Rethinking gastro-resistant enteric encapsulations

Designing a gastro-resistant coating with targeted release in the intestine is complicated by highly variable stomach transition times. Stomach transition times can differ from several minutes to many hours depending on individual fed state and physiological variability. Employing a time dependent gastro-resistant mechanism is therefore not an option.

On the other hand the transit time in the small intestine is relatively constant and the intestinal release mechanism can therefore be time dependent. Our specialized encapsulation technology can be designed to dissolve either rapidly for targeted delivery in the upper parts of the small intestine, or to dissolve slowly for targeted release in colon.

The encapsulation technology use the pH difference between the stomach and the intestine to govern payload release. Our coating is tight and stable under acidic pH in the stomach, and dissolves at neutral pH in the intestine. The coating dissolution rate is constant at neutral pH and the encapsulation can be designed to target early release in the upper parts of the small intestine or late release in the colon.

Release in the upper small intestine

Both images: Modified from Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2).

Release in the colon

The encapsulation technology is built around a two-component coating consisting of:

  1. Bacterial cellulose (BC). BC is a pure form of cellulose. Cellulose fibres are not digested in the human GI tract as there are no naturally occurring cellulases.
  2. pH dependent cellulases that are inhibited in the acidic stomach and digest BC in the pH neutral intestine 

The encapsulation technology is built around a two-component coating consisting of:

  1. Bacterial cellulose (BC). BC is a pure form of cellulose. Cellulose fibres are not digested in the human GI tract as there are no naturally occurring cellulases.
  2. pH dependent cellulases that are inhibited in the acidic stomach and digest BC in the pH neutral intestine 

A technical proof of concept of the technology was obtained in collaboration with central players in the field. By infusing the cellulase into BC in a simple process a film is obtained with the cellulase bound in the BC membrane.

A functional process design has been developed, and an understanding of central process control parameters has been achieved.

The technology is suitable for the development of a broad range of highly differentiated new pharmaceutical, prebiotics/probiotics and nutraceutical products. This includes drugs and prebiotics/probiotics already marketed but formulated with a less efficient enteric coating technology.

The raw materials for production of the encapsulation is cellulose and cellulases. Cellulose is already well known in pharmaceutical production where it has been used for many years for many purposes. Cellulases is a main component in the production of biofuels and has been intensively studied for decades. The production process for the encapsulation technology is a new combination of  known bioprocess steps, and the cost per capsule is expected to be relatively low.

The advantage of the encapsulation being based on biocompatible non-toxic ingredients are several. This feature is projected to allow for an easy regulatory approval of drugs utilizing the technology, and few restrictions to its use in humans.