**5. Not all female directors are the same**

A large and growing body of literature has investigated on the relationship between female director and CSR. However, the results are mixed (for review paper see [5]). Some studies argue that higher representation of female directors is associated with stronger CSR (for e.g. see [6, 7]), while others do not support such a relationship [10]. A possible reason for the mixed findings is that female directors may differ in personal experiences and backgrounds (e.g. political connection), and consequently exert differential impacts on CSR. Aside from that, companies' attitudes toward social and environmental concerns are multidimensional and impacted by a variety of other company and country-specific factors. Thus, in the following section, we shall analyze the link between a female director and CSR in several contexts.

#### **5.1 Masculine V.S. feminist countries**

In Saudi Arabia and Vatican City, women cannot vote, while in Yemen a woman is considered only half a witness and cannot leave her house without her husband's permission. Women encounter different types of prejudice depending on where they live. According to the World Economic Forum in 2018, there are no laws against sexual harassment in school in 123 nations, and there are no laws prohibiting it in the workplace in 59 countries. Husbands have the legal power to forbid their wives from working in 18 nations, while women are barred from starting a firm in four nations. Thus, certain cultures have stronger gender roles than others, which affects general and organizational behavior in that community [57]. Furthermore, countries that prioritize feminine traits prioritize gender equality, encourage sympathy for the weak, and elect women to multiple leadership positions. Culture can create stereotypes of roles associated with gender that can affect female's access to board [58]. To that end, if a woman currently leads a country that embodies feminine cultural norms, then by definition there is society wide support for policies that would benefit the public good. In turn, the woman leader should have more flexibility in the policies she can enact. So, one may believe that regional effect could be a possible explanation

#### *CSR and Female Directors: A Review and Future Research Agenda DOI: http://dx.doi.org/10.5772/intechopen.105112*

for the heterogeneity relationship between female participation on boards and CSR. Consistence with this notion, Seckin-Halac et al. [59] suggested that the impact of the board gender diversity on CSR is more prevalent in high gender-egalitarian societies where women are more involved in decision making. Likewise, in a study of 463 firms from 23 countries, Ringov and Zollo [60] suggested that companies based in more masculine countries, exhibit lower levels of social and environmental performance. Similarly, the recent research by Tapver [61] argues that a country's masculinityfemininity is a variable that determines the association between CSD and female representation, which has previously been overlooked in CSR reporting literature. Shoham et al. [57], on the other hand, empirically examined data from 71 nations and observed that the presence of even one female director on the board positively encourage firms to become much more proactive in environmental sustainability, regardless of the local culture. This result highlights how individual women in powerful positions can make an organization-wide difference.

### **5.2 Female V.S. male-dominated industries**

When women started to work in factories during WWII, they dispelled the idea that they could not perform the same labor as men. Despite a trend toward more equality, several nations continue to exclude women from specific industries. Manufacturing, agriculture, transportation, mining, construction, energy, and water are all examples of this. Some restrictions on when women are permitted to work are based on general safety concerns, while others are based on outdated legislation. Nevertheless, women are less likely to take positions of leadership in industries where their ability to act autonomously is limited. In another word, industry could be another important determinant in explaining the heterogeneity relationship between female boards and CSR. Indeed, there have been studies that showed support for the effects of contextual factors, such as industries, and relationship between gender diversity and CSR. For instance, Ciocirlan and Pettersson [62] show that companies employing more women and having a stronger European presence are more concerned about the climate change. This result suggested a possible moderating effect of contextual factor, such as certain industry characters under which firms are operating, on the relationship between gender diversity and climate change. In the same vein, Li et al. [47], using a sample of nonfinancial firms listed in the United States, found that the pollution creation likelihood (PCL) can have a significant effect on the relationship between gender diversity and firms' environmental policy. Specially, the positive impact of gender diversity on environmental concerns seems to be stronger when environmental pollution is greater. Even so, Kyaw et al. [37] discovered that while the effect of gender diversity boards on CSR scores is not heterogeneous across industries, it is highly heterogeneous across countries.

#### **5.3 Family V.S. non-family business**

Family businesses are those where the founders or family descendants are not only majority shareholders but also manage or sit on the board [63]. This gives them a great power over the company's management and its decisions, and close involvement in day-to-day activities, together with unlimited access to information, which allows them much closer control over management processes and employees than in the case of non-family businesses [63]. Thus, the family's intention regarding certain corporate, social, or family issues will shape business behavior and, as a result, affect business outcome. Some scholars have argued that family businesses are more likely to engage in social activities proactively because doing so preserves and enhances their nonfinancial preferences and socioemotional wealth (SEW) [64]. In another word, family managers and board members are usually more averse to the loss of SEW than to financial loss, an outlook that can significantly affect the strategic decisions taken by the firm (for meta-analysis see [65]). Consequently, directors from family businesses may be more committed to CSR and/or long-term sustainable projects, as these mechanisms are believed to facilitate the company's subsequent transfer to future generations. Furthermore, these policy decisions improve the company's image and reputation, which is an important aspect given the company is viewed as an extension and a mirror image of the family, and therefore as reflecting the fundamental values of the family members [66].

For female directors to have a real impact on a company's decision making, they need to be perceived as equal, legitimate board members [67]. For example, in a family firm, women are believed to have immaterial qualities that facilitate family relationships and thus a more informal management style. So, in family business setting, it is reasonable to assume that these qualities will enhance role played by female directors. This notion is support by García-Sánchez et al. [68], who showed that the presence of women on the boards of family businesses encourages the adoption of CSR practices in the Latin American environment. Similarly, Cruz et al. [69] argued that positive relation between firm's corporate social performance and the presence of women on family firm boards is primarily due to the presence of outsider nonfamily and insider family women directors.

