TRANSLATIONAL PHARMACOLOGICAL ANALYSIS OF LOCAL ORAL THERAPEUTICS (GAṆḌŪṢA, KAVALA, AND PRATISĀRAṆA) IN ŚĀRṄGADHARA SAṂHITĀ

Background: The Śārṅgadharasaṃhitā, a seminal 13th-century Ayurvedic compendium, systematically codifies local oral therapeutic procedures—Gaṇḍūṣa (mouth holding), Kavala (gargling), and Pratisāraṇa (topical powder application)—in its Madhyama and Uttara Khaṇḍas. Despite their clinical prevalence in traditional practice, these modalities lack comprehensive translational pharmacological frameworks connecting classical descriptions to modern mucosal drug delivery science. Objective: To establish a translational pharmacological framework analyzing Gaṇḍūṣa, Kavala, and Pratisāraṇa through integrated textual exegesis of Śārṅgadharasaṃhitā and contemporary oral mucosal drug delivery research. Methods: Systematic review of Śārṅgadharasaṃhitā chapters on Ganduṣa-Kavala-Pratisāraṇa Vidhi, correlated with modern pharmacological literature on buccal/sublingual absorption, mucoadhesion, permeability enhancement, and clinical studies on Ayurvedic oral formulations. Results: Classical procedures demonstrate sophisticated understanding of oral mucosal pharmacokinetics: Gaṇḍūṣa achieves static distension maximizing mucosal contact time; Kavala enables dynamic distribution with mechanical cleansing; Pratisāraṇa provides localized high-concentration powder application. Modern evidence confirms sublingual/buccal routes bypass hepatic first-pass metabolism, with thin mucosal layers (500–800 μm buccal; thinner sublingual) permitting rapid lipid-soluble compound absorption. Clinical trials show Khadira, Triphala, and Yashtimadhu-based Pratisāraṇa formulations effectively manage stomatitis, periodontitis, and oral ulcers. Conclusion: Gaṇḍūṣa, Kavala, and Pratisāraṇa represent pharmacologically sophisticated local delivery systems anticipating modern principles of mucoadhesion, permeability enhancement, and targeted mucosal therapy. A five-dimensional translational framework (HP1–HP5) is proposed for future standardization and clinical validation.