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By Rutesh Dave and Rohit Dugar

Rutesh Dave - final Rohit Dugar - finalFor decades the pharmaceutical industry has been facing a flood of active pharmaceutical ingredients (APIs) that have poor aqueous solubility. These APIs we commonly call BCS class II drugs, and their most important aspect is solubility in the appropriate body fluids. It is a prerequisite for a drug to show its pharmacological effect. Solid oral dosage forms are one of the most common and frequently used delivery routes for pharmaceutical applications. For these formulations, it is very critical that the drug solubilizes in the gastrointestinal fluid and remains solubilized until it gets absorbed into the bloodstream. If the drug precipitates before getting absorbed, it probably gets excreted unchanged and its effect is diminished. So there are two major concepts that need to be taken into consideration:

  • How much drug is solubilized?
  • How long does it remain solubilized?

Tremendous efforts have been made by pharmaceutical scientists to overcome this poor aqueous solubility. Numerous technologies have been developed and are being developed each year in an attempt to overcome this major challenge. Techniques such as amorphous solid dispersions, nanotechnology, salt formation, use of hydrophilic excipients, eutectic systems, liposomal drug delivery, and many others are currently being used. Many studies have explored their potential in drug solubility enhancement. Scientists have achieved success in increasing solubility by mastering the above techniques. However, the problems of dose dumping, reduced biological activity, batch to batch variations, and so forth are still a challenge during drug product development.

All the above techniques take a deep dive into the amount of drug solubility enhancement and the underlying mechanisms. But equal thought should also be given to the second concern—the postsolubilization one—how long it remains in solution in the desired fluids. Because of this phenomenon, we observe the spring and parachute effect in the dissolution profiles of these drugs. The spring here is the dissolution enhancement or boost in percent of dissolved drug due to increased solubility using the above techniques, and the parachute is the decrease in dissolved drug over time due to its inability to remain solubilized. In our recent publication in AAPS PharmSciTech, we encountered this phenomenon and saw how the formation of micelles could help in keeping the drug remain solubilized for a prolonged period of time as compared to the drug as seen in the figure.

Spring&Parachute

More studies are surely needed to fully understand the concept of the spring and parachute effect, which would help us develop formulations that can kill the above two birds with one stone.

Rohit Dugar is a Ph.D. candidate at Long Island University, NY, currently conducting research at the Natoli Institute for Industrial Pharmacy at LIU.
Rutesh Dave, Ph.D., is currently division director of Pharmaceutical Sciences at Arnold and Marie Schwartz College of Pharmacy and Health Sciences at Long Island University. His current interests are in the field of preformulation, formulation and drug delivery.