Oral drug delivery is the most favored route of drug administration. However, poor oral bioavailability is a leading reason for weak clinical efficacy. Clearly, no matter how much of a drug you take, if it doesn’t reach the target organ in sufficient doses, it isn’t going to do much good! With estimations that up to 70% of drug molecules are insufficiently soluble for good bioavailability, this poses a serious challenge for drug developers seeking to demonstrate the efficacy of their products.
Formulation scientists have adopted various strategies to enhance drug bioavailability. Their approaches have the potential not just to improve the success rates of new and innovative treatments, but also to provide improved formulations of old medications. In fact, the large number of poorly soluble drugs on the market has provided profitable strategies for more than one pharma company to file NDAs for improved formulations of older drugs with enhanced bioavailability profiles.
Enhanced bioavailability also means that lower doses of these improved formulations might be sufficient, potentially reducing the overall drug load and minimizing side effects. Furthermore, as APIs become more potent (due to higher bioavailability), the lower loads of drug required could result in smaller drug manufacturing volumes, reduced environmental impact and a smaller manufacturing footprint.
Modern approaches to enhancing drug bioavailability have generally focussed on the molecular optimization of the drug molecule. Broadly speaking, four technologies are used to overcome these challenges: hot melt extrusion, spray drying, lipid-based formulations and particle sizing.
Hot melt extrusion and spray drying both enhance the absorption of poorly soluble drugs through the formulation of ‘amorphous solid dispersions’. Spray Drying and hot melt extrusion are the main manufacturing processes to obtain these amorphous materials, which represent the fastest growing approach to overcoming poor bioavailability. In practice, spray drying is more suitable for heat-sensitive products such as biologics, and it is often the preferred route for inhalable drugs, while hot melt extrusion can be more efficient in developing some poorly water-soluble drugs in hydrophilic carriers.
Lipid-based carrier systems have long been a focus of interest. The incorporation of poorly water-soluble active drug molecules into inert oils, emulsions, self-emulsifying formulations or liposomes, for example, can provide a vehicle to enhance absorption and bioavailability. These delivery systems have been used for decades but, more recently, they have been used for the delivery of relatively large DNA and RNA-based drugs, including plasmids, antisense oligonucleotides and ribozymes.
Particle sizing for enhanced bioavailability typically involves increasing the surface area of a drug molecule by reducing its particle size. Although particle size may have little effect on drugs that are readily water soluble, reducing the size of poorly water-soluble drug molecules can lead to higher dissolution rates due to the larger surface area to volume ratio and, therefore, a better chance for faster absorption. However, particle size reduction may not be useful for very fine powders with poor wettability and handling difficulties.
The choice of technology will depend on the drug molecule in question, and the way in which it will be administered in practice. However, while contract services for lipid-based carrier systems and particle sizing are widely available, hot melt extrusion and spray drying are still niche offerings. As a snapshot view of the global situation, of 1,589 listed CMOs, the Contract Pharma directory lists only 38 offering Read More
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