# Sustained Delivery of Tizanidine for Maintenance Treatment of Moderate to Severe Spasticity

> **NIH NIH R44** · DELPOR, INC. · 2022 · $1,246,488

## Abstract

Spasticity is an increase in muscle tone and uncontrolled, repetitive, involuntary contractions of skeletal
muscles. Spasticity presents as upper motor neuron symptoms in patients with central nervous system
pathology such as cerebral palsy (CP), multiple sclerosis (MS), traumatic brain injury (TBI) and spinal cord
injury (SCI). Two thirds of all children with CP suffer from spasticity. Children with severe spastic CP are
highly limited in daily life activities causing a reduced quality of life. The proportion of MS patients with
inadequate symptom treatment for spasticity ranges from 46%- 52.5%.
Tizanidine and Baclofen are two of the most prescribed drugs for spasticity treatment. Both drugs have a very
short half-life and need to be administered 3-4 times per day. These drugs result in several side effects at high
plasma levels such as muscle weakness, nausea, somnolence and paraesthesia, limiting their clinical utility,
particularly in the palliative maintenance setting. Baclofen is also available as an intrathecal infusion pump
(ITB). ITB reduces the spasticity of affected patients and represents the standard of care for severe spastic
CP. However, intrathecal therapy requires a 1-3 hour surgery done under local or general anesthesia and
requiring a hospital stay at times. ITB also introduces risks related to the pump and the robustness and
placement of the intrathecal catheter. The combination of comorbidities predispose patients to ITB
complications including septic infections, and meningitis in 8.7% of patients. In the pediatric population, the
rate of complications is much higher (31%) requiring surgical management over a 3-year treatment period.
The proposed product is a small non-mechanical (passive) subcutaneous implant (reservoir) which will deliver
consistent therapeutic levels of tizanidine during a period of 4 months or longer. The implant body is made of
titanium and it is implanted subcutaneously in the upper arm via a trocar, with local anesthetic during a simple
10-minute in-office procedure. The technology is based on a unique formulation; a mixture of tizanidine and
certain acid generating excipients, such as partially soluble acids. The solubilization of the acid keeps pH
within the reservoir low, and in doing so, promotes the passive outward diffusion of tizanidine. The solubility of
tizanidine is greatly enhanced upon protonation by acids, and thus the concentration gradient driving flux is
greater under the acidic conditions provided by constant excipient dissolution within the reservoir. The
technology has been validated clinically with another drug (risperidone), which is currently in a Phase II clinical
trial. The preclinical proof of concept has already been completed as part of the phase 1 grant award. The
current effort will complete all activities required for the successful preparation and submission of an IND, so a
Phase I clinical study can be launched. The proposed tizanidine system is expected to provide enhan...

## Key facts

- **NIH application ID:** 10490906
- **Project number:** 5R44NS110135-03
- **Recipient organization:** DELPOR, INC.
- **Principal Investigator:** Gregory Watkins
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,246,488
- **Award type:** 5
- **Project period:** 2019-04-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490906

## Citation

> US National Institutes of Health, RePORTER application 10490906, Sustained Delivery of Tizanidine for Maintenance Treatment of Moderate to Severe Spasticity (5R44NS110135-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10490906. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*