Fundamentals of release mechanism interpretation in multiparticulate systems: determination of substrate release from single microcapsules and relation between individual and ensemble release kinetics

For assessing theories underlying release kinetics of contents from ensembles of microparticles in multiparticle dispersions, population release studies are incapable of revealing the operative physicochemical mechanism, in spite of attempts by many authors to interpret such cumulative data. The present study pioneers techniques for determining release kinetics from single microparticles, using microcapsules as model systems with microconductimetric or spectrophotometric measurement of contents released into the external medium. In four systems giving overall first-order release from populations, the individuals all released their contents at constant rates almost to total payload. A statistical model relating the sum of individual release to cumulative release was applied to the data. It was based on the distribution of two fundamental parameters of the individuals, m_∞ the payload and t_∞ the time to complete release. Statistical analysis of the experimental data validated the proposed relation in the four systems. The conditions required to obtain first-order cumulative kinetics from summated single constant rate data are either: (1) gamma-distribution with shape parameter = 2 of t_∞ and independence of m_∞ and t_∞; or (2) exponential distribution of t_∞ and correlation betw m_∞ and t_∞. Cumulative kinetics and rate constants based on an approximation to a standard release equation are useful for characterization of batch release properties (e.g. in checking repeatability, effects of production variables, sustained release character under controlled conditions) but do not reveal the underlying release mechanism or the actual distribution of parameters, which require studies on individuals. Cumulative kinetics may in fact be altered if the distribution profile of the population undergoes accidental or pre-determined change.