Space motion sickness frequently affects astronauts during the first few days of space travel. One of the current treatments for space motion sickness, promethazine, is most effective as an injection into the muscle. But, it can cause pain and irritation and has variable effectiveness in different individuals. To minimize the injection’s negative side effects and variability of effectiveness, Dr. Lakshmi Putcha and colleagues at the Johnson Space Center are developing a noninvasive dosage form of promethazine for intranasal delivery. Chemical engineers at the Southwest Research Institute are collaborating in the formulation development. Once a prototype formulation is developed, it will be tested for shelf life and drug delivery rate. Toxicology and bioavailability of the formulation will be determined in an animal model.
Overview
Microcapsule Gel Formulation of Promethazine Hydrochloride for Intranasal Administration
Principal Investigator:
Lakshmi Putcha, Ph.D.
Organization:
NASA-Johnson Space Center
Technical Summary
A continuing challenge for space medical operations at NASA is the management of pathology associated with neurovestibular adaptation during spaceflight. A primary manifestation of this problem, particularly in the first few flight days of shuttle missions, is space motion sickness (SMS). The current treatment of choice for symptoms associated with SMS is promethazine (PMZ). Although oral tablets and rectal suppositories have been used during spaceflights, the intramuscular route appears to be most effective. On the other hand, intramuscular administration of drugs is an invasive procedure and PMZ causes irritation at the site of injection. A key research topic in the Smart Medical Systems area is development of novel therapeutic modalities for remote site medical operations such as space missions. In response to this initiative, the goal of this research is to develop an intranasal dosage formulation of PMZ that will provide crewmembers with a noninvasive means of self-administering SMS medications. Accordingly, the following three aims will be addressed:
- Develop a microencapsulated, pH-balanced gel dosage formulation and a combination form with a corticosteroid for intranasal administration of PMZ;
- Establish the release kinetics and shelf life of the optimized dosage forms; and
- Assess bioavailability, nasal mucosal irritability and toxicity of the selected dosage forms in rats.
The proposed formulation development will focus on tailoring the release characteristics of the dosage form to optimize therapeutic index and minimize irritability at the site of administration. Once the optimal dosage form has been identified based on release kinetics and stability characteristics, bioavailability, nasal irritability and toxicity after single and multiple dose administration will be assessed in an animal model. Development of an intranasal drug delivery system for motion sickness treatment will benefit pharmacotherapeutics in space as well as on Earth.
This project's funding ended in 2003