Amorphous Pharmaceuticals

Three amorphous materials casting colorful reflections against a black background.

A large fraction of new active ingredients suffers from the problem of low aqueous solubility. Drug amorphization is a promising approach to enhance the apparent solubility and consequently the oral bioavailability of such actives. The amorphous form improves the aqueous solubility by orders of magnitude, but possesses low physical instability in comparison to its crystalline counterpart. As a result, the development of robust pharmaceutical products containing an amorphous active is challenging, owing to the high propensity of amorphous materials to transform to the corresponding crystalline state. This requires deeper understanding of 1) the involved phase transformation; 2) its impact on the pharmaceutical performance of the product; 3) the impact of other formulation components (including polymers); and 4) the impact of the processing parameters. We have been actively involved in developing molecular understanding of such systems with an objective of enabling the development of robust pharmaceutical products containing amorphous actives.

Further Reading

  1. K.K. Amponsah-Efah, P. Mistry, R. Eisenhart, R. Suryanarayanan. The Influence of the Strength of Drug-Polymer Interactions on the Dissolution of Amorphous Solid Dispersions. Mol Pharm, 18(1), 174-186 (2020).
  2. A. Sahoo, R. Suryanarayanan, R.A. Siegel. Stabilization of Amorphous Drugs by Polymers: The Role of Overlap Concentration (C*). Mol Pharm, 17(11), 4401-4406 (2020).
  3. M.H. Fung, K. Be̅rziņš, R. Suryanarayanan. Physical stability and dissolution behavior of ketoconazole–organic acid coamorphous systems. Mol Pharm, 15(5), 1862-1869 (2018).
  4. M.H. Fung, M. DeVault, K.T. Kuwata, R. Suryanarayanan. Drug-excipient interactions: effect on molecular mobility and physical stability of ketoconazole–organic acid coamorphous systems. Mol Pharm, 15(3), 1052-1061 (2018).
  5. S. Thakral, M.W. Terban, N.K. Thakral, R. Suryanarayanan. Recent advances in the characterization of amorphous pharmaceuticals by X-ray diffractometry. Adv Drug Deliv Rev, 100, 183-193 (2016).
  6. M. Mehta, G.B. McKenna, R. Suryanarayanan. Molecular mobility in glassy dispersions. J Chem Phys, 144(20), 204506 (2016).
  7. S. Bhattacharya, R. Suryanarayanan. Local mobility in amorphous pharmaceuticals - characterization and implications on stability. J Pharm Sci, 98(9), 2935-2953 (2009).
  8. K. Kothari, V. Ragoonanan, R. Suryanarayanan. The role of drug-polymer hydrogen bonding interactions on the molecular mobility and physical stability of nifedipine solid dispersions. Mol Pharm, 12(1), 162-170 (2014).