Degrees of order: A comparison of nanocrystal and amorphous solids for poorly soluble drugs

Abstract

Poor aqueous solubility is currently a prevalent issue in the development of small molecule pharmaceuticals. Several methods are possible for improving the solubility, dissolution rate and bioavailability of Biopharmaceutics Classification System (BCS) class II and class IV drugs. Two solid state approaches, which rely on reductions in order, and can theoretically be applied to all molecules without any specific chemical prerequisites (compared with e.g. ionizable or co-former groups, or sufficient lipophilicity), are the use of the amorphous form and nanocrystals. Research involving these two approaches is relatively extensive and commercial products are now available based on these technologies. Nevertheless, their formulation remains more challenging than with conventional dosage forms. This article describes these two technologies from both theoretical and practical perspectives by briefly discussing the physicochemical backgrounds behind these approaches, as well as the resulting practical implications, both positive and negative. Case studies demonstrating the benefits and challenges of these two techniques are presented.

Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach

“…Reflection intensity changes for DK-I-60-3 crystals in coarse powder and S5 could be ascribed to preferential orientation difference of DK-I-60-3 crystals (prismatic to needle-like, Figure 1 a) in two samples. The milling process reduced average crystallite size and induced crystal defects concentration increase in F5, which is typical for nanocrystals [ 25 ]. Consequently, with prolonged milling and reduced particle size, the reflections on XRPD diagrams were broadened [ 26 ].…”

Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

“…The use of solid dispersions has been documented as a means to enhance transdermal drug penetration [200,[234][235][236][237]. The mechanism of permeation enhancement employed by ASDs is functionally identical to that employed by nanocrystals [229,235,236].…”

“…The use of solid dispersions has been documented as a means to enhance transdermal drug penetration [200,[234][235][236][237]. The mechanism of permeation enhancement employed by ASDs is functionally identical to that employed by nanocrystals [229,235,236]. The muchimproved dissolution rate of ASDs creates a supersaturated solution atop the skin, which results in a concentration gradient that is the driving force of drug penetration.…”

Numerical modelling of the dissolution of drug nanocrystals and its application to industrial product development

“…Solid-state characterization of nanocrystals Nanocrystals can be seen as an intermediate step in the continuum between perfectly crystalline materials and amorphous phases, where defects and surface features of the crystalline structure can no longer be ignored when describing the solid state of the particles [82].…”

“…In the last three decades, nanocrystals have emerged as a formulation strategy to improve bioavailabilityrelated problems of poorly-soluble drugs, enhance clinical convenience, and enable specific therapeutic benefits [1][2][3][4][5][6][7]. Until now, several commercialized nanocrystalline drug products reached the market for oral, ocular and injection (sc, im, iv) routes of administration [8][9][10]. Beyond that, a small number of nanocrystalline drug products are continuously approaching early development and the generic product lifecycle [9].…”