While, some may argue that CSD and the strength of internal corporate governance, particularly the gender diversity board, are substitutes. Family businesses are less prone to information asymmetry [63], which leads to less opportunistic behavior [70]. As a result, control mechanisms such as voluntary information disclosure, such as CSR information, may not be necessary. Furthermore, female directors in family businesses are more likely to be affiliated to the management through family ties rather than their professional experience and knowledge, and therefore their independence is constrained [71]. Additionally, it has been reported that female directors who work in family businesses receive less consideration than their male relatives and that their work is usually underestimated [72]. Consistent with this logic, Rodríguez-Ariza et al. [73] argue that the role of female directors in promoting CSR practices could vary according to the nature of company ownership. Specifically, they suggest that female directors tend to act in accordance with family interests, putting aside their own skills, opinions, and ideas and strengthening or weakening their social responsibility orientation in accordance with the wishes of the family.

Similarly, prior research suggests that the impact of female directors on CSR may differ depending on ownership structure. Because concentrated ownership is an effective monitoring mechanism in and of itself, the need for transparency through high-quality auditing and assurance engagement is less of an issue in such firms. Buertey's [74] empirical evidence backs up this claim. They discovered that concentrated ownership has a significant moderating effect on the relationship between board gender diversity and CSR assurance. Likewise, firms with a high level of state ownership constitutes a strong pressure on corporate executives to implement CSR, which weakens the power of female directors' personal ideologies and preferences over CSR [75].


*Occupational Stress among Health Care Workers DOI: http://dx.doi.org/10.5772/intechopen.107397*

work but also equally important is the type of work culture. A conducive environment and positive work culture can be an important stress buster. Work culture is not God-gifted, it is created by effective leadership and team efforts by each one in a positive direction. Good work culture is not just a stress buster but also magnify productivity and decrease complication in patient care. A work culture of trust, transparency, respect, and openness is always helpful to reduce stress among healthcare workers.


*{4-[{(2E)-2-[(2S,3aS,3bS,6S,7R,9aS,10R,11aR)-2-(Acetyloxy)-7,10-dihydroxy-3a,3b,6,9atetramethylhexadecahydro-1H-cyclopenta[a]phenanthren-1-ylidene]-6-methylhept-5-enoyl} (carboxymethyl)amino]-2,2,6,6-tetramethylpiperidin-1-yl}oxidanyl* (**17**)

Obtained using the general method **C2**, the reaction crude reaction product was purified by silica gel column chromatography (DCM/MeOH 8:2) to yield compound **17** (12 mg, 0.016 mmol, 66%) as orange oil. *RF* 0.15 (DCM/MeOH 8:2). NMR of the corresponding hydroxylamine after the addition of hydrazobenzene. 1H-NMR (400 MHz, DMSO-*d6*) δ 8.89 (s, 1H), 5.44 (d, *J* = 8.5 Hz, 1H), 5.10 (t, *J* = 7.0 Hz, 1H), 4.18–4.13 (m, 1H), 3.98 (d, *J* = 3.7 Hz, 1H), 3.95 (d, 1H), 3.87 (d, *J* = 17.0 Hz, 2H), 3.53–3.49 (m, 1H), 2.97–2.87 (m, 1H), 2.73–2.66 (m, 1H, TEMPO), 2.26–2.17 (m, 3H), 2.10–1.97 (m, 5H), 1.94–1.82 (m, 5H), 1.81–1.70 (m, 2H, TEMPO), 1.64 (s, 3H), 1.57 (s, 3H), 1.53–1.29 (m, 6H), 1.27 (s, 3H), 1.26–1.12 (m, 3H), 1.10–0.95 (m, 14H, TEMPO), 0.88 (s, 3H), 0.84 (s, 3H), 0.79 (d, *J* = 6.7 Hz, 3H). 13C-NMR (101 MHz, DMSO-*d6*) δ 175.94, 171.54, 170.02, 154.96, 147.92, 133.53, 123.91,

74.27, 69.74, 66.27, 58.63, 58.47, 54.20, 49.43, 49.10, 48.97, 43.02, 39.25, 38.90, 36.94, 36.69, 36.09, 35.71, 31.77, 29.78, 27.52, 26.07, 23.86, 23.22, 21.37, 20.72, 20.18, 18.21, 18.15, 16.78, 14.43. HRMS (ESI) *m/z*: 726.4807 [M − H]−, calcd. for [C42H66N2O8] − 726.4819.

*{4-[{(2E)-2-[(2S,3aS,3bS,6S,7R,9aS,10R,11aR)-2-(Acetyloxy)-7,10-dihydroxy-3a,3b,6,9atetramethylhexadecahydro-1H-cyclopenta[a]phenanthren-1-ylidene]-6-methylhept-5-enoyl}(2-{[2- ({2-[6-(dimethylamino)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl]ethyl}amino)- 2-oxoethyl][3-(triphenylphosphaniumyl)propyl]amino}-2-oxoethyl)amino]-2,2,6,6 tetramethylpiperidin-1-yl}oxidanyl bromide* (**18**)

