Particle engineering in pharmaceutical solids processing: surface energy considerations

Abstract

During the past 10 years particle engineering in the pharmaceutical industry has become a topic of increasing importance. Engineers and pharmacists need to understand and control a range of key unit manufacturing operations such as milling, granulation, crystallisation, powder mixing and dry powder inhaled drugs which can be very challenging. It has now become very clear that in many of these particle processing operations, the surface energy of the starting, intermediate or final products is a key factor in understanding the processing operation and or the final product performance. This review will consider the surface energy and surface energy heterogeneity of crystalline solids, methods for the measurement of surface energy, effects of milling on powder surface energy, adhesion and cohesion on powder mixtures, crystal habits and surface energy, surface energy and powder granulation processes, performance of DPI systems and finally crystallisation conditions and surface energy. This review will conclude that the importance of surface energy as a significant factor in understanding the performance of many particulate pharmaceutical products and processes has now been clearly established. It is still nevertheless, work in progress both in terms of development of methods and establishing the limits for when surface energy is the key variable of relevance.

Fig. (1)

Sessile drop contact angle schematic for a liquid droplet on a solid substrate with adsorbed vapor film.

Fig. (2)

Morphine sulfate wetting rates as a function of the surface tension of wetting liquids [6].

Fig. (3)

Series of chromatograms obtained for alkane vapour species interacting with a GC column packed with crystalline fibres.

Fig. (4)

Schematic diagram of the experimental method for determining the distribution profile for ${\mathrm{\gamma }}_S^d$ [32].

Fig. (5)

Macroscopic crystals of β d-mannitol grown from aqueous solution [46].

Fig. (6)

${\mathrm{\gamma }}_S^d$and $\mathrm{\Delta }{G}_{AB}^0$(ethanol) distributions for untreated and silanised d-mannitol [46].

Fig. (7)

${\mathrm{\gamma }}_S^d$ distributions of d-mannitol obtained with different sieve sizes [47].

Fig. (8)

${\mathrm{\gamma }}_S^d$ surface energy heterogeneity distributions measured for 
d-mannitol [58].

Fig. (9)

Cumulative granule size distribution of d-mannitol formulations and the Young’s compressive moduli for single 1mm diameter granules for increasing degrees of powder mixture hydrophobicity [58].

Fig. (10)

Diagrams representing the fracture scenarios of d-mannitol with a needle morphology: (a) fracture direction across (011) and (b) fracture direction across (010) [62].

Fig. (11)

${\mathrm{\gamma }}_S^d$ profiles of milled d-mannitol sieve fractions as a function of bounding rectangular aspect ratios and ${\mathrm{\gamma }}_S^d$, obtained by ‘area under curve’ method, for milled d-mannitol sieve fractions [62].

Fig. (12)

The relationship between crystallinity and K_D/K_A ratios for cefditoren pivoxil [71].

Fig. (13)

Surface energy of wet milled succinic acid and sucrose [73].

Fig. (14)

${\mathrm{\gamma }}_S^d$ surface energy distributions, SBS-Mgst co-milled [76].

Fig. (15)

${\mathrm{\gamma }}_S^d$ distributions for Lactose (Ptos) before and after Ptos mechanofused with 0.1%, 1%, 2%, 5% and 8% magnesium stearate (MgSt) [80].

Fig. (16)

The relationship between the Angle of Repose and surfaces basicity/acidity. The more basic the aluminum powders, lower the angle of repose which correlated to better flowability [83].

Fig. (17)

${\mathrm{\gamma }}_S^d$profiles of three different IMC samples; crystalline, ball milled and melt quenched [84].

Fig. (18)

${\mathrm{\gamma }}_S^d$distributions for crystalline, milled and recrystallised lactose powders [85].