US-12622903-B2 - Drug products for intranasal administration and uses thereof

US12622903B2US 12622903 B2US12622903 B2US 12622903B2US-12622903-B2

Abstract

Provided herein are drug products adapted for nasal delivery comprising a device and a pharmaceutical composition comprising an opioid receptor antagonist, wherein the claimed invention provides a unit dose of an aqueous pharmaceutical solution, or aqueous pharmaceutical composition, housed in a device configured for intranasal administration to a patient, wherein the aqueous pharmaceutical solution consists of, or the aqueous pharmaceutical composition consists essentially of: (i) naloxone hydrochloride in an amount of about 9% by weight based on the total weight of the aqueous pharmaceutical solution; (ii) glycerin in an amount of about 1.4% by weight based on the total weight of the aqueous pharmaceutical solution; (iii) a citrate buffer system adjusted by hydrochloric acid and/or sodium hydroxide; and (iv) United States Pharmacopeia (USP)-grade Purified Water; wherein the pH of the aqueous pharmaceutical solution is from about 3.5 to about 4.7; and wherein the hydrochloric acid and the sodium hydroxide may each be independently present in the aqueous pharmaceutical solution, as required, to achieve the pH from about 3.5 to about 4.7.

Inventors

Gregory G. Plucinski
Adrian T. Raiche
Kristi R. Sims

Assignees

SUMMIT BIOSCIENCES INC.

Dates

Publication Date: 20260512
Application Date: 20240312

Claims (7)

1 . A unit dose of an aqueous pharmaceutical solution housed in a device configured for intranasal administration to a patient, wherein the aqueous pharmaceutical solution consists of: (i) naloxone hydrochloride in an amount of about 9% by weight based on the total weight of the aqueous pharmaceutical solution; (ii) glycerin in an amount of about 1.4% by weight based on the total weight of the aqueous pharmaceutical solution; (iii) a citrate buffer system adjusted by hydrochloric acid and/or sodium hydroxide; and (iv) United States Pharmacopeia (USP)-grade Purified Water; wherein the pH of the aqueous pharmaceutical solution is from about 3.5 to about 4.7; and wherein the hydrochloric acid and the sodium hydroxide may each be independently present in the aqueous pharmaceutical solution, as required, to achieve the pH from about 3.5 to about 4.7; wherein the osmolality of the aqueous pharmaceutical solution is about 560 mOsm/kg; and wherein the device is configured to deliver the unit dose to the patient by a single actuation.
2 . The unit dose of claim 1 , wherein the pH of the solution is about 4.3.
3 . The unit dose of claim 1 , wherein the citrate buffer is in an amount of about 0.2% to about 0.4% by weight based on the total weight of the aqueous pharmaceutical solution.
4 . The unit dose of claim 1 , wherein the unit dose maintains at least 98 wt % of the naloxone hydrochloride upon storage under the conditions of 40° C. for at least 1 month.
5 . The unit dose of claim 1 , wherein the unit dose maintains at least 98 wt % of the naloxone hydrochloride upon storage under the conditions of 40° C. for at least 3 months.
6 . The unit dose of claim 1 , wherein the unit dose maintains at least 98 wt % of the naloxone hydrochloride upon storage under the conditions of 40° C. for at least 6 months.
7 . The unit dose of claim 1 , wherein the unit dose maintains at least 98 wt % of the naloxone hydrochloride upon storage under the conditions of 40° C. for at least 9 months.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. application Ser. No. 17/882,014, filed Aug. 5, 2022, which is a continuation of International Application Number PCT/US2021/016873 filed Feb. 5, 2021, which claims priority to U.S. Provisional Application No. 62/970,629 filed Feb. 5, 2020, the contents of which are incorporated herein by reference. BACKGROUND Opioid receptors are G protein-coupled receptors (GPCRs) that are activated both by endogenous opioid peptides and by clinically important alkaloid analgesic drugs such as morphine. In the United States, mortality rates closely correlate with opioid sales. In 2008, approximately 36,450 people died from drug overdoses. At least 14,800 of these deaths involved prescription opioid analgesics. Moreover, according to the Substance Abuse and Mental Health Services Administration, the number/rate of Americans 12 years of age and older who currently abuse pain relievers has increased by 20 percent between 2002 and 2009. Naloxone is an opioid receptor antagonist that is approved for use by injection for the reversal of opioid overdose and for adjunct use in the treatment of septic shock. It is currently being used mainly in emergency departments and in ambulances by trained medical professionals. There have been efforts to expand its use by providing the drug to some patients with take-home opioid prescriptions and those who inject illicit drugs, potentially facilitating earlier administration of the drug. The Drug Overdose Prevention and Education (DOPE) Project was the first naloxone prescription program (NPP) established in partnership with a county health department (San Francisco Department of Public Health), and is one of the longest running NPPs in the USA. From September 2003 to December 2009, 1,942 individuals were trained and prescribed naloxone through the DOPE Project, of whom 24% returned to receive a naloxone refill, and 11% reported using naloxone during an overdose event. Of 399 overdose events where naloxone was used, participants reported that 89% were reversed. In addition, 83% of participants who reported overdose reversal attributed the reversal to their administration of naloxone, and fewer than 1% reported serious adverse effects. Naloxone has a relatively short half-life compared to some longer-acting opioid formulations. After a typical therapeutic dose of naloxone is administered to an opioid overdose patient, there is often the need to re-administer naloxone, in some cases even several times, and it is important to seek immediate medical attention. Furthermore, it has been suggested that in view of the growing opioid overdose crisis in the US, naloxone should be made available over-the-counter (OTC). Thus, there remains a need for storage-stable formulations that can enable untrained individuals to quickly deliver a therapeutically effective dose of a rapid-acting opioid receptor antagonist to an opioid overdose patient. The formulations described herein meet this and other needs. SUMMARY Described herein, inter alia, are pharmaceutical compositions comprising an opioid receptor antagonist such as naloxone or a pharmaceutically acceptable salt thereof or a hydrate thereof, devices configured to administer said compositions, kits comprising said compositions and devices, and methods of using said compositions in the treatment of opioid overdoses and symptoms thereof. In one embodiment, provided herein is a pharmaceutical composition comprising naloxone or a pharmaceutically acceptable salt thereof (e.g., naloxone hydrochloride) or a hydrate thereof (e.g., naloxone hydrochloride dihydrate) and a polyol (e.g., a polyol having a molecular weight less than 300 Da, e.g., propylene glycol or glycerin), wherein the composition is substantially free of a preservative. In another embodiment, provided herein are unit doses of the pharmaceutical compositions described herein. In one embodiment, provided herein is a device configured for intranasal administration of a pharmaceutical composition described herein to a subject (e.g., a patient in need thereof), wherein the device is configured for delivery of one dose of the pharmaceutical composition to the subject. In another embodiment, described herein is a device configured for intranasal administration of a pharmaceutical composition described herein to a subject (e.g., a patient in need thereof), wherein the device is configured for delivery of two doses of the pharmaceutical composition to the subject. In another embodiment, provided herein is a device configured for intranasal administration of one occurrence of a unit dose described herein to a subject (e.g., a patient in need thereof), wherein the device is configured for a single delivery of the unit dose to the subject. In another embodiment, provided herein is a device configured for intranasal administration of two independent occurrences of a unit dose described herein to a subject (e.g., a patient in n