Microbubble-encapsulation of actives for controlled release and its application to the taste-masking of acetaminophen

Abstract

In this work we present a new encapsulation method that allows for the controlled release of drugs under simulated small intestinal conditions. This method consists of encapsulation within microbubbles and is characterized by an unprecedented combination of excellent barrier properties and fast and complete triggered release. The method was applied to produce a drink containing taste-masked acetaminophen as a model drug. Micronized acetaminophen (paracetamol) was dispersed in cyclohexane containing pharma-approved hydrophobized silica particles and the resulting dispersion was emulsified in an aqueous phase containing dispersed hydrophobized silica particles and dissolved maltodextrin. The resulting solid-in-oil-in-water emulsion was washed to remove unencapsulated acetaminophen and subsequently freeze-dried to remove both the water and the cyclohexane. This produced a dry material that after reconstitution in water created a suspension of microbubbles containing acetaminophen particles, i.e. a solid-in-gas-in-water dispersion. The encapsulation efficiency was well over 90% and hardly any acetaminophen escaped from the microbubbles during storage for 24 h in aqueous solution. Also, encapsulates were stable in the presence of saliva as well as during in vitro incubation with stomach juice. In line with this, sensory tests showed an excellent masking of the taste of the drug. In vitro incubation with simulated intestinal fluid containing bile salts triggered fast and near complete release of the encapsulated acetaminophen, which should assure good bioavailability in vivo. The described encapsulates that are stable for at least days, are thus expected to be suitable for taste-masking or enteric release applications in liquid formulations, including foods.