Triboelectrification of Active Pharmaceutical Ingredients: Amines and Their Hydrochloride Salts

Abstract

The triboelectric properties of active pharmaceutical ingredients (APIs) contribute to problems during the manufacturing of pharmaceuticals. However, the triboelectric properties of APIs have not been comprehensively characterized. In this study, the effect of salt formulation on the triboelectric properties of APIs was investigated. The triboelectric properties of three groups of amines, namely tertiary amines, purine bases, and amino acids, and their hydrochlorides were evaluated using a suction-type Faraday cage meter. Most of the hydrochloride salts exhibited more negative charges than the corresponding free bases, and the degree by which the triboelectric property changed upon hydrochlorination depended on the structural groups of the compounds. In the case of tertiary amines, the change in the zero-charge margin upon hydrochlorination was negatively correlated with the zero-charge margin of the free base. In contrast, hydrochlorination of the amino acids led to a significant change in the zero-charge margin. In most cases, salt formation also affected the triboelectric properties of API powders. Controlling the triboelectric properties of APIs solves various problems caused by the electrification of raw material powders and granules during the production of pharmaceuticals, thereby increasing the quality of produced pharmaceuticals.

Introduction

Solid-state physicochemical properties of active pharmaceutical ingredients (APIs) and excipients are characterized during drug development. A drug can be developed with APIs in various forms, such as salts, co-crystals, amorphous forms, and crystal polymorphs.¹⁾ Solid form of API affects various properties of the drug, such as dissolution,²⁾ chemical stability,³⁾ and physical stability.⁴⁾ Techniques commonly employed to characterize solid forms of APIs include powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and solid-state nuclear magnetic resonance spectroscopy. Morphological features of the powder, such as particle size, particle shape, and specific surface area, are also evaluated. Triboelectric properties of prescription components, such as APIs and additives, are empirically known to significantly influence manufacturing and quality of pharmaceutical products. Triboelectrification often occurs when APIs and excipients contact other materials, such as excipients, storage vessels, and production equipments.^5–7) This phenomenon affects powder flowability,^8,9) dosage uniformity,^10,11) and metal sticking,^12,13) among other properties. Specifically, in a fluidized bed granulation process, components are separated in a granulation container due to electrostatic repulsion, reducing uniformity of the granulated powder.¹⁴⁾ Only a certain component may adhere to the inner wall of granulation container, resulting in increase or decrease in API content.⁶⁾ Alternatively, only certain components may aggregate in the mixing and granulation process, reducing the uniformity of the tablet powder.^15,16) The above-mentioned troubles are thought to affect the quality of the preparation, especially the content uniformity and dissolution properties. Therefore, understanding the triboelectric properties of APIs is critical in designing manufacturing processes for solid pharmaceutical products.^17–19) Despite the importance of evaluating the triboelectric properties, the number of reports on the triboelectric properties of APIs and excipients is limited.^5–7) It has been reported that nitrogen-containing polymer particles with high electron densities surrounding electron-donating groups tend to be positively charged through triboelectrification, while those with low electron densities surrounding electron-withdrawing groups tend to be negatively charged.²⁰⁾ Similar to polymers, the triboelectric properties of API particles can be influenced by the chemical structure of API. However, the relationship between the chemical structure and triboelectric properties of APIs is not well understood. Because the API contents in most pharmaceutical formulations are low, even a small amount of API adhesions to the manufacturing equipment can reduce the API contents in the formulations and even a small amount of API particle aggregation can reduce the uniformities of the API contents. One of the main causes of these quality reductions is the triboelectric properties of API. Therefore, this study focused on evaluating the triboelectric properties of the API.

