Excipients That Facilitate Amorphous Drug Stabilization

Abstract

The importance of the amorphous state in studying bioavailability of poorly water-soluble drugs cannot be over-emphasized. The higher free energy and therefore the apparent high solubility of the amorphous phase are some of the advantages for promoting the amorphous phase, as compared to its crystalline counterpart. It is well known that the amorphous phase is thermodynamically unstable. This might result in the conversion of the metastable form to its stable crystalline form during storage. This conversion might also lead to product failure during storage owing to the poor dissolution properties of the crystalline form. Excipients can play a key role in preventing such a transformation during storage as well as maximizing the therapeutic efficacy of the amorphous material. This book chapter intends to highlight the delivery issues pertaining to amorphous drugs with a special emphasis on the most commonly used excipients in stabilizing amorphous drug substances in formulations.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles

“…The stabilizers adsorbed on the nanoparticles surface during the FNP process can decrease particle size significantly by reducing the interfacial energy at solid-liquid interface and increasing the nucleation rate 40 , 64 . On the other hand, it also can provide a long-term stability by limiting the Ostwald ripening 65 , crystal form transformation 66 , 67 and nanoparticle agglomeration 68 , 69 .…”

“…Because of the solubility of the metastable crystal is higher than that of the stable crystal, the difference of the solubility of the different crystal forms is the driving force of the crystalline transformation. Therefore, many studiers used suitable excipients 66 , 67 and combined with freeze-drying or spray-drying by removing water medium to stabilize the drug nanoparticles as amorphous 61 , 62 , 63 , 97 , 98 , 104 , 105 , 106 , 108 , 112 .…”

“…Actually, the surfactants often combined with polymeric stabilizers to enhance the drug nanoparticle stabilization through synergistic effect. The studies found that the combination of HPMC with SDS was more effective for drug nanoparticle stabilization than HPMC alone or HPMC–Tween 80 combination38, 66 because the ionic surfactant SDS offered the electrostatic repulsion and HPMC offered the steric protection to the drug particles. On the other hand, the surface properties of the nanoparticles were also largely determined by the stabilizers, such as zeta potential, morphology 69 , long circulation 77 , and cellular uptake ability 78 .…”