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In certain embodiments, any controlled release otic formulation described herein increases the exposure of a therapeutic agent and increases the length of time that the concentration of a therapeutic agent is above C min by about 30%, about 40%, about 50%, about 60%, about 70%, about 80% or about 90% compared to a formulation or composition that is not a controlled release otic formulation or composition

By calculating parameters such as the kernel density analysis model and the nearest neighbor index, it systematically analyzes the characteristics of spatial and temporal distribution