) Inventors: NESHAT, Kevin; 300 Carpathian Way, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, Raleigh, North Carolina 27615 (US). DAUNCH, William TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Andrew; 110 Parkmeadow Drive, Cary, North Carolina EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 275 19 (US). PARKER, Anthony A.; 10 Columbine Cir¬ MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, cle, Newtown, Pennsylvania 18940 (US). HANNA, Mark Franklin; 13 13 Shining Water Lane, Raleigh, North Car¬ (54) Title: PHARMACEUTICAL FORMULATION AND SYSTEM AND METHOD FOR DELIVERY FIG. (57) Abstract: A sustained release pharmaceutical formulation for pain management comprises an active ingredient, and a water-mis¬ cible and hygroscopic network-forming material, the active ingredient being dispersed within the water-miscible and hygroscopic net¬ work-forming material. The pharmaceutical may comprise a hydrophobic component, wherein the active ingredient dispersed within the water-miscible and hygroscopic network-forming material are together dispersed in hydrophobic component. Optionally, the phar¬ maceutical formulation may be combined with a reinforcing member for providing a system for sustained release of the pharmaceutical formulation for pain management. [Continued on next page] ||| ||||| ||||| ||||| |||| 11| ||| ||||| ||||| ||||| ||||| ||||| |||| limn nil nil nil PHARMACEUTICAL FORMULATION AND SYSTEM AND METHOD FOR DELIVERY Cross-References This application is related t o U.S. provisional application No. 62/725,694, filed August 31, 2018, and U.S. provisional application No. 62/893,413, filed August 29, 2019. The contents of the provisional applications are incorporated herein by reference in their entirety, and the benefit of the filing dates of the provisional applications are hereby claimed for all purposes that are legally served by such claim for the benefit of the filing dates. Background A pharmaceutical formulation is described and, more particularly, a sustained release pharmaceutical formulation and a system and method for delivery of the pharmaceutical formulation for use, for example, for pain management in wounds such as dental extractions. There is currently no sustained delivery system commercially available for the specific indication of post-surgical pain after dental extractions. Ideally, such a product would require minimal preparation and preferably no preparation by the clinician, it would be easily placed into the tooth extraction socket or wound cavity by a clinician, it would have rheological properties that allow the formulation to be molded t o fill the extraction socket or wound void, it would preferably remain adhered and resist erosion throughout the treatment duration, it would have no adverse interactions with blood and would preferably function as a hemostat, it would have no local (acute or long-term) tissue or nerve toxicity, it would preferably be comprised of biocompatible ingredients, it would deliver pain medication both acutely after surgery and during healing while preferably addressing acute and sub-acute pain without delaying or adversely affecting wound healing, and it would preferably enhance wound healing. Products that are current benchmarks for rheological performance in dental surgery and tooth extraction applications include SU RGIFOAM ® Absorbable Gelatin Sponge and SU RGIFOAM ® Absorbable Gelatin Powder, each being examples of sterile porcine gelatin absorbable sponges or powders intended for hemostatic use by applying t o a bleeding surface ("Surgifoam"). GELFOAM ® Dental Sponges (absorbable gelatin sponge, USP) is a medical device also intended for application t o bleeding surfaces as a hemostatic. It is a water-insoluble, off-white, nonelastic, porous, pliable product prepared from purified pork skin gelatin USP granules and water for injection, and is able t o absorb and hold within its interstices many times its weight of blood and other fluids. Gelfoam ® absorbable gelatin powder (absorbable gelatin powder from absorbable gelatin sponge, USP) is a fine, dry, heat-sterilized light powder prepared by milling absorbable gelatin sponge ("Gelfoam"). Soluble collagen powders are another option. However, compared t o Surgifoam and Gelfoam, soluble collagen powder exhibits a slower rate of gelation since its rate of network entanglement leads t o slower achievement of solidification and final equilibrium properties. Surgifoam and Gelfoam also have a significantly higher rate of water adsorption while simultaneously retaining their solid character; a high overall capacity for water adsorption; and higher overall compliance with negligible elasticity at equal water levels in their final equilibrium state. Commercial collagens generally lead t o lower-compliance, rubbery networks. Presently, the pharmaceutical industry is focusing on the development of sustained release formulations designed t o release a drug at a predetermined rate and t o maintain a constant drug level for a specific period of time with minimal side effects. The basic rationale behind a sustained release drug delivery system is t o optimize the biopharmaceutical, pharmacokinetic and pharmacodynamics properties of a drug in such a way that the utility of the drug is maximized, its side-effects are reduced, and the disease management goals are achieved. There are several advantages of sustained release drug delivery over conventional dosage forms including improved patient compliance due t o less frequent drug administration, reduction of fluctuation in steady-state drug levels, maximum utilization of the drug, increased safety margins of potent drugs, and reduction in healthcare costs through improved therapy and shorter treatment periods. One of the basic goals of sustained release is t o provide a promising way t o decrease the side effects of a drug, first by preventing the fluctuation of the therapeutic concentration of the drug in the body, and secondly by reducing the frequency of dose administration t o increase the probability of patient compliance. According t o the Centers for Disease Control and Prevention, drug overdose deaths, including those involving opioids, continue t o increase in the United States. Deaths from drug overdose are up among both men and women, among all races, and among adults of nearly all ages. Two out of three drug overdose deaths involve an opioid. Opioids are substances that work in the nervous system of the body or in specific receptors in the brain t o reduce the intensity of pain. Overdose deaths from opioids, including prescription opioids, heroin, and synthetic opioids like fentanyl have increased almost six times since 1999. In 2017, drug overdoses of all types averaged 21.7 per 100,000 with opioids alone killing more than 47,000 people, and with opioids representing 67.8% of all drug overdose deaths. According t o the NIH HEAL Initiative (Helping t o End Addiction Long-term m ), more than 25 million Americans suffer from daily chronic pain. New treatment options for pain are needed t o reduce the number of people exposed t o the risks of opioids. Through the HEAL Initiative, NIH is supporting research to understand how chronic pain develops, making patients susceptible t o risks associated with opioid use. HEAL is developing a data sharing collaborative, new biomarkers for pain, and a clinical trials network for testing new pain therapies. Research efforts are also focusing on treatments for opioid misuse and addiction. According to the American Dental Association's official policies and statements on substance use disorders including the opioid crisis, specifically the Statement on the Use of Opioids in the Treatment of Dental Pain, dentists should follow and continually review Centers for Disease Control and state licensing board recommendations for safe opioid prescribing, dentists should consider treatment options that utilize best practices to prevent exacerbation of or relapse of opioid misuse, Dentists should consider nonsteroidal anti-inflammatory analgesics as the first-line therapy for acute pain management, and dentists should recognize multimodal pain strategies for management for acute postoperative pain as a means for sparing the need for opioid analgesics. U.S. Patent Nos. 8,253,569 and 9,943,466 and U.S. Patent Application Pub. No. 2018/0169080 describe sustained release formulations for dental applications. The contents of U.S. Patent Nos.
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