# Micronized salsalate in a parenteral formulation is a safe and effective analgesic for acute postoperative pain management

> **NIH NIH R44** · RH NANOPHARMACUETICALS L.L.C. · 2020 · $85,000

## Abstract

SUMMARY: The White House has initiated an aggressive campaign to combat the current opioid crisis that is
affecting all levels of the American way of life. The opioid crisis has emerged from multiple fronts. Among these
various fronts, the continued use of opioids in the post-operative area is a growing addiction risk. Current post-
operative pain management utilizes a multimodal pain management strategy, which includes opioids and non-
opioids (NSAIDs). These two treatment strategies have significant health care cost implications due to their
adverse events and addiction risks. Opioids have serious adverse effects such as nausea, vomiting,
respiratory depression, urinary retention, hypotension, and long-term addiction risks. Non-opioids such as
NSAIDs, both in oral and parenteral formulations, are an essential part of a multimodal post-operative pain
management strategy for their opioid sparing capabilities. However, NSAIDs (Cyclooxygenase (Cox)-1/2
inhibitors) have serious adverse events such as GI bleeding, cardiovascular events, and systemic bleeding.
This current state of affairs has created an unmet need for an effective parenteral/oral analgesic for acute post-
operative pain management without the risks of opioid addiction. Salsalate, a dimer or salicylic acid, although a
non-FDA-approved drug, is currently available in oral dosage for the treatment of osteoarthritis and rheumatoid
arthritis. Salsalate works at multiple levels to target multiple steps along the surgical pain pathway. Salsalate
through its active metabolite, salicylic acid (SA), reduces NF-κB activation via IKK-kinase beta inhibition, and
has no direct binding to cyclooxygenase 1 (Cox-1); therefore, does not affect function of platelets, resulting in a
safer hematological and gastrointestinal safety profile 1. RH Nanopharmaceuticals (RH Nano) had a successful
Pre-IND application review for current oral salsalate through the FDA 505(b)(2) regulatory pathway to submit
an IND in the next few months. FDA has confirmed that salsalate is likely to be considered a new chemical
entity (NCE) for an initial New Drug Application (NDA). RH Nano has also developed a micronized version of
salsalate (M-salsalate) for oral and parenteral administration. Our preliminary testing shows that in comparison
with current oral salsalate, M-salsalate has an improved pharmacokinetic profile including a shorter Tmax,
higher Cmax, and larger area under the curve (AUC), resulting in enhanced biodistribution. It is expected to
have the same safety profile as the oral salsalate. The President’s Commission on “Combating Drug Addiction
and the Opioid Crisis” has recommended to the President of the United States that “individuals with acute or
chronic pain must have access to non-opioid pain management options”, and the National Institute on Drug
Abuse (NIDA) has a strong interest on “non-opioid medications to treat pain in outpatient subjects, including
opioid sparing strategies”. With these needs in mind...

## Key facts

- **NIH application ID:** 10048402
- **Project number:** 3R44NS113749-01S1
- **Recipient organization:** RH NANOPHARMACUETICALS L.L.C.
- **Principal Investigator:** Joel Steven Ross
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $85,000
- **Award type:** 3
- **Project period:** 2019-11-01 → 2020-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048402

## Citation

> US National Institutes of Health, RePORTER application 10048402, Micronized salsalate in a parenteral formulation is a safe and effective analgesic for acute postoperative pain management (3R44NS113749-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10048402. Licensed CC0.

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