Obtained using the general method **A** in 0.013 mmol scale (3-aminopropyl) triphenylphosphonium bromide and paraformaldehyde were used, then fusidic acid derivative **17** and Yudin's isonitrile were added. The crude reaction product was purified by silica gel column chromatography (DCM/MeOH 8:2) to yield compound **18** (6 mg, 0.004 mmol, 34%) as yellow powder. *RF* 0.12 (DCM/MeOH 8:2). NMR of the corresponding hydroxylamine after the additon of hydrazobenzene. 1H-NMR (400 MHz, DMSO-*d6*) δ 8.57 (d, *J* = 8.8 Hz, 1H), 8.54 (d, *J* = 7.5 Hz, 1H), 8.51 (d, *J* = 8.3 Hz, 1H), 7.87–7.72 (m, 15H), 7.18–7.15 (m, 1H), 5.44 (q, *J* = 15.3, 12.0 Hz, 1H), 5.10 (d, *J* = 10.6 Hz, 1H), 4.62 (t, *J* = 7.3 Hz, 2H), 4.20–4.14 (m, 1H), 4.08–3.97 (m, 6H), 3.62–3.52 (m, 4H), 3.37 (d, *J* = 7.9 Hz, 2H), 3.16 (s, 4H), 3.10 (s, 6H), 2.95–2.88 (m, 1H), 2.69–2.62 (m, 1H), 2.46–2.11 (m, 8H), 2.11–1.92 (m, 7H), 1.50 (s, 3H), 1.47–1.32 (m, 6H), 1.30 (s, 3H), 1.24 (s, 3H), 1.15–0.95 (m, 17H), 0.89 (s, 3H), 0.85 (s, 3H), 0.80 (d, *J* = 6.7 Hz, 3H). 13C-NMR (101 MHz, DMSO-*d6*) δ 171.12, 169.83, 169.46, 168.61, 163.83, 163.15, 156.51, 148.71, 135.13, 135.10, 133.60, 133.49, 132.17, 131.82, 131.51, 130.42, 130.29, 129.73, 128.76, 128.46, 124.98, 123.47, 122.99, 118.40, 117.82, 113.56, 112.99, 73.58, 69.19, 65.74, 58.08, 57.89, 54.62, 51.14, 48.94, 48.58, 48.16, 44.36, 43.54, 42.08, 38.59, 36.66, 36.42, 36.33, 36.26, 36.16, 35.84, 31.78, 30.21, 27.01, 25.55, 23.46, 23.33, 21.07, 20.80, 20.67, 20.08, 19.64, 18.37, 17.84, 17.71, 17.49, 16.25. HRMS (ESI) *m/z*: 1352.7621 [M]+ , calcd. for [C81H105N6O10P]+ 1352.7624.

#### *4.2. EPR Spectroscopy and Sample Preparation*

X-Band (~9.43 GHz) room temperature CW-EPR measurements were performed on a Magnettech MiniScope MS400 benchtop spectrometer (Magnettech, Berlin, Germany). Spectra were recorded with a microwave power of 3.16 mW, 100 kHz modulation frequency, modulation amplitude of 0.1mT and 4096 points. The final spectra were accumulations of 10 scans, each took 60 s. The samples were dissolved in methanol. Therefore, to reduce the line broadening effect due to the dissolved oxygen in the solvent, all samples were flushed with argon before EPR measurements.

#### *4.3. Biology*

#### 4.3.1. Cell Lines and Cultivation

PC3 and HT29 cell lines were supplied by the Leibniz Institute of Plant Biochemistry. The cells were grown in RPMI 1640 completed medium (supplemented with 10% FCS, 1% glutamine, and 1% penicillin/streptomycin) at 37 ◦C and 5% CO2. Cells were seeded at 5 × 103 cells/well in 96-well plates for viability determination and 1.5 × 105 cells/well in 6-well plates for flow cytometry and western blotting.

#### 4.3.2. MTT and CV Assays

For the fast screening the two cell lines were treated with 0.1 and 10 µM of the synthesized compounds 6-12, and 18 for 48 h. The compounds which showed anticancer activity was further analyzed to determine their IC50, in which, each compound was tested in 7 different concentrations (100, 50, 25, 12.5, 6.25, 3.125, 1.56 µM) for 48 h. Afterward, for the CV assay, the cells were fixed by 4% paraformaldehyde for 15 min at RT and then the cells were stained with 0.1% CV solution for 15 min. Subsequently, the cells were washed with dd H2O, dried overnight and the dye was dissolved using 33% acetic acid. For MTT assay, the cells were incubated with MTT (0.5 mg/mL) for 20 min. Then, the

MTT solution was removed and the dye was dissolved using DMSO. The dissolved dyes were measured using an automated microplate reader (Spectramax, Molecular Devices, San José, CA, USA) at 570 nm with a background wavelength of 670 nm. The IC50 values were calculated using the four-parameter logistic function and presented as the mean and all assays were performed in three biological replicates. The cell viability was expressed as a percentage compared to a negative control which was cells treated with complete medium and a positive control which was cells treated with digitonin (125 µM) [41,42].

#### 4.3.3. Apoptosis Analysis

The PC3 cells were prepared in a 6 well plate, treated with IC50 and 2 × IC50 of compound **8** (7.4 and 14.9 µM), and incubated for 48 h at 37 ◦C and 5% CO2. After the incubation, cells were stained by AnnV and PI (5 µL of AnnV, 2 µL of PI in 100 µL PBS) to determine apoptosis using flow cytometry (FACSAria III, BD Biosciences, Franklin Lakes, NJ, USA). The procedure was carried out according to the manufacturer's supplied instructions [42].

#### 4.3.4. Cell Cycle Analysis

The PC3 cells were prepared in a 6 well-plate and treated with IC50 and 2 × IC50 of compound **8** (7.4 and 14.9 µM) and incubated for 48 h at 37 ◦C and 5% CO2. Afterward, the cells were fixed in 70% ethanol overnight at 2 ◦C and then, stained with 1 µg/mL of DAPI at room temperature for 10 min. At last, the cells were analyzed by flow cytometry (FACSAria III) [42].

