Supersaturation–Nucleation Behavior of Poorly Soluble Drugs and its Impact on the Oral Absorption of Drugs in Thermodynamically High-Energy Forms

Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways

“…In solid-to-solid transformation, the increase in temperature or water sorption increases the molecular mobility of the amorphous system which may lead to an increase in the crystallization rate [6]. In contrast solution-mediated crystallization requires a supersaturated solution [6], [7], [8], [9]. Both solid-to-solid and solution-mediated transformations start with nucleation in which stable nuclei are formed, followed by crystal growth [6], [7], [8].…”

“…In contrast solution-mediated crystallization requires a supersaturated solution [6], [7], [8], [9]. Both solid-to-solid and solution-mediated transformations start with nucleation in which stable nuclei are formed, followed by crystal growth [6], [7], [8]. The formation of stable nuclei is the rate-limiting step, as it requires overcoming a nucleation barrier, but subsequent crystal growth can be rapid, and is accelerated by increasing temperature [8].…”

“…The crystallization behaviour of amorphous formulations in the solid and dissolved states can be studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapour sorption (DVS), polarized light microscopy (PLM), powder x-ray diffraction (XRPD), Raman spectroscopy, and dissolution assays [7], [8], [11], [12], [13]. Few years ago, Alonzo and co-workers introduced the use of different experimental techniques including XRPD, microscopy, Raman spectroscopy and small-scale dissolution apparatus to study the behaviour of amorphous systems during dissolution [7] and the effect of polymers on their dissolution and precipitation behaviour [14].…”

Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures

“…10 Supersaturatable dosage forms improve the solubility and oral bioavailability of water-insoluble drugs, and are now being widely explored in the pharmaceutical industry. [11][12][13][14][15] Amorphous solid dispersion and lipid-based formulations (eg, the supersaturatable self-microemulsifying drug delivery system) containing polymeric precipitation inhibitors are regarded as supersaturatable formulations. The supersaturated state is a thermodynamically unstable amorphous form and eventually reverts to a stable state because of drug precipitation.…”

Preparation and Evaluation of Solid Dispersion of Atorvastatin Calcium with Soluplus® by Spray Drying Technique

“…In many cases, this improves the solubility and dissolution of the API compared to the crystalline material, since an amorphous form may lead to higher levels of supersaturation. 2,3) Consequently, amorphous solid dispersion has become an increasingly utilized approach for improving the bioavailability of poorly water-soluble compounds. [4][5][6][7] In many cases, a supersaturated drug solution generated by amorphous solid dispersion is thermodynamically unstable and energetically tends to return to equilibrium via precipitation.…”