Simultaneous particulate design of primary and agglomerated crystals of steroid by spherical agglomeration in liquid for dry powder inhalation

Engineering of Piroxicam Agglomerates by Additives Using Wet Agglomeration Technique

“…It has been shown that two factors play important role in the compressive strength of the agglomerates: loading the crystals compactly in the agglomerates and creation of solid bridges between the primary crystals. 12 Results showed (Figure 1) that adding surfactant to the binder liquid made a significant difference in the friability of the prepared agglomerates (P< 0.05) in the manner that by increasing in the concentration of this additive in binder liquid the agglomerates were able to resist the shear rate more strongly. Physically powerful structure of these agglomerates may be related to positive effect of surfactant on the wetting step of agglomeration procedure.…”

“…9,10 In spite of many advantages of this method, it is still not widely used in industry because the mechanisms of this technique have not been fully clarified. Some studies dealing with wet agglomeration were carried out to assess the effect of agglomeration variables such as stirring speed, temperature of operation, 11 amount of binder liquid and injection means, 12 the crystal size on the properties of the prepared agglomerates. 13 However, lack of complete understanding the effect of method variables on the agglomerates properties lead to difficulties in managing the procedure that let making of agglomerates with preferred properties.…”

Particle Engineering Strategies via Crystallization for Pulmonary Drug Delivery

“…71,72 The agglomerated crystals could deagglomerate readily into primary particles upon mixing with lactose carrier for 2 min or more, and the adhered primary crystals can easily detach from the lactose during inhalation with substantial enhancement in inhalation efficiency, i.e., 2-3 times higher FPF compared with micrometerized materials. [71][72][73][74] Spherical crystallization can also be achieved for certain drug materials by quenching of a hot organic or aqueous organic solution of the drug with a cold organic or aqueous organic solvent. The quench solvent should be miscible with the drug solvent.…”

Agglomerative crystallization of ABT‐510 in a partially miscible solvent system

“…[9][10][11] All these techniques have features that limit applicability; for instance QESD and wet agglomeration based procedures require identification of effective emulsifying and wetting agents respectively that are not trapped at levels adversely affecting purity of the API. LLPS based procedures require very high levels of super-saturation to induce phase separation and could lead to nucleation of meta-stable solids phases, thereby potentially limiting application to systems that do not exhibit polymorphism.…”

“…Agglomeration techniques pertinent to molecular crystals can be classified into three general categories, i.e., quasi-emulsion solvent diffusion (QESD) based techniques, 5,6 liquid-liquid phase separation (LLPS) based techniques 7,8 and wet agglomeration techniques. [9][10][11] All these techniques have features that limit applicability; for instance QESD and wet agglomeration based procedures require identification of effective emulsifying and wetting agents respectively that are not trapped at levels adversely affecting purity of the API. LLPS based procedures require very high levels of super-saturation to induce phase separation and could lead to nucleation of meta-stable solids phases, thereby potentially limiting application to systems that do not exhibit polymorphism.…”