#### 4.3.5. Western Blot Analysis

PC3 cells were cultivated with an IC50 dose of **8** for 2 h, 6 h, 12 h, 24 h, and 48 h. The cell lysis was performed using protein lysis buffer (62.5 mMTris–HCl (pH 6.8), 2% (*w*/*v*) SDS, 10% glycerol, and 50 mM dithiothreitol). The proteins were electrically separated using 12% SDS-polyacrylamide gels where a PageRuler prestained ladder was used as a protein molecular weight marker. The proteins were electrically transferred to nitrocellulose membranes by western blot system (Owl HEP-1, ThermoFisher Scientific, Schwerte, Germany). The membranes were blocked by 5% (*w*/*v*) BSA in PBS with 0.1% Tween 20 for 1 h at RT. Afterwards, blots were incubated overnight at 4 ◦C with α/β-Tubulin rabbit Ab, Caspase-3 rabbit Ab, β-actin rabbit Ab, and Bcl-XL rabbit Ab. As a secondary antibody Anti-rabbit IgG, HRP-linked Antibody was used. Bands were visualized using an ECL Prime Western Blotting System.

#### 4.3.6. Investigation of ROS Production

For the detection of reactive oxygen and nitrogen species, PC3 cells were stained with 1 µM of DHR solution in 0.1% PBS for 10 min. Afterwards, the cells were treated with IC50 and 2 × IC50 of compound **8** for 48 h. After 48 h, cells were trypsinized, washed with PBS, and then analyzed with flow cytometry [43,44].

#### *4.4. Microscopy*

#### Fluorescent Microscopy

PC3 cells were seeded in a 6-well plate for 24 h at 37 ◦C and 5% CO2. Afterward, cells were stained with 0.1 µM of MitoTrackerTM Deep Red in a complete medium for 15 min (based on the manufacturer's protocol). The cells were washed twice with PBS. After washing, cells were treated with the IC50 of the tested compound for 24 h. The cells were washed twice with PBS, upon which 1 mL of medium was added. Finally, the cells were observed using GFP and Texas Red channels using LSM700 (Carl Zeiss, Jena, Germany) and EVOS FL AUTO (ThermoFisher, Schwerte, Germany).

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/10 .3390/ijms22137125/s1. Table S1. EPR charactersitics for nitroxides 6-12, 14, 16-18; 1H-, 13C-NMR spectra and HPLC-profiles of products 6-12, 14, 16-18.

**Author Contributions:** H.N.S. synthesized and analyzed the compounds, wrote the initial manuscript, I.M. carried out the biological experiments and assisted in the biological data compilation, H.H. co-analyzed the spectroscopic data and assisted in the initial manuscript, A.H.R. and H.H.H. measured and analyzed the EPR-spectra, G.N.K. oversaw the biological assay data and assisted in the final manuscript, D.H. oversaw the EPR-analysis and co-designed the project, B.W. designed and coordinated the project, finalized the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** Hidayat Hussain gratefully acknowledges support by the AvH-foundation.

**Conflicts of Interest:** The authors declare no competing financial interest.

#### **References**

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**4. Part III: strategizing technology is a process, not an event**

It is quite a challenging tasks to develop technology strategy of a large multinational corporation. In recent years the changes on all fronts, the economic, political, social and environment, are extremely rapid. These changes impact businesses and their long-term and short-term strategies. Just most recent global catastrophic event, the pandemic, has affected and impacted entire population of the globe and consequently businesses around the globe. The painful 'Brexit' has created newer issues in Europe and countries dealing with UK. Add to this the Ukraine invasion of Russia. The resulting inflation and shortages of various necessities including energy has posed completely new perspective of the world to business leaders.

**Figure 5.** *Two important input blocks to strategy formulation process.*

The Technology Strategist cannot isolate herself from this new rapidly changing world full of unanticipated events. The strategy formulated by her has to be:

It is critical to attend to the process of strategy formulation, rather than just the strategy itself. I propose to focus on the strategy formulation process instead of final product as technology strategy. Letza et al. [19] emphasize that no business process can be isolated from power, social relations and organizational context. I present here the Technology strategy formulation process in two blocks. First block to complete initial assessment of Technology and Economic aspects, followed by the second block adapted from Vaidya [20].

The two blocks shown in **Figure 5** indicate important inputs that are required for Technology Formulation Process of a multinational company. The left block of Technical, Operational and Economic considerations was discussed in part I, here we will explore the second block of Socio-Political dimensions. In order to get clarity, I have exploded the second block in **Figure 6**.

IPCRC model in **Figure 6** is an interesting model that takes into account social and political interests of a multinational company. It caters to the socio-political environment of a multinational company, proposing the activities that need to be completed while developing technology strategy. Here is a short description of each activity.

I—Identify the interest groups and their power bases: the interest groups carry their own norms and ways of work. It is important for strategist to understand the power bases behind such groups. As an example the largest business division in a multinational company may have higher power to influence decisions.

P—Acknowledge and recognize political aspects: the affiliate company heads and senior managers may have own ambitions. It is useful to know these persons and their thoughts.

#### **Figure 6.**

*IPCRC model adapted from Vaidya [20].*

C—Central coordination and mutual adjustment: it is useful to know the coalitions and their requirements beforehand. The give and take with necessary adjustments rather than mandate produces better result.

R—Remedial and serial strategy deployment: a step by step implementation proves better than the big bang approach. It allows any remedial measure to be incorporated as one progresses.

C—Collibratory intervention: it is always a possible that the higher level intervention has to be accommodated, such as a directive to place a data center in a particular region or having a preferred network provider in a country. The strategist needs to make room for such a possibility.