The triboelectric properties of powder have been extensively investigated for the manufacturing of other industrial products, such as toner inks and paintwork powder. The triboelectric properties of powder have been quantitatively evaluated using methods employing impact charging and particle motion analysis.²¹⁾ In our previous study, we employed the blow-off method with standard carrier beads from the Imaging Society of Japan to evaluate the triboelectric properties of API powder.²²⁾ In this method, a sample is forcibly charged by four types of standard carrier beads with different charges, and the specific charge (μC/g) is measured. The blow-off method introduces a new evaluation index, called the zero-charge margin.²²⁾ The zero-charge margin is calculated from the specific charge of sample charged with four standard carrier beads. In conventional evaluation methods, the measured value of charge is significantly affected by humidity at the time of measurement, and thus it is necessary to strictly control humidity during the measurement. In contrast, the zero-charge margin method is less affected by humidity because it uses standard carrier beads to forcibly charge the sample, and thus it does not require the strict humidity control enforced for other test methods.²²⁾ Because the effect of measurement conditions, such as humidity, is minimal, the blow-off method provides the specific charge of powder samples with higher accuracy and reproducibility than other methods and is expedient for determining the triboelectric properties of many samples. Additionally, evaluation based on zero-charge margin cannot assume frictional electrification when coming into contact with constituent materials such as stainless steel and other pharmaceutical manufacturing equipment.²³⁾ On the other hand, zero-charge margin can be used to evaluate and compare the unique charging characteristics of powders such as pharmaceutical raw materials. Using this method, we found that crystalline powder of APIs with free carboxylic acids exhibit more positive charges than those of their sodium salts.²²⁾ This suggests that counterions of API salt crystals may be one of the key factors that determine the triboelectric properties of API powder. However, details of the effects of counterions on triboelectric properties remain unknown. The purpose of this study was to investigate the effect of hydrochloride salt formation on the triboelectric properties of various APIs with amine groups.

Results and Discussion

Evaluation of Zero-Charge Margin

The zero-charge margins of powder samples are shown in Fig. 1. The zero-charge margins of all tertiary amine free bases investigated (procaine, chlorpromazine, fexofenadine, lidocaine, promethazine, and flavoxate) were negative, indicating that they exhibited positive chargeability (Fig. 1). The most charged tertiary amine, flavoxate, had a zero-charge margin of −77.9 ± 6.2 µC/g, whereas the least charged tertiary amine, procaine, had a zero-charge margin of −34.7 ± 1.5 µC/g. The zero-charge margins shifted to positive values upon hydrochlorination of tertiary amines except procaine. The positive shifts of the zero-charge margins were largest for the free bases of lidocaine and flavoxate, whose absolute zero-charge margins were large, and smallest for the free bases of fexofenadine and promethazine, whose absolute zero-charge margins were small. Procaine, which had the lowest absolute zero-charge margin, showed a slight increase in the absolute zero-charge margin after hydrochlorination. All tertiary amine hydrochlorides had similar zero-charge margins, and the average of the zero-charge margins of the hydrochloride salts of the tertiary amines was −43.4 ± 3.4 µC/g. For each of the tertiary amine hydrochloride salts except for flavoxate hydrochloride whose crystal structure is unknown, a negative correlation was observed between the change in the zero-charge margins upon hydrochlorination and the distances between the nitrogen atoms and the chloride ions (Fig. 2). It is expected that when the cationized nitrogen atom is located closer to the chloride ion, the chloride ion may stabilize the positive charge of the nitrogen atom, which would then attract electrons more strongly during the triboelectric charging. On the other hand, it is possible that the chloride ions repel electrons, making them more positively charged. Because the ionic radius of the cationized nitrogen atom is smaller than that of the chloride ion, the cationized nitrogen ions may be able to attract electrons closer to them. Therefore, the influence of the cationized nitrogen atoms which attract electrons would be stronger than that of the chloride ions which repel electrons. In the crystal of procaine hydrochloride, the distance between the cationized nitrogen atom and the chloride ion was longest among the tertiary amines, and the positive charge of the cationized nitrogen atom is less susceptible to stabilization by chloride ions, making the positive charge less stable. This might explain why the zero-charge margin of procaine hydrochloride changed slightly negative.

Fig. 1. Zero-Charge Margins of Free Bases and Their Hydrochloride Salts

Fig. 2. Plot of the Distance between the Nitrogen Atom and Chloride Ion in the Crystal and the Change in the Zero-Charge Margin upon Hydrochlorination in a Tertiary Amine

The absolute values of the zero-charge margins of the purine bases, adenine and guanine, were small (Fig. 1). The zero-charge margin of the more charged purine base, guanine, was 8.3 ± 3.3 µC/g, while the zero-charge margin of the less charged purine base, adenine, was −1.4 ± 1.0 µC/g. Hydrochlorination of both purine bases positively shifted the zero-charge margin.

