Drug Release from the Water-in-Oil-in-Water Multiple Emulsion in Vitro. II. Effects of the Addition of Hydrophilic Surfactants to the Internal Aqueous Compartment on the Release Rate of Secretin

For the application of water-in-oil-in-water (w/o/w) emulsions to a nasal dosage form of secretin, permeation tests were conducted in vitro to assess the effects of hydrophilic surfactants in the internal aqueous compartment on the release rate of secretin. The amount of secretin that permeated through an artificial membrane from a donor cell to a receptor cell was affected by the addition of sodium chloride or sodium alkylsulfonate to the internal aqueous compartment of w/o/w emulsions in the donor cell. Sodium chloride decreased apparent permeation rate constants from the internal aqueous compartment to the external aqueous phase (K'1) as the difference in osmolartiy between the internal compartment and the external phase increased. While sodium alkylsulfonates increased K'1 in proportion to the values of (partition coefficient between the oil phase and the internal aqueous phase/partition coefficient between the oil phase and the external aqueous phase)/osmolarity ratio of the internal aqueous phase to the external aqueous phase. These results demonstrate that the release rate of secretion from w/o/w emulsions are affected by partition of the drug between aqueous and oil phases and by osmotic difference between the outer and internal phases.