A continuing challenge for space medical operations at NASA is the management of pathology associated with neurovestibular adaptation during space flight. 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 space flights, 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 of the NSBRI 99-02 research announcement 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 non-invasive means of self-administering SMS medications. Accordingly, the following three aims will be addressed:

1. Develop a microencapsulated, pH-balanced gel dosage formulation and a combination form with a corticosteroid for intranasal administration of PMZ;
2. Establish the release kinetics and shelf life of the optimized dosage forms; and
3. 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.

Project Description