# Injectable naltrexone 2-month depot formulations

> **NIH NIH UG3** · PURDUE UNIVERSITY · 2020 · $2,148,235

## Abstract

Project Summary
Naltrexone (NTX) has been proven as an important therapy in helping patients overcome opioid addition and in
preventing overdose. Past usage of NTX has been shown to be both extremely safe and effective. Unfortunately, one
of the major problems with NTX is noncompliance in therapy. To combat this issue, a system must be developed to
deliver NTX for longer durations than currently available with a more patiently friendly format, specifically the duration
of action, injection quantity/volume, and syringe needle size. With the basis of this program supporting the discovery
and development of medications to prevent and treat opioid use disorders and overdose, rapid advancement towards a
viable product for new dose regimens and ease of administration for increased adherence should be one of the first,
scientifically sound, and robust choices moving forward.
PLGA-based drug delivery systems have been used successfully in a number of small molecule products and are the
most widely utilized and studied biocompatible polymer systems in controlled release. Therefore, the regulatory and
development hurdles with the FDA will be `lower' than with other novel excipients or technologies. The goal of this
research and product development plan is to submit a phase I application for a 2-month NTX formulation with favorable
release kinetics and a patient-friendly format. Our preliminary data indicate two types of current, laboratory based
systems can provide both a high drug loading and controllable release kinetics resulting of NTX for at least 2 months.
The Specific Aim of this project is to optimize and bridge our laboratory scale 2-month injectable NTX delivery
formulation to phase 1 clinical trials using 380 mg of NTX with a microparticle size of less than 100 µm for a less
painful injection The Sub-Aims for the UG3 phase are: (i) Establish the design space for the two 2-month NTX (2M-
NTX) formulations: Early Release (ER) and Delayed Release (DR); (ii) In vivo pharmacokinetic evaluations of 2M-
NTX-ER and 2M-NTX-DR formulations; and for the UH3 phase (iii) GMP manufacturing scale-up of the lead candidate
formulation; (iv) Lead candidate formulation nonclinical characterization; and (v) 505b2 IND submission for a phase I
clinical trial. The innovation in this technology is the ability to control the NTX release kinetics while eliminating the
initial burst; based on our mechanistic understanding of the PLGA microparticle formation process, using PLGAs with
specific molecular properties, and providing tight control over the manufacturing conditions. This innovation has
allowed us to design two specific types of formulations to aid in combating the opioid epidemic: (1) ER providing near
zero-order release kinetics for two months and (2) DR providing an initial lag phase of 7-10 days, where minimal NTX
release occurs, so it can be administered to patients who are still under the influence of opioids without precipitating
withdrawal symptoms. PLGA-b...

## Key facts

- **NIH application ID:** 9897469
- **Project number:** 5UG3DA048774-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** KINAM PARK
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,148,235
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897469

## Citation

> US National Institutes of Health, RePORTER application 9897469, Injectable naltrexone 2-month depot formulations (5UG3DA048774-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897469. Licensed CC0.

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