Bioavailability enhancement and improvement

For drugs with low solubility or bioavailability, Encap have a range of formulation options and technologies which will give drugs the best chance of success. These include solid solutions and solid suspensions of drugs in polymeric vehicles, emulsions and self emulsifying lipidic systems.

 Lipidic Formulations

Liquid and semi-solid filled hard capsule formulations are also ideally suited to compounds with low aqueous solubility, poor permeability and consequently low or variable bioavailability. Formulations which increase the solubility of the active or indeed present the drug as a solution can have a significant impact on the bioavailability of such drugs. Lipidic vehicles are generally well absorbed from the GI tract and in many cases this approach can significantly improve the oral bioavailability compared with administration of the solid drug substance. Encap has expertise in the use of self-emulsifying vehicles and has developed a number of self-emulsifying drug delivery systems (SEDDS) and self-microemulsifying drug delivery systems (SMEDDS) for the oral administration of drugs with poor water solubility. These are formulations which form emulsions or micro emulsions spontaneously on contact with aqueous media. An example of a marketed product that uses a SMEDDS type formulation is Neoral (Novartis) for oral administration of cyclosporine. In addition, Encap can offer the possibility to explore formulation screening for this type of formulation using Gattefosse kits. Encap have experience of a wide range of functional ‘bioavailability enhancer' excipients which are fully approved from a Regulatory perspective and include the screening of such excipients during pre-formulation studies.

Solid Solutions; Solid Dispersions

A formulation strategy for poorly soluble drugs is the use of solid solutions, which are molecular dispersions of the drug molecules in a polymer matrix. This conversion of the drug into the amorphous state produces material which dissolves more rapidly than the corresponding crystalline drug substance. The incorporation of the drug substance into hydrophilic polymeric materials such as polyvinylpyrollidone (PVP) and polyethylene glycol (e.g. PEG6000) can produce additional solubility enhancing effects.
Solid solutions can be prepared by dissolving the drug and the polymer in a suitable volatile solvent. On removing the solvent (by spray drying) an amorphous drug/polymer complex is formed. In some cases it is possible to dissolve the drug in the molten polymer and fill directly into hard capsules. On cooling, the drug is entrapped in an amorphous state within the water-soluble matrix.
In many cases, improvements in drug dissolution and bioavailability can also be achieved using dispersions or suspensions of drugs in appropriate vehicles which are suitable for filling into hard shell capsules.