Egalet

Egalet Corporation is a specialty pharmaceutical company that focuses on the commercialization and development of abuse resistant formulations of opioids and other pain care drugs. It was founded as a private company in 1995 in Værløse, Denmark, and now operates as a publicly traded American company headquartered in Wayne, Pennsylvania, a suburb west of the city of Philadelphia. The consolidated company has offices in the UK, the United, and Denmark. All research, development, and manufacturing is carried out in the Denmark offices. Egalet trades on the NASDAQ exchange under the trading symbol EGLT, and as of June 2018, is loss-making.

Egalet made a pill that allows for the controlled release of drugs; it is made up of an inner matrix, which contains the active ingredient, and an outer coating shell made up of proprietary polymers.

The matrix, or inner portion of the pill, contains the dispersed drug. The matrix is designed to erode when it comes into contact with water, but not until the desired point of release, in order to avoid hydrolysis and the reduction of enzymatic activity. The active substance is then released with a zero order release which ensures that a steady amount of the drug is released over time. This minimizes fluctuations while maximizing the amount of time the drug remains within the therapeutic window.

The matrix is protected by the outer shell coating made of a cellulose derivative with thermoplastic properties. This derivative is relatively insoluble in an aqueous solution. The shell also contains a second cellulose derivative which is soluble in an aqueous solution; a plasticizer which promotes plasticity and reduces brittleness, and a filler which increases volume. The outer shell protects the inner matrix, which can consist of chemically unstable substances, such as those with low melting and boiling points, and water-insoluble compounds. Also, this protective shell significantly increases the shelf life of the substance. The shell composition allows for controlled release of the matrix in both the stomach and the intestines despite the varying pH, agitation, etc.

Once ingested, the shell is separated from the matrix through water diffusion, polymer hydration, disentanglement, and dissolution, and the matrix can then carry out its intended function.

By altering the composition of the shell and matrix, many drug formulations and ways of release can be achieved. The altering of the shape and surface area of the pill can also affect release times. The pills are made with injection molding in order to complete the creation process in one fluid step.

Egalet uses an amorphous state of the active ingredient. An amorphous state requires the formation of a higher energy solid state form. Creating an amorphous form of dispersion is important in order to be able to use poorly water-soluble drugs as well as to improve oral bioavailability. The current pill enables the control of this amorphous phase as well as the controlled release of the active substance from the coated matrix system. The inner matrix has been designed for improved bioavailability, for specific situations where an insoluble active substance is needed, and to prevent abuse or misuse of the matrix.

The matrix composition is made up of the following:

1. a mixture of a first (polyethylene glycols and/or polyethylene oxides) and second polymers (block co-polymer of ethylene oxide and/or propylene oxide) that have plasticizing characteristics. The melting points of the polymers are at the most 200 °C. The combination of the polyethylene oxides and the blocking co-polymer enable the control of the amorphous state. Some examples of the second block polymers used include poly(ethylene-glycol-b-(DL-lactic acid-co-glycolic acid)-b-ethylene glycol (PEG-PLGA PEG), poly((DL-lactic acid-co-glycolic acid)-g-ethylene glycol) (PLGA-g-PEG), poloxamers and polyethylene oxide-polypropylene oxide (PEO-PPO).

2. a therapeutically, and/or diagnostically active substance.

The first polymer is a polyethylene glycol and/or a polyethylene oxide. Polyethylene glycols (which are denoted as polyethylene oxides when the molecular weight is above about 100,000) are mixtures of condensation polymers of ethylene glycol. In preferable conditions, the first polymer has a molecular weight of about 35,000 daltons. Mixtures of PEG’s may be used to get the ideal molecular weight for specific formulations.