The zero-charge margins of glycine, L-cystine, and amino acids with basic side chains, L-arginine, and L-histidine, were negative (positive chargeability), whereas those of amino acids with acidic side chains, L-glutamic acid and L-cysteine, were positive (negative chargeability) (Fig. 1). The zero-charge margin of the most positively charged amino acid, L-arginine, was −53.0 ± 5.8 µC/g, and that of the most negatively charged amino acid, L-cysteine, was 15.4 ± 1.6 µC/g. Hydrochlorination of the amino acids positively shifted the zero-charge margins, as with most of the tertiary amines and both purine bases. The differences between the zero-charge margins of free bases and hydrochloride salts of the amino acids (28.2–85.1 µC/g) were larger than those of the tertiary amines (3.6–32.9 µC/g) and the purine bases (9.6–14.8 µC/g). L-Arginine, the free base with the largest negative zero-charge margin among the amino acid samples, retained the negative zero-charge margin even after hydrochlorination. Similarly, L-cysteine, the free base with the largest positive zero-charge margin among the amino acid samples, had the largest positive zero-charge margin even after hydrochlorination. In contrast to the comparable zero-charge margins of the tertiary amine hydrochlorides, the zero-charge margins of the amino acid hydrochlorides varied widely. In addition, the acid dissociation constants pK_a of the amino groups of α-amino acids and the changes in the zero-charge margin upon conversions to hydrochloride salts were compared. Glycine (pK_a = 9.9²⁴⁾) and L-cysteine (pK_a = 10.6²⁵⁾), which have larger positive shift in zero-charge margin, were found to have larger pK_a than the other amino acids (pK_a = 8.1–9.5^25–28)). Therefore, it was thought that amino acids with highly basic amino groups bonded to the α-carbon atoms would have more stable positive charges on the cationized nitrogen atoms when converted to hydrochloride salts, and would have a greater ability to attract electrons when triboelectrically charged.

Evaluation of Effect of Hydrochlorination on Triboelectric Properties

When a free base is converted to a hydrochloride salt, the nitrogen atom of amine group becomes positively charged through protonation. When the hydrochloride salt receives electrons through triboelectrification, the ionized nitrogen atom attracts and stabilizes the received electrons, making it negatively charged. Therefore, the hydrochloride salt would show more negative chargeability than the corresponding free base powder.

Although the number of samples is small, it is suggested that each group exhibits a certain tendency in triboelectric charging characteristics. All tertiary amines used in this study, including the free base and hydrochloride salt, had negative zero-charge margins. The negative zero-charge margins of the tertiary amine bases might be partly ascribed to the higher basicity of the tertiary amine moieties, which repel the negative charges from triboelectrification. In addition, the tertiary amines used in this study have functional groups with high electronegativities, such as hydroxyl groups, carbonyl oxygens, and chlorine atoms. Therefore, the positive shift of the zero-charge margin upon hydrochlorination of the amine group would be suppressed by repulsion from the negative charges of other highly electronegative functional groups. Consequently, the salt exhibited a negative zero-charge margin, like the free base.

The hydrochloride salts showed larger zero-charge margins, or higher negative chargeability, than their free bases, except in the case of procaine. This correlation was found by plotting the zero-charge margin of the hydrochloride salt against that of the free base for all samples used in this study (Fig. 3). Although the tendency is weak in the tertiary amine group, the regression line of the plot showed a high coefficient of determination, R² = 0.672, and the slope and the intercept on the vertical axis had positive values. Furthermore, to examine the change in the triboelectric properties in detail, the change in the zero-charge margin upon hydrochlorination was plotted against the zero-charge margin of the free base (Fig. 4). In the case of tertiary amines used in this study, the changes in the zero-charge margins upon hydrochlorination were negatively correlated with the zero-charge margins of the free bases (R² = 0.970). In the tertiary amine group, the more negative the zero-charge margin of the free base, the more positive the zero-charge margin changed when converted into hydrochloride. This indicated that the zero-charge margins of the hydrochloride salts were comparable, regardless of the zero-charge margins of their free bases. Although it was not possible to evaluate the correlation as there were only two pieces of data for purine bases, it is possible that the larger the positive zero-charge margin of the free base, the more positive the zero-charge margin will change when converted to hydrochloride. In contrast, the amino acids used in this study showed no correlation between the above parameters, with R² = 0.003. Therefore, the degree by which the triboelectric properties changed upon hydrochlorination of the free bases depended on the chemical structure of the compounds.

