NASAL IN-SITU GEL DRUG DELIVERY SYSTEMS FOR OSTEOPOROSIS: ADVANCES IN THERMORESPONSIVE AND MUCOADHESIVE FORMULATIONS

Abstract

Osteoporosis is a chronic metabolic bone disorder requiring sustained pharmacotherapy. Conventional oral drugs such as raloxifene and bisphosphonates are limited by poor bioavailability, gastrointestinal intolerance, and poor patient compliance. Nasal in-situ gel drug delivery systems represent a thrilling alternative by combining the advantages of the nasal route with the application of temperature-sensitive and mucoadhesive polymers to enhance drug absorption and residence time. This review emphasizes recent progress in nasal in-situ gel formulation for osteoporosis treatment, with attention to formulation approaches, pharmacokinetics, efficacy, safety, and regulatory aspects. The studies have shown increased systemic bioavailability (up to 13.4-fold for raloxifene), increased bone mineral density, and non-irritating, stable formulations appropriate for long-term administration. Further, employing FDA-approved drugs and GRAS-listed excipients allows development through the 505(b)(2) regulatory route. Although formulation achievement is met, limitations of nasal volume, mucosal tolerability, and clinical translatability still exist. Nasal in-situ gels are well-positioned to be non-invasive, scalable candidates for efficacious osteoporosis treatment.

KEYWORDS

Nasal In-situ gel, Osteoporosis, Raloxifene, Bisphosphonates, Mucoadhesive polymers, Thermoresponsive delivery, Bioavailability enhancement, Drug delivery system, GRAS excipients, 505(b)(2) pathway.