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Article / Mar 03, 2021

Improving Bioavailability & Solubility: Each Molecule Is Unique

  • João Henriques
Drug Development & Delivery, March 20, 2021


SPECIAL FEATURE – Improving Bioavailability & Solubility: Each Molecule Is Unique


The virtual 2020 Global Drug Bioavailability Enhancement Summit this past December showcased novel technologies and platforms aimed at addressing bioavailability and solubility challenges. These included techniques like elec­trospinning, mesoporous silica technology, physiochemical optimization, amorphous nanoparticle engineering, and pharmacokinetic modeling. And the end goal is the same: Save time and money while accelerating formulation devel­opment.


This annual Drug Development & Delivery report introduces readers to some novel approaches to improving bioavailability and solubility that have one commonality: they treat each molecule as unique.


Hovione: Emerging Platforms Address Extreme Compounds

The industry has a wide toolbox to address bioavailability and solubility issues. Promising technologies may require more time and studies, but provide the opportunity to deliver compounds that would be considered unviable in the recent past.

Multiple platforms have emerged in pharmaceutical development to ad­dress bioavailability and solubility challenges. Amorphous solid disper­sions by spray drying have become an industry standard, says João Henriques, Scientist, Group Leader, Hov­ione, R&D Drug Product Development. “This growth is generating a wealth of data that not only provides confidence in the platform, but also creates the foundation for empirical driven for­mulation approaches,” he says. “The use of prior data allows correlating molecular descriptors of low solubility molecules with formulations that have been successfully developed as solid dispersions. The correlations aid in preliminary prototype definition and evaluating of the likelihood of success of such a formulation approach.”

In addition to statistical methods, the use of first-principle models that incorporate thermodynamics of mix­ing, diffusion, and kinetics of solvent evaporation provide valuable infor­mation for in silico screening and ex­cluding non-viable formulations. “Both strategies have their advantages and disadvantages and can be used complementary to each other as a valuable tool for formulators to define the best prototypes to screen and re­duce development time and material consumption while delivering opti­mized formulations that provide the required performance, are stable, and commercially viable,” he explains.

While the formulation of most DCS2b compounds is presently a well-known and understood challenge, there remains a wide space for solu­tions to address some extreme com­pounds that either require significant amounts of stabilizers to maintain the amorphous form or that are not amenable to spray drying with reasonable cost of goods due to low sol­ubility in organic solvents, he states. Alternative production methods of solid dispersions, such as co-precipi­tation, can address the low organic solubility issue. “Emerging platforms, such as impregnation with meso­porous silica, present an opportunity for molecules that cannot be stabilized in the amorphous form with common stabilizers at reasonable ratios,” says Mr. Henriques. “API-loaded silica has been shown to improve amorphous stability of compounds with a high tendency to recrystallize. Additional studies and clinical programs may help establish this technique as a stan­dard alongside lipid formulations and solid dispersions in improving bioavailability and solubility.”

“One of the recurrent challenges we face is related to accelerated ap­provals from the FDA with Fast Track and Breakthrough designations on low solubility compounds,” says Mr. Henriques. “This is common for oncol­ogy programs that show promising early-stage results and may have re­duced clinical study requirements.”

Accelerated approvals put an in­creased amount of pressure on all Chemistry, Manufacturing, and Con­trol (CMC) activities, which must be compressed and de-risked, he says. The use of enabled formulations fur­ther increases the complexity of this activity. “Adequate risk assessment and management tools are required because reformulations may compro­mise all clinical timelines,” says Mr. Henriques. “Right-first-time formula­tion in this case is a significant advan­tage, and all formulation activities must have a strong sense of the man­ufacturability and scalability early to ensure seamless transition from clini­cal to commercial scales.”


Read the full article on the Drug Development & Delivery website