Fig. 3. Correlation of the Zero-Charge Margins of Free Bases and Their Hydrochloride Salts

Fig. 4. Plot of the Zero-Charge Margin of the Free Base against the Change in the Zero-Charge Margin upon Hydrochlorination

The zero-charge margins of the amino acids used in this study increased significantly upon hydrochlorination, as evident by the scatter in the upper region of Fig. 4. Amphoteric compounds, such as amino acids, have functional groups with negative (such as carboxyl group²⁹⁾) and positive (such as amine group²⁰⁾) triboelectricity, and functional groups with opposite triboelectricity coexist within the same molecule. When an amino acid is converted into a hydrochloride salt, protonation of the amine group increases the positive charge within the molecule, while protonation of the anionic carboxyl group reduces the negative charge. Therefore, the increase in the negative triboelectricity was attributed to the changed electronic state of the amino acid molecule.

The acid dissociation constant of the amino groups (Supplementary Table 1) and zero-charge margins were compared for each sample (Fig. 5). The larger the dissociation constant of the amino group, the larger the zero-charge margin of the free base (R² = 0.5901). Therefore, the more basic the amino group, the more negatively charged the free base. It was thought that the higher the basicity of the amino group, the more stable the positive charge of the cationized nitrogen atom, and the higher the negative chargeability. On the other hand, the correlation for the hydrochloride salts was very weak (R² = 0.3432). The factors that affect the amount of changes in the triboelectric properties when converted to hydrochloride salts differ for each sample group. For tertiary amines, the amount of changes was affected by the distances between the cationized nitrogen atoms and the chloride ions in the crystals. For amino acids, it was affected by the pK_a of the amino groups of α-amino acids. These may explain why the correlation between the pK_a of the amino group and the triboelectric properties was weaker.

Fig. 5. Plot of the Dissociation Constant of the Amino Group against the Zero-Charge Margin

The ratios of polar for surface free energy to the total surface free energy, the surface polarity ratios (Table 1), and the zero-charge margins were compared (Fig. 6). For the free bases, a correlation was found in which the higher the surface polarity ratios, the lower the zero-charge margins (R² = 0.6955). Therefore, it was thought that the triboelectric properties of the free bases of the amines became more positively charged as the surface polarity increased. On the other hand, the hydrochloride salts showed no correlation between the surface polarity ratios and the zero-charge margins (R² = 0.0009). When the free base is converted to a hydrochloride salt and cationic nitrogen atoms and/or anionic chloride ions might reside near the crystal surface, the cations and the anions increase the polarity of the surface. However, cations attract electrons when triboelectrically charged, while anions repel electrons. This may have led to the lack of correlation between the surface polarity ratios and the triboelectric properties.

Table 1. Surface Free Energy of Each Powder Sample

Type of amine	Sample name	Surface free energy [mJ/m2]		Surface polarity ratio
		γd	γp
Tertiary amines	Procaine	35.08	8.63	0.197
	Procaine hydrochloride	32.78	8.14	0.199
	Chlorpromazine	6.20	16.06	0.721
	Chlorpromazine hydrochloride	19.38	11.44	0.371
	Fexofenadine	8.87	19.28	0.685
	Fexofenadine hydrochloride	2.96	27.08	0.901
	Lidocaine	10.15	39.54	0.796
	Lidocaine hydrochloride	35.24	8.49	0.194
	Promethazine	15.07	19.24	0.561
	Promethazine hydrochloride	29.08	10.23	0.260
	Flavoxate hydrate	3.93	16.47	0.807
	Flavoxate hydrochloride	25.11	10.06	0.286
Purine bases	Adenine	28.64	11.62	0.289
	Adenine hydrochloride	31.59	7.89	0.200
	Guanine	25.40	11.36	0.309
	Guanine hydrochloride	35.48	8.28	0.189
Amino acids	Glycine	20.69	12.94	0.385
	Glycine hydrochloride	16.29	7.35	0.311
	L-Arginine	10.73	59.40	0.847
	L-Arginine hydrochloride	31.17	7.80	0.200
	L-Cystine	35.08	8.63	0.197
	L-Cystine dihydrochloride	4.44	14.43	0.765
	L-Histidine	35.08	8.63	0.197
	L-Histidine dihydrochloride	16.26	10.97	0.403
	L-Glutamic acid	36.79	7.19	0.163
	L-Glutamic acid hydrochloride	6.58	21.80	0.768
	L-Cysteine	33.79	8.95	0.209
	L-Cysteine hydrochloride monohydrate	27.67	6.32	0.186

