US 12,324,858 B2
Pharmaceutical formulation and system and method for delivery
Khashayar Kevin Neshat, Raleigh, NC (US); William Andrew Daunch, Cary, NC (US); Anthony A. Parker, Newtown, PA (US); Mark Franklin Hanna, Raleigh, NC (US); and Raymond A. Dionne, New Bern, NC (US)
Assigned to Rilento Pharma, LLC, Raleigh, NC (US)
Filed by Rilento Pharma, LLC, Raleigh, NC (US)
Filed on Aug. 29, 2019, as Appl. No. 16/555,669.
Claims priority of provisional application 62/893,413, filed on Aug. 29, 2019.
Claims priority of provisional application 62/725,694, filed on Aug. 31, 2018.
Prior Publication US 2020/0069595 A1, Mar. 5, 2020
Int. Cl. A61K 9/50 (2006.01); A61K 31/445 (2006.01)
CPC A61K 9/5031 (2013.01) [A61K 9/5052 (2013.01); A61K 9/5089 (2013.01); A61K 31/445 (2013.01)] 10 Claims
 
1. A non-hydrated compliant composite for sustained release of a pharmaceutical formulation for pain management following deployment in vivo, the composite comprising:
4% to 15% by weight of particulates of free bupivacaine;
5% to 25% by weight of particulates of gelatin having the capacity to become plasticized in vivo by body fluids and to undergo gelation over time to yield a macroscopic macromolecular chain-entangled gelled network;
16% to 26% by weight of caprylic triglyceride forming a hydrophobic fluid continuous phase medium, wherein the particulates of bupivacaine and the particulates of gelatin are co-dispersed within the hydrophobic fluid continuous phase medium to form a dispersion, such that the dispersed particulates of bupivacaine and gelatin are discrete and the dispersed particulates of gelatin are neither plasticized nor gelled by the hydrophobic fluid continuous phase medium; and
3% to 27% by weight of a water-soluble and bioresorbable fibrous reinforcing member comprising a cellulose hemostatic material having interstitial spaces capable of being impregnated by the dispersion for imparting mechanical reinforcement to the dispersion,
wherein the dispersion is impregnated into the interstitial spaces of the reinforcing component to form the non-hydrated compliant composite, and
wherein the non-hydrated compliant composite delivers at least 50 mg to 100 mg of the bupivacaine per cc of the composite and resists cohesive failure during handling and resists swelling and erosion for a period of time following deployment in vivo while simultaneously allowing uniform oral body fluid ingress for gelation of the network-forming material and the sustained release of the bupivacaine.