Tuesday, 15 October 2019

Techniques for Improving Drug Solubility

Solubility is one of the most important phenomena in chemistry, pharmaceuticals and any number of other disciplines and industries. In the development of drugs, the ability of a solvent to create a uniform, homogenous system is critical to ensure that drug achieves the desired effect in patients.

A guest post by Megan Ray Nichols

The following list provides a look at some of the more modern and common techniques for improving drug solubility and enhancing the human body's ability to absorb and use them.

1. Reduce Particle Sizes

Reducing the size of the drug particles themselves is one of the most straightforward techniques for improving the final compound's solubility. The smaller the particle, the more surface area is exposed, and the more it can interact with the solvent.

You can apply this principle in several ways. Here are some of the most common:

  • Comminution: These processes include grinding, vibrating or crushing the particles until they reach the desired size. This solution is not perfect, however, as the physical agitation may degrade the drug’s effectiveness.
  • Spray drying: Food and chemical manufacturing entities have long used spray drying, and it has more recently gained acceptance in the drug industries. Spray drying yields an amorphous material that is many times more soluble and bioavailable than its previous crystalline form.
  • Micronization: Modern techniques for micronization involve applying supercritical fluids — such as carbon dioxide — to drugs at high pressures. Supercritical fluids cannot exist in liquid or gas form above certain temperatures. As they pass through a solvent, supercritical fluids cause supersaturation and the homogenous precipitation of the desired particles.

The first two techniques employ physical-mechanical force, while micronization capitalizes on fluid energy. 

2. Hot Melt (Fusion)

The hot melt, or fusion, method is another simple and economical technique. While the term is widely associated with hot melt adhesives, the concept behind such products yields a similar effect when applied to pharmaceutical formulation. Two heated components become more than the sum of their parts.

In this technique, a drug mixture and a water-soluble carrier are both subjected to a heating element until they mix. From there, the mixture formed from the two is cooled rapidly in an ice bath while receiving agitation.

This process yields a solid mass ready to be crushed, sieved, combined with a tableting agent and then formed into tablets. For it to work properly, the drug must be sufficiently miscible — it must be able to mix with another substance in any proportion. When performed correctly, this method improves the cycle time compared to other techniques, including spray drying.

3. Ultra-Rapid Freezing

Ultra-rapid freezing (URF) is one of several techniques based on the principles of cryogenics and lyophilization. It involves applying a thin film of a drug compound to a cryogenic substrate —a frozen surface. This process instantly freezes the drug.

During URF, the drug undergoes lyophilization. This part of the freeze-drying method involves removing water and solvent from the drug compound using a vacuum, changing them from their solid forms directly into their gaseous forms without first becoming a liquid.

The result is nanostructured powdered particles of the desired drug compound, each with improved surface area and high bioavailability.

4. Nanosuspension

Nanosuspension offers efficient delivery of especially hydrophobic and oleophobic drug compounds — drugs that are poorly soluble in both water and oil. Without nanosuspension, the resulting drug would have very low bioavailability and would not achieve the desired medical effect.

The process relies on surfactants. When dissolved in water, surfactants displace air on the surface of powders and particles and allow them to disperse more evenly within a liquid carrier. Surfactants stabilize and homogenize nanosized particles of topical or oral drug compounds within a carrier that they would normally not mix well with.

More than 40% of new chemical entities (NCEs) in drug discovery today are insoluble in water. However, nanosuspension using surfactants allows research and development on these difficult compounds to move forward. 

The Key to Consistency and Effectiveness

This list of available techniques is not exhaustive, and some may be used in conjunction with others. Improving drug solubility is key for reducing the number of dosages required by the patient and ensuring consistent performance of the drug in each case — whether the drug is intended for use in capsules, liquids or immediate- or timed-release formulations.

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