Fig. 6. Plot of the Surface Polarity Ratio against the Zero-Charge Margin

The necessity of normalization by specific surface area for the obtained zero-charge margin was examined (Supplementary Fig. 1). The normalization had little effect on the relative values of the zero-charge margins, suggesting that the normalization was not necessary in these cases. This is probably because the specific surface area of the samples in this study differed little. If there is a large difference in specific surface area between the samples, the normalization based on the specific surface area may be required.

In our previous study, we found that converting carboxylic acids to sodium salts enhances the positive chargeability of the free acids.²²⁾ In addition, when the functional groups of APIs become negatively ionized from salt formation, the positive triboelectricity is enhanced, and when they become positively ionized, the negative triboelectricity is enhanced. Salt formation through various functional groups other than carboxyl and amine groups, which were investigated in this and previous studies, might also change the triboelectric properties of the compounds. In future, it will be possible to devise methods for controlling the chargeability of each compound for a wider range of compounds by studying various compounds with different structures and different types of counterions. In the manufacturing process of pharmaceuticals, many problems occur due to the charging characteristics of APIs and additives (for example, component separation during fluidized bed granulation and aggregation of specific components during the mixing process). When the above-mentioned problems occur, they can often be resolved by combining prescription ingredients or improving manufacturing methods. However, if the problem cannot be solved by such measures alone, there is a possibility that a breakthrough can be achieved by selecting the salt form. This research shows that it is possible to control the triboelectric properties by changing the solid form of the API, which solves various problems caused by the electrification of raw material powders and granules during the production of pharmaceuticals, thereby enhancing the quality of produced pharmaceuticals.

Conclusion

We found that for many of the amines used in this study, the formation of hydrochloride salts shifts the triboelectric properties toward negative charging. In addition, the change in the triboelectric properties upon hydrochlorination of the free bases differed for each compound groups, with small changes for tertiary amines and purine bases and large changes for amphoteric amino acids. These effects of salt formation on the triboelectric properties suggest that the electrification of raw material powder and granules, which causes various problems during the manufacturing of pharmaceuticals, can be suppressed by appropriately selecting a free or salt form of the drug substance. The present study investigated the free bases and their hydrochloride salts of amines, and further research would be required on the API salt crystals with different counter ions because they might exhibit different behaviors in triboelectrification depending on the counter ion types. Additionally, furthering this research could help select optimal formulation combinations (e.g., more miscible drug substance and excipient combinations) in drug design.

Experimental

Standard Carrier Beads and Standard Toner

Standard carrier beads (N-01, N-02, P-01, and P-02) distributed by the Japan Imaging Association (Tokyo, Japan) were used in this study.^22,23) The carrier beads differ in composition and charge-donating/accepting ability.²²⁾ Standard carrier beads have core particles composed of magnetite and manganese ferrite coated with fluorine acrylic resin for P-02, knitted silicone resin for P-02, silicone resin for N-01, and acrylic resin for N-02. Each standard carrier bead has a unique charge donating/accepting ability derived from the coating agent, which forces the mixing partner to become electrically charged. The particle surface of each standard carrier bead has a uniform structure, making it possible to charge the mixing partner with good reproducibility. The charge-donating/accepting abilities of these standard carrier beads have been standardized by the Japan Imaging Society using standard toners.^22,23) Table 2 shows the particle size distribution of the standard carrier beads and the specific charge of the standard toner when mixed and triboelectrified with each standard carrier bead. The standard toner is most negatively charged when mixed with N-01 and most positively charged when mixed with P-02. In addition, N-02 and P-01 have weaker charge-donating/accepting abilities than N-01 and P-02, respectively.

