Mechanisms of solvent evaporation encapsulation processes: prediction of solvent evaporation rate.
The mechanism of organic solvent evaporation during microencapsulation and its role during microsphere hardening has been investigated. Evaporation and encapsulation studies were carried out in a jacketed beaker, filled with aqueous hardening solution, which was maintained at constant temperature and constant stirring rate in the turbulent regime. Evaporation of dissolved methylene chloride (MC), ethyl acetate (EA), and acetonitrile (ACN) was examined by the decline in organic solvent concentration in the hardening bath, which was monitored by gas chromatography. The evaporation from the bath followed first-order kinetics under dilute conditions (e.g., MC < 3 mg/mL), yielding an overall permeability coefficient, P. The value of P was theoretically related to the Kolmogorov length-scale of turbulence under conditions that favor liquid-side transport control. According to theory, factors that favored liquid-phase control (as opposed to gas-phase control) were those that favored a high Henry's law constant [i.e., elevated temperature near the normal boiling point (bp) of the organic solvent] and properties of the dissolved organic solvent (i.e., low normal bp and low aqueous solubility). These theoretical hypotheses were confirmed by (1) correlating the experimentally determined P with process variables raised to the appropriate power according to theory, r(2) = 0.95 (i.e., P approximately rotational speed, omega(3/4), impeller diameter, d (5/4), volume of hardening bath, V(-1/4), and the product of kinematic viscosity and diffusion coefficient, nu(-5/12)D (2/3)), and (2) illustrating that at constant temperature, the tendency of the evaporation system to obey liquid-side transport control follows the same order of increasing Henry's law constant (i.e., MC > EA > ACN). To establish the relationship of evaporation with microsphere hardening, the decline in MC concentration was determined in both the continuous and dispersed polymer phases during microencapsulation. By applying a mass balance with respect to MC in the hardening bath, the cumulative hardening profile of the microspheres was accurately predicted from the interpolating functions of the kinetics of MC loss from the bath with and without polymer added. These results have potential use for microsphere formulation, design of encapsulation apparatus, and scale up of microsphere production.
Wang
J
J
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210, USA.
Schwendeman
S P
SP
D000465:Algorithms; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D002849:Chromatography, Gas; D004339:Drug Compounding; D008863:Microspheres; D008962:Models, Theoretical; D010539:Permeability; D012997:Solvents; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000737:chemistry; D014835:Volatilization
D000893:Anti-Inflammatory Agents; D012997:Solvents; D014222:Triamcinolone Acetonide