By following this IPCRC model a strategist will be able to develop an agreeable strategy which becomes easier to execute in various cultures and geography. Considering deployment challenges at an early stage of strategy formulation results in a executable strategy.

Since 2020 the world has faced pandemic, shortages of supplies, human tragedy, the oil shock, the war between Russia and Ukraine, the emerging tensions in Asia, many such worrisome issues. As a result, the world order, the relations amongst various sovereign states are being redrawn all the time. The globalization seems to be giving way to nationalization, there are people who believe that deglobalization is already in offing. In the dynamic and ever changing geopolitical and national and social interests it is extremely critical that the strategist focuses on strategy formulation process. The product, the strategy, is important however one has to build ability to quickly reform it using right kind of processes.


**5. Conclusions**

Vegetable products are pivotal in human health and their daily consumption is highly recommended due to their high content in phytochemicals with diverse beneficial health effects. The vegetable crops presented in this review, namely leafy and fruit vegetables and species where other plant parts are consumed, are well known and widely consumed throughout the world, although their colored variants are not always accepted by consumers and proper marketing is needed to introduce them to the public. Currently, the food and beverage industry is seeking for natural alternatives of synthetic compounds to satiate market demands for "non-chemical additives" food products. Therefore, the broad color palette the presented vegetables exhibit not only could diversify human diet and make food products more attractive to consumers and increase their appeal, but also could be proved as valuable sources of natural coloring agents. Under the circumstances, future research should focus on the identification of those promising coloring agents and the establishment of efficient and sustainable techniques for their isolation. Other future requirements, include breeding and agronomic protocols that could improve pigments content in the final produce, as well as post-harvest and processing conditions to increase extraction efficiency of natural coloring agents. Finally, the mechanisms of actions related with the health effects and antioxidant activities of coloring compounds have to be revealed and valorized in the pharmaceutical and food industry for the design of novel functional foods and drugs.

**Funding:** This work was supported by the USDA National Institute of Food and Agriculture and Hatch Appropriations under Project #PEN04723 and Accession #1020664; The authors are grateful to Foundation for Science and Technology (FCT, Portugal) and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2019); to FEDER-Interreg España-Portugal programme for financial support through the project 0377\_Iberphenol\_6\_E and TRANSCoLAB 0612\_TRANS\_CO\_LAB\_2\_P; the European Regional Development Fund (ERDF) through the Regional Operational Program North 2020, within the scope of project Mobilizador Norte-01-0247-FEDER-024479: ValorNatural®.

**Conflicts of Interest:** The authors declare no conflict of interest.


*2.2. Methods*

#### 2.2.1. Solid Dispersion Preparation Using Supercritical Carbon Dioxide (scCO2)

Bicalutamide and carriers, i.e., Macrogol 6000 or Poloxamer® 407, were mixed in a 1:1 weight ratio and loaded into a high-pressure reactor BR-300 (Berghof Products + Instruments GmbH, Eningen unter Achalm, Germany) equipped with a magnetic stirrer MR Hei-Standard (Heidolph Instruments, Schwabach, Germany), a heating mantle and a CHY 700T thermometer (CHY Firemate Co., Tainan City, Taiwan). To obtain supercritical conditions, carbon dioxide was pumped and compressed into a high-pressure reactor by a syringe pump SFT-10 (Supercritical Fluid Technologies Inc., Newark, NJ, USA). The process was conducted at 50 ◦C and 150 bar with Macrogol 6000 as a carrier, and at 60 ◦C and 160 bar with Poloxamer®407. In both cases, the magnetic stirrer was set at 500 rpm. The process parameters were monitored during the whole operation. The total mass of powder introduced into the high-pressure reactor was equal to 2 g. After the process, solid dispersions were pulverized through 1.8 mm sieve.

#### 2.2.2. Scanning Electron Microscopy (SEM)

The morphological characterization of the samples was conducted using a Phenom Pro desktop electron microscope (Phenom World, Thermo Fisher Scientific, Waltham, MA, USA). Powdered samples were placed on the conductive adhesive tape glued to the specimen mount and measured in a holder for non-conductive samples. The acceleration voltage was equal to 10 kV. The stream of argon was used to remove the powder loosely bounded to the tape before the measurement.

#### 2.2.3. Laser Diffraction Measurements

A Malvern Mastersizer 3000 (Malvern, UK) equipped with a HydroEV unit was used to determine particle size distribution. The samples were analyzed by the wet method using cyclohexane (reflective index, RI = 1.426) as a dispersant. Fraunhofer diffraction theory was applied to find the relationship between the particle size and the light intensity distribution pattern. The reported data represents the medians (D50 values) calculated as averages from ten series of measurements of each sample and the distribution span.

#### 2.2.4. Powder X-Ray Di ffraction (PXRD)

The diffraction patterns of the samples, i.e., pure substances, solid dispersions, and tablets, were registered at ambient temperature using an X-ray Rigaku Mini Flex II diffractometer (Tokyo, Japan) with a 5◦/min step. Samples were scanned from 3◦ to 45◦. Monochromatic Cu K α radiation (λ = 1.5418 Å) was used.

#### 2.2.5. Di fferential Scanning Calorimetry (DSC)

The thermal properties of the solid dispersions, raw bicalutamide, and carriers were examined using a di fferential scanning calorimetry (DSC) 1 STARe System (Mettler-Toledo, Greifensee, Switzerland). The measuring device was equipped with an HSS8 ceramic sensor with 120 thermocouples and a liquid nitrogen cooling station. The instrument was calibrated for temperature and enthalpy using zinc and indium standards. The glass transition temperature, crystallization, and melting were determined as the midpoint of the glass transition step, the onset of the exothermic peak, and the peak of the endothermic event, respectively. The samples were measured in an aluminum crucible (40 μL). The sample mass used for DSC experiments varied between 7 to 10 mg. All measurements were carried out with and without annealing (T = 323 K; t = 10 min). The experiments were performed from 273 to 478 K, with a heating rate equal to 10 K/min.