Table 2. Particle Size Distribution of Standard Carrier Beads and Specific Charge of the Standard Toner Triboelectrified with Each Standard Carrier Bead

	Grade of standard carrier beads
	N-01	N-02	P-01	P-02
Particle size distribution [µm]
d10	58.8	60.3	60.2	61.4
d50	77.0	78.8	79.4	80.6
d90	105.5	108.9	112.9	116.1
Specific charge of standard toner [µC/g]	−35.8	−22.2	23.9	38.4

Powder Samples

Amines, namely tertiary amines, purine bases, and amino acids, and their hydrochloride salts were used as model drugs. The chemical structures and suppliers are shown in Table 3. Free base crystals of chlorpromazine, fexofenadine hydrate, promethazine, and flavoxate were precipitated from the aqueous solutions of their hydrochloride salts by raising pH of the solution with an aqueous solution of sodium hydroxide. All powder samples were ground in an agate mortar with 120 rounds of the pestle and sieved through a 150 µm mesh sieve for triboelectrification measurements. The charging characteristics of the powder depends on the specific surface area, and the presence of the fine powders and the particle shapes affect the charging characteristics through changes in the specific surface area. So, in this study, we found that the samples after sieving had the same specific surface area. The specific surface area of the powder samples was measured using a specific surface area measuring device (Macsorb1208, Mountech Co., Ltd., Tokyo, Japan). One gram of powder sample was loaded into the measurement cell and degassed at 40 °C for 30 min, after which the specific surface area was measured by the BET multi-point method using nitrogen gas as a probe. Table 4 shows the specific surface area of the powder sample after sieving. The specific surface area of each powder sample was 0.85 to 1.33 m²/g, and could be controlled to similar values.

Table 3. Chemical Structure and Suppliers of Samples Used in This Study

*Wako: FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan), MP: MP Biomedicals, LLC (CA, U.S.A.), TCI: Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan), Shino: Shiono Chemical Co., Ltd. (Tokyo, Japan), Prepared: Prepared from hydrochloride.

Table 4. Specific Surface Area of the Powder Sample after Sieving

Type of amine	Sample name	Specific surface area [m2/g] Average ± S.D. (n = 3)
		Free base	Hydrochloride
Tertiary amines	Procaine	1.23 ± 0.04	1.31 ± 0.02
	Chlorpromazine	0.98 ± 0.01	1.12 ± 0.01
	Fexofenadine	1.12 ± 0.02	0.89 ± 0.02
	Lidocaine	1.11 ± 0.03	1.15 ± 0.02
	Promethazine	1.33 ± 0.02	1.01 ± 0.01
	Flavoxate hydrate	0.95 ± 0.02	0.99 ± 0.01
Purine bases	Adenine	1.22 ± 0.03	1.09 ± 0.02
	Guanine	1.01 ± 0.01	0.89 ± 0.01
Amino acids	Glycine	0.85 ± 0.02	0.92 ± 0.01
	L-Arginine	1.32 ± 0.02	1.22 ± 0.01
	L-Cystine	1.10 ± 0.02	1.21 ± 0.01
	L-Histidine	1.03 ± 0.01	1.09 ± 0.01
	L-Glutamic acid	1.21 ± 0.02	1.04 ± 0.01
	L-Cysteine	1.21 ± 0.01	1.31 ± 0.02

Measurement of the Specific Charge with Standard Carrier Beads

To charge the powder sample, standard carrier beads (2970 mg) and the powder sample (30 mg) were placed in a 25 mL glass bottle and agitated for 90 s using a vortex mixer set to 5000 rpm. The charge induced by triboelectrification was quantified using a suction-type Faraday cage meter (EA-02, U-Techno Solutions Corporation, Osaka, Japan). The pre-weighed filter capsule was inserted into a suction nozzle of EA-02 (Fig. 7). The charged powder sample together with the standard carrier beads were transferred to a separating device (Fig. 7). Place the mixed standard carrier beads and sample powder into the recess of the separation device and cover with a 25 µm mesh. By suctioning with a suction nozzle from above the mesh, standard carrier beads with particle diameters larger than 25 µm are caught on the mesh, and only the powder sample is suctioned. The suction air flow rate was set to 13.2 L/min. The charges of the sample powders sucked into the suction nozzle were measured using the Faraday cage meter. The specific charges (µC/g) of the powder samples were calculated by dividing the charges of the sucked powder samples by their mass. The amount of powder sample aspirated is calculated from the difference between the mass of the empty filter capsule before the start of the measurement and the mass of the filter capsule after aspirating the powder sample. Since the filter capsule integrates the membrane filter and case, it is possible to measure the mass of the entire filter. Additionally, there is no loss of powder sample when removing the filter capsule. The error in the suction amount in this measurement is about 5 to 10% for all samples measured in this study. Measurements of each powder sample were carried out in triplicate. The measurement environment for the specific charge of each sample with standard carrier beads was a temperature of 17.6–23.0 °C and a humidity of 23–60% relative humidity.

