Cooperative Agreement 2231141

SBIR PHASE II: DESIGN OPTIMIZATION AND MANUFACTURING SCALE-UP OF ORAL DOSAGES WITH ENVIRONMENTALLY RESPONSIVE POLYMERS -THE BROADER IMPACT/COMMERCIAL POTENTIAL OF THIS SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE II PROJECT EXPANDS THE UNDERSTANDING AND APPLICATION OF ENVIRONMENTALLY RESPONSIVE MATERIALS IN PHARMACEUTICAL PRODUCTS. THE LIMITATIONS OF CURRENT INACTIVE INGREDIENTS CAUSE 30% OF NEW DRUGS TO BE TERMINATED AND LEAVE ROUGHLY HALF OF APPROVED DRUG PRODUCTS WITH ROOM FOR IMPROVED EFFICACY. THUS, MORE EFFECTIVE MATERIALS ARE VITAL TO CONTINUE IMPROVING PUBLIC HEALTH VIA PRESCRIPTION DRUGS. AS A RISK-AVERSE INDUSTRY, PHARMACEUTICAL INNOVATION PRIORITIZES THE ACTIVE INGREDIENTS THAT ADDRESS DISEASE. HOWEVER, THIS PROJECT COULD DEMONSTRATE THAT INNOVATIVE INACTIVE INGREDIENTS CAN ENHANCE DRUG PRODUCT EFFICACY WITH MINIMAL ADDITIONAL RISK TO CLINICAL TRANSLATION AND COMMERCIALIZATION. THIS PROJECT WILL PROGRESS DRUG PRODUCT DESIGN TO EFFECTIVELY INCORPORATE RESPONSIVE MATERIALS AND CORRESPONDING MANUFACTURING PRACTICES TO MEET QUALITY STANDARDS, WITH REGULATORY GUIDANCE FROM THE FDA NOVEL EXCIPIENT REVIEW PROGRAM. THESE DEVELOPMENTS COULD ESTABLISH HIGHER STANDARDS OF DRUG PERFORMANCE. THE IMPACT OF A BROADLY COMPATIBLE MATERIAL WHICH CAN SERVE AS A HIGHLY EFFECTIVE DRUG DELIVERY TECHNOLOGY IS FASTER AND MORE COMPATIBLE DRUG MANUFACTURING PROCESS. THE POTENTIAL BENEFIT WILL BE BROADER AVAILABILITY OF PRESCRIPTION DRUGS WITH LOWER PRICES. THE PROPOSED PROJECT HAS TWO PRIMARY OBJECTIVES: (1) ESTABLISH A SCALED-UP MANUFACTURING PROCESS AND ASSOCIATED ANALYTICAL METHODS FOR THE PRODUCTION AND QUALITY CONTROL, RESPECTIVELY, OF DRUG PRODUCTS UTILIZING A NOVEL ENVIRONMENTALLY RESPONSIVE POLYMER, AND (2) DESIGN AN EFFECTIVE AND SHELF-STABLE CAPSULE FORMULATION FOR THE DRUG FULVESTRANT USING THE SAME POLYMER. THE PRIMARY HURDLES INCLUDE CONVERTING CURRENT LAB-SCALE MANUFACTURING PROTOCOLS TO BE COMPATIBLE WITH COMMERCIAL-SCALE MANUFACTURING EQUIPMENT AND ENSURING THE CAPSULE FORMULATION IS SHELF-STABLE WHILE RETAINING HIGHLY EFFECTIVE ORAL DRUG DELIVERY METRICS. TO OVERCOME THESE CHALLENGES, THE RESEARCH AND DEVELOPMENT PLAN WILL FIRST VALIDATE ANALYTICAL METHODS FOR CRITICAL QUALITY ATTRIBUTES OF DRUG PRODUCT INTERMEDIATES, WHICH WILL THEN BE IMPLEMENTED DURING MANUFACTURING SCALE-UP AND FULVESTRANT CAPSULE DESIGN. THESE GOALS WILL HELP IDENTIFY PROCESSING PARAMETERS AND FORMULATION COMPOSITION THAT BALANCE LOW OPERATING EXPENSE AND HIGH-PERFORMANCE METRICS. THE FINAL DELIVERABLE WILL BE A DRUG MASTER FILE (DMF) SUMMARIZING THE MANUFACTURING AND QUALITY CONTROL PROCESSES FOR DRUG PRODUCTS UTILIZING AN ENVIRONMENTALLY RESPONSIVE POLYMER. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.