#### 2.2.6. Preparation of Tablet Blends

The composition of each three formulations containing raw BCL or solid dispersions are presented in Section 3.3. Bicalutamide or solid dispersions were manually mixed with excipients: cellulose microcrystalline as a filler for 3 min, sodium starch glycolate as a disintegrant for 3 min and magnesium stearate as a lubricant for 1 min, in the porcelain dish.

#### 2.2.7. Tableting Process and Tablet Characterization

The compression of tablets blends was performed using a single punch tableting machine (Korsch EK0, Berlin, Germany) equipped with the round flat punches which are 8 mm in diameter; each tablet type contained 50 mg of the active substance. Punches were equipped with tensiometers connected to a computer by Esam Traveler 1 Data Acquisition System Master Unit, type 0508-S-ESA (ESA Messtechnik GmbH, München, Germany). To obtain tablets that possess satisfactory properties, the pressure force applied on a blend containing raw bicalutamide and solid dispersions was equal to 7 kN (140 MPa) and 2 kN (40 MPa), respectively.

The mass uniformity of tablets was measured based on the method described in European Pharmacopoeia (Ph. Eur.) 9.0. The hardness, thickness and diameter of 20 randomly selected tablets were measured using hardness tester apparatus (VanKel VK200, Agilent Technologies, Santa Clara, CA, USA) and expressed as a mean value with standard deviation. The friability test was performed using a Pharma Test apparatus (Pharma Test Apparatebau AG, Hainburg, Germany). The disintegration time of the tablets was measured in distilled water at 37 ◦C using an Electrolab ED-2 SAPO (Electrolab, Mumbai, India) disintegration apparatus at 30 strokes/min.

#### 2.2.8. Dissolution Studies

The dissolution studies were carried out using the method recommended by the Food and Drug Administration (FDA) for BCL tablets, i.e., United States Pharmacopeia (USP) paddle apparatus (II type), and the parameters, i.e., 50 rpm, 1000 mL of 1% SLS solution, 37 ± 0.5 ◦C. The analysis was performed in a Vision Elite 8 apparatus (Hanson Research, Chatsworth, CA, USA) equipped with a Vision G2 AutoPlus Autosampler, and an AutoFill sample collector (Hanson Research, Chatsworth, CA, USA). Samples, i.e., raw BCL, physical mixture, and solid dispersions obtained by supercritical carbon dioxide methods, containing the equivalent of 50 mg of the active substance, as well as prepared tablets, were poured into the beakers. A volume of 5 mL of the samples was withdrawn from each dissolution vessel at predefined intervals, filtered, diluted, and assayed spectrophotometrically at λ = 272 nm (UV-1800 Shimadzu, Shimadzu Corporation, Kyoto, Japan). After the collection of each sample, the dissolution medium was replaced with the same volume of pure one. The tests were carried out in triplicate, and the results represent averages with their standard deviations.

#### 2.2.9. Contact Angle Measurements

A DSA255 drop shape analyzer (Krüss, Hamburg, Germany) was used to measure the contact angles using a sessile drop technique. A droplet of distilled water of volume equal to 2 μL was deposited on the surface of prepared tablets.

## 2.2.10. Stability Studies

Tablets were packed into PVC/Al blisters and placed in climate chambers (Memmert GmbH + Co. KG, Schwabach, Germany) and stored in either 25 ◦C/60% relative humidity (long-term conditions) or 40 ◦C/75% relative humidity (accelerated conditions). After six-month storage, tablets were analyzed for the following parameters: mass, hardness, thickness, contact angle, and dissolution rate of bicalutamide. The solid dispersion was analyzed after its preparation. The tablets' properties were evaluated just after the preparation and after the stability studies.

#### **3. Results and Discussion**

#### *3.1. Solid-State Characteristics of Solid Dispersions*

Based on the SEM results (Figure 1), raw bicalutamide exhibited elongated crystals of smooth surfaces. They were hexagonal and 30–160 μm long (Figure 1A). The median of the particle size distribution determined using a laser diffraction measurements laid was 81.7 μm (Table 1). The analysis of microphotographs of carriers indicated that Macrogol 6000 exhibited irregular particles of smooth surface and length not exceeding 100 μm (Figure 1B). In the case of the particles of Poloxamer® 407, they were smooth and spherical, of a diameter varying between 50 μm and 250 μm (Figure 1C). The medians of the particle size were 113 μm and 180 μm for PEG6000 and PLX407, respectively (Table 1). However, the distribution span for PEG6000 was much higher than for the other compounds, which indicated a wide distribution. The analysis of the particle size distribution revealed the presence of dust particles in each sample visible as a distribution tail within the region below 10 μm (Figure 2). In the case of bicalutamide and PLX407 the distributions were narrow and symmetrical (despite said tails), while in the case of Macrogol, the particle size was distributed uneven, with a maximum shift towards big particles. The distribution curve is skewed to the left, which can explain the differences between the size calculated from the SEM picture and laser diffraction measurements. The particles visualized using an electron microscope represent the fraction described by the extended distribution shoulder visible on the left side of the plot (pictures showing greater particles at the same magnification were not representative enough and are not presented here), while the laser diffraction assessed all the particles present in the sample.