Fig. 7. Schematic Diagram of the Suction-Type Faraday Cage Meter EA-02

Zero-Charge Margin Calculation

A representative plot required for calculating the zero-charge margin is shown in Fig. 8. The specific charges of the powder samples charged by the standard carrier beads are plotted against the specific charge of the standard toner charged by the same standard carrier bead (Table 2). The value of the specific charge of the sample increases in proportion to the magnitude of the charge donating/accepting ability of the standard carrier beads. Therefore, in the zero-charge margin calculation plot, the specific charges of the powder samples charged with each standard carrier bead line up in a straight line. The zero-charge margin is the value at the intersection point of the regression line and the abscissa axis. The zero-charge margin represents the charge-donating/accepting capacity of the carrier beads required to change the charge of the powder sample to zero. For example, if the powder sample has the zero-charge margin with a large negative value, carrier beads with higher charge donating ability, namely carrier beads that provide more negative charge, are required to reduce the amount of charge on the powder sample to zero. In other words, powder samples have more positively biased charging characteristics. Conversely, if the powder sample has the zero-charge margin with a large positive value, carrier beads with a higher charge-accepting capacity, namely carrier beads that provide more positive charge, are required to reduce the amount of charge of the powder sample to zero. In other words, the powder sample has more negatively biased charging characteristics. Therefore, when the zero-charge margin of the powder sample is negatively large, the powder sample tends to be positively charged, and conversely, when the zero-charge margin is positively large, the powder sample tends to be negatively charged. Furthermore, a large absolute value of the zero-charge margin indicates high chargeability of the powder sample. Generally, strict humidity control is required for triboelectric properties evaluation. Due to the influence of moisture in the air, the charge generated by frictional charging is repelled and the amount of charge decreases. In other words, the absolute value of the amount of charge decreases whether it is negatively charged or positively charged. On the other hand, the zero-charge margin is a value that corresponds to the charge donating/accepting ability inherent to the powder sample, so it is not affected even if the amount of charge during measurement is reduced due to humidity. Indeed, preliminary studies using riboflavin found that humidity at the time of measurement did not affect the zero-charge margin (Supplementary Fig. 2). The mean and standard deviation of the zero-charge margin were calculated from triplicate specific charge measurements using each standard carrier bead.

Fig. 8. Calculation of the Zero-Charge Margin

Surface Free Energy Measurements

The surface free energy of each powder sample was measured using a Force Tensiometer (K100, A.KRÜSS Optronic GmbH, Hamburg, Germany). Approximately 300 mg of powder sample was placed in the Washburn sorption cell and packed by placing a 500 g weight on the loaded powder sample. The test solvent was brought into contact with the bottom of the Washburn sorption cell, and the wetting speed for each solvent was measured. The dispersive component γ_d and polar component γ_p of the surface free energy were calculated from the wetting speed for each solvent. The surface polarity ratio was calculated by dividing the polar component of the surface free energy by the sum of the dispersive component and polar component. The measurement solvents used were toluene (Guaranteed Reagent, FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan), formamide (Guaranteed Reagent, FUJIFILM Wako Pure Chemical Corporation), ethylene glycol (Guaranteed Reagent, FUJIFILM Wako Pure Chemical Corporation), and butyronitrile (Tokyo Chemical Industry Co., Ltd., Tokyo, Japan).

Conflict of Interest

The authors declare no conflict of interest.

Supplementary Materials

This article contains supplementary materials.

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