461274 Comparison of the Electrostatic Properties of Amorphous and Crystalline Lactose

Sunday, November 13, 2016: 4:08 PM
Peninsula (Hotel Nikko San Francisco)
Karolina Biegaj1, Tim Lukas2, Martin Rowland2 and Jerry Heng1, (1)Department of Chemical Engineering, Imperial College London, London, United Kingdom, (2)Pfizer Pharmaceutical Sciences, Sandwich, United Kingdom


Conversion from a crystalline to amorphous state in solid materials may be observed as a result of various processes applied to pharmaceutical materials during manufacturing. Examples include rapid crystallisation from solution to mechanical activation of the crystalline phase upon milling.1-2 The resulting products usually display different thermodynamic properties to pure crystalline forms, hence affecting their subsequent performance.2-3 Furthermore, powders are susceptible to a process called tribocharging whenever movement of particles across the surface is involved. If surface amorphization is observed during processes involving the movement of powder, such as during milling, generation and accumulation of electrostatic charge could be affected significantly, hence affecting the overall powder flow and sticking.


The aim of this work is to determine how the presence of an amorphous state influences the electrostatic performance of lactose. The main objectives involve determining whether the material electrostatic characteristics such as the maximum charge accumulated and charge decay behaviour are directly dictated by the material’s state.


Amorphous lactose was prepared by spray drying from water and storing at dry conditions to limit its re-crystallisation. The electrostatic properties of both pure crystalline and pure amorphous lactose with known particle size were studied using JCI 155v6 Charge Decay Analyser4 under controlled environmental conditions (25 °C and 25% RH). Subsequently, four blends containing 15%, 30%, 50% and 75% amorphous content by mass were prepared and characterised using the same method. All samples studied were further characterised using PXRD, RST and SEM. The analysis for further applied to anhydrous lactose prepared by dehydration of crystalline lactose by exposing to elevated temperatures.


Electrostatic characterisation of pure amorphous and crystalline lactose revealed that the materials showed significantly different behaviour in terms of maximum charge accumulated as a result of corona charging and decay characteristics. The maximum charge of -684.65 ± 45.04 V/g acquired by the pure amorphous lactose was twice as large as the charge accumulated by the pure crystalline sample (-337.64 ± 5.56 V/g). Although the smaller particle size of amorphous lactose could potentially account for its greater overall charge accumulation, the decay profiles are significantly different for the two forms with the amorphous lactose showing significantly slower charge decay. The time of 113.19 ± 8.30 min is required for the charge on the amorphous lactose to decay to 10% of its initial value, whereas only 10.03 ± 0.16 min is needed for the crystalline sample to reach the same level. Results obtained for four blends with varied amorphous content show that the material performance is directly dictated by its composition and a linear correlation was obtained between charge accumulated and amorphous content of the blends. The same correlation was observed for the charge decay profiles.


The results obtained show that amorphous lactose is able to accumulate a larger amount of electrostatic charge, which is retained for a prolonged time compared to its crystalline form. This behaviour is then directly translated into lactose blends having varied amorphous content, where both components exist in a form of physical mixture. Even though amorphous lactose is unstable and tends to convert to crystalline form quite rapidly, its generation during processing could lead to significant charge generation and accumulation that otherwise would not be expected for a crystalline material.


The authors acknowledge Dr Jin Wang Kwek for his contribution to this work.


(1) Descamps, M.; Willart, J. F.; Dudognon, E.; Caron, V., Transformation of pharmaceutical compounds upon milling and comilling: the role of T(g). J. Pharm. Sci. 2007, 96 (5), 1398-1407.

(2) Hancock, B. C.; Zografi, G., Characteristics and significance of amorphous states in pharmaceutical systems. J. Pharm. Sci. 1997, 86 (1), 1-12.

(3) Fitzpatrick, J. J.; Hodnett, M.; Twomey, M.; Cerqueira, P. S. M.; O'Flynn, J.; Roos, Y. H., Glass transition and the flowability and caking of powders containing amorphous lactose. Powder Technol. 2007, 178 (2), 119-128.

(4) Rowland, M. G. Electrostatic Properties of Particles for Inhalation. University of Bath, 2014.

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