After the treatment of BCL-PEG6000 binary mixtures by a supercritical carbon dioxide at 130 bar and 50 ◦C in the high-pressure reactor, solid dispersions were pulverized and white, free-flowing powders were obtained. In the case of solid dispersion with Poloxamer® 407, prepared at higher process parameters, i.e., pressure 140 bar, temperature 60 ◦C. The obtained sample also was white; however, its structure was foamy. After pulverized, white, free flowing powder was obtained.

Solid dispersions morphology was analyzed using SEM. The obtained results showed that the sample containing Macrogol 6000 exhibited irregular particles of a smooth surface with well-visible incorporated particles of different contrast. They were identified as the crystals of the active substance (Figure 1D). The particles of the solid dispersion with Poloxamer® 407 were rough, with visible inclusions of BCL crystals (Figure 1E).

**Table 1.** Particles size distribution of raw bicalutamide and carriers, results obtained by the laser diffraction method.

**Figure 1.** SEM image of raw bicalutamide (**A**), PEG6000 (**B**), PLX407 (**C**), BCL-PEG6000, (**D**) and BCL-PLX407 (**E**) solid dispersions.

The laser diffraction measurements revealed that solid dispersions exhibited a wide particle size distribution, in both cases skewed to the left, with two visible modes (Figure 2). The median of BCL-PEG6000 solid dispersion particles lay above 1 mm, which could be a result of the intense laser light diffraction on big particles and the presence of a well-resolved mode of the distribution curve. In the case of solid dispersion with Poloxamer® 407, the median of the particle size distribution was equal to 356 μm (Figure 2).

The thermal properties were obtained using differential scanning calorimetry (DSC). The presence of an endothermic peak with an onset at 196 ◦C corresponds to the melting temperature of form I polymorph of bicalutamide (Figure 3). After the treatment with supercritical CO2, decreases in bicalutamide crystallinity in both obtained solid dispersions were noticed. This was confirmed by a decrease in the melting temperature of the active substance. For the solid dispersion prepared with Macrogol 6000, the melting of bicalutamide was recorded as an onset at 152.6 ◦C. The presence of the second endothermic peak with the onset at 60 ◦C corresponds to the melting point of the carrier. In the case of solid dispersions with Poloxamer® 407, the glass transition temperature was recorded at −6.2 ◦C. Bicalutamide crystallization occurred at 145.4 ◦C, while it melted at 167.4 ◦C. This indicated that the treatment with supercritical CO2 led to drug amorphization. However, the system was characterized

by very low physical stability in ambient conditions, expressed as a negative value of Tg. It resulted from low values of PLX407 Tg, −65 ◦C, combined with Tg of amorphous form of bicalutamide equal to 55 ◦C [36,37].

**Figure 2.** The particle size distribution of raw bicalutamide, polymers, and solid dispersions.

**Figure 3.** Scanning differential calorimetry of raw bicalutamide, polymers, and solid dispersions.

The molecular structure of each compound and solid dispersions was assessed using X-ray diffractometry. The diffraction pattern of raw bicalutamide is characteristic for crystalline form I polymorph, rich in distinctive Braggs peaks at 2θ equal to 6.2◦, 9.5◦, 12.3◦, 14.3◦–14.6◦, 17.0◦, 19.0◦, 20.0◦, and 24.0◦ (Figure 4). In the case of the used carriers, the diffraction patterns showed only two signals for each component, resulting from the semi-crystalline nature of the polymers. A decrease in the drug crystallinity was noticed in both types of solid dispersions. It was demonstrated by the decrease in the intensity and broadening of the peaks (Figure 4). Interestingly, the positions of the peaks shifted in comparison with the initial form of the drug. This indicated the recrystallization into the second polymorph of BCL, with the Braggs peaks positioned at 12.8◦, 17.4◦, 19.5◦, 23.7–24.3◦, and 25.4◦ [27].

**Figure 4.** X-ray diffraction of raw bicalutamide and carriers, i.e., Macrogol 6000 and Poloxamer® 407, and solid dispersions.

#### *3.2. Bicalutamide Dissolution*

The preparation of solid dispersions using the supercritical carbon dioxide method with Macrogol 6000 and Poloxamer®407 led to a decrease in bicalutamide crystallinity, which resulted in dissolution improvement. The dissolution profiles of bicalutamide were very similar in both types of solid dispersions (Figure 5). After 1 h, 74.80 ± 1.66% of the drug dissolved from BCL-PEG6000 solid dispersion, and 77.43 ± 6.01% from the BCL-PLX407 one. The amount of bicalutamide dissolved from solid dispersions was approximately nine times greater than that determined for crystalline bicalutamide (form I polymorph), as 8.85 ± 1.02% of pure drug dissolved. No significant differences in the drug dissolution characteristics were noticed after the physical mixing of the active substance with any of the two polymers (approximately 12% of drug dissolved from each mixture). This confirms that the hydrophilic character of the carriers was not a crucial factor driving drug dissolution, and the dissolution improvement was related to the changes that occurred after the treatment with supercritical CO2. During the process, the drug substance was dissolved in the polymer in supercritical CO2, and the magnetic stirrer ensured uniform mixing of the ingredients. In the process of carbon dioxide removal, the sample solidified as a result of the rapid decrease in pressure. It provided homogenous distribution of the drug substance in the carrier.

**Figure 5.** Dissolution of bicalutamide from solid dispersions with Macrogol 6000 and Poloxamer®407 in comparison with physical mixtures and crystalline bicalutamide (form I polymorph).

