Biphasic release tablet, enhanced oral bioavailability for a poorly water soluble API - tablet matrix and oral gel for sublingual administration.

Biphasic release tablet

The challenge: The client required a tablet which would release a proportion of an active compound immediately after swallowing and the remainder of the active released slowly over several hours.

The solution: The required drug release profile was achieved by incorporating a proportion of the drug in a tablet core (designed to retard the drug release) and coating the tablet core with a water soluble coating containing the remainder of the drug (providing an immediate release element).

Enhanced oral bioavailability for a poorly water soluble API – tablet matrix

The challenge: The client presented an investigational drug which exhibited very poor water solubility, resulting in low and variable oral bioavailability (when administered in a capsule formulation). The project brief was to enhance the oral bioavailability of the drug – preferably using a tablet formulation.

The solution: Two different tablet formulation strategies were considered:

• Tablet one – Direct compression matrix
• Tablet two – Melt granulation-type matrixm, using a block copolymer as joint binding agent/solubilising agent
• The oral bioavailability for three presentations (Capsule formulation, tablet one formulation and tablet two formulation) was determined in human volunteers

The tablet two formulation (containing the block copolymer) significantly improved the oral bioavailability of the API. Even the conventional tablet formulation (tablet one) exhibited a 50% increase in bioavailability.

Oral gel – for sublingual administration

The challenge: The client required a formulation for delivery of the API through buccal absorption, preferably as a water-based gel.

The solution: For efficient absorption through the buccal membrane it was necessary to adjust the pH to ensure that the API was in its non-ionised state – which consequently significantly reduced the water solubility of the API. Several solubility enhancing options were evaluated, including use of non-ionic surfactants and selection of suitable co-solvents.

A suitable gel formulation was successfully developed – which maintained the drug in its non-ionised form and retained it in solution – using a combination of co-solvents and an appropriate beta-cyclodextrin derivative.