#### *3.3. Characteristics of Tablets Containing BCL-PEG6000, BCL-PLX407 Solid Dispersions and Raw BCL*

The three types of tablets were prepared using the direct compression method. The BCL-PEG6000 and BCL-PLX407 solid dispersions and raw bicalutamide were mixed with cellulose microcrystalline, sodium starch glycolate, and magnesium stearate to formulate tablets (Table 2). The obtained results revealed that hardness, thickness and friability were satisfactory.

**Table 2.** The composition of tablets containing BCL-PEG6000 and BCL-PLX407 solid dispersions and raw bicalutamide.

The analysis of hardness showed that the tablets containing solid dispersions were characterized by higher hardness than those with raw bicalutamide (Table 3). This resulted from the binding properties of the used carriers, which also affected the disintegration time. Tablets containing solid dispersions disintegrated for longer than tablets with raw bicalutamide. Moreover, the tablets with BCL-PLX407 solid dispersion exhibited a six-fold longer disintegration time than those with BCL-PEG6000 solid dispersion, 24 min 22 s and 4 min 23 s, respectively. The difference was caused by the properties of poloxamer, which behaves like a binding substance [38]. During the compression process, particles tend to aggregate and increase the number of direct contact points between them, which extends tablet disintegration. Despite the surface activity and solubilizing activity of the polymer, a great content of poloxamer in the sample can retard tablet disintegration due to the gelling properties of the polymer [38–40].

**Table 3.** The properties of tablets containing solid dispersions (SD) and crystalline bicalutamide.

The use of hydrophilic polymers in solid dispersion resulted in an increase in the wettability of the surface in comparison with the tablets containing raw bicalutamide. The tablets containing solid dispersions were more hydrophilic. They exhibited lower values of contact angles than the tablets with crystalline BCL:50.8◦ and 55.8◦ for the tablets containing PEG6000 and PLX407, respectively.

The X-ray diffraction analysis indicated that the active substance was amorphous. The presence of a broad halo instead of the Braggs peaks characteristic for crystalline drug substances, visible in Figure 4, indicated that bicalutamide was amorphous in all tested tablets (Figure 6). We assumed that this resulted from the propensity of bicalutamide to undergo activation upon mechanical treatment [10,12,27]. This means that the material gains some amount of energy which needs to be released. The relaxation of the stress field, applied during compression, occurs in several ways, including amorphization, as in the case of investigated tablets.

**Figure 6.** Diffraction patterns of tablets containing raw bicalutamide and solid dispersions.

As shown in Figure 7, bicalutamide release from the tablets indicated that the use of solid dispersions in tablets significantly enhanced drug release. This resulted from the improved wettability and amorphization of bicalutamide upon compression. After 1 h, 80.16 ± 8.56% and 56.61 ± 4.84% of the drug released from the tablets with PEG6000 and PLX407 solid dispersions, respectively. From tablets containing raw bicalutamide, 17.99 ± 1.70% dissolved, which was two times greater in comparison with the drug alone. Although the dissolution of bicalutamide from both solid dispersions was comparable at each time point, the differences in profiles were noticeable between solid dispersions (Figure 5) and corresponding tablets. After 30 min, 28% more bicalutamide was dissolved from tablets containing BCL-PEG6000 solid dispersion in comparison with the BCL-PLX407 tablets.

**Figure 7.** Dissolution profile of tablets containing solid dispersions and raw bicalutamide.

The prepared tablets were evaluated for stability upon storage. The results of the studies after six months revealed that the storage in both the long-term and accelerated conditions affected the properties of the tablets (Table 4) in comparison with tablets analyzed immediately after preparation (please refer to Table 3).

**Table 4.** Properties of tablets after six months of storage.

In both types of tablets, drug release decreased after storage, regardless of the storage conditions (Figure 8A,B). However, less noticeable changes occurred for tablets stored at 25 ◦C and 60% RH. The amount of dissolved bicalutamide was 70.42% and 50.82% in the case of tablets containing solid dispersion with PEG6000 and PLX407, respectively. On the contrary, 32.01% of bicalutamide was released from BCL-PEG6000 tablets stored in accelerated conditions, which was a 2.5-fold decrease, in comparison with the freshly prepared tablets.

**Figure 8.** Release profiles of bicalutamide from tablets containing solid dispersion with either PEG6000 (**A**) or PLX4087 (**B**) after stability studies, in comparison with tablets analyzed after preparation.

Moreover, after the six-month stability studies, no phase transition of the drug substance occurred (Figure 9). The di ffraction patterns did not change in comparison with those measured for tablets directly after compression (Figure 6). The bicalutamide remained amorphous, as confirmed by the halo visible in the di ffractograms (Figure 9). This indicated that water absorbed from the air in the climate chambers did not cause drug recrystallization.

**Figure 9.** Diffraction patterns of bicalutamide in tablets with solid dispersions after stability studies.


**5. The Republic of Suriname**

#### **5.1 Generalities**

The Republic of Suriname is located on the northeast coast of South America, bordering the Atlantic Ocean and surrounded by French Guiana, Brazil, and Guyana (**Figure 1**). Roughly 80% of the approximately 600,000 inhabitants live in the capital city of Paramaribo and other urbanized areas in the northern coastal zone of the country (**Figure 1**). The remaining 20% resides in the rural-coastal areas and the southern-rural interior, which comprises approximately 90% of the country's land surface and largely consists of sparsely inhabited savanna and undisturbed, dense tropical rainforest with a very high animal and plant biodiversity [25, 26] (**Figure 1**).

Suriname's most important economic means of support are crude oil drilling, gold mining, agriculture, fisheries, forestry, and ecotourism [110]. These activities

substantially contributed to the gross domestic product in 2020 of about USD 3 billion [111], positioning Suriname on the World Bank's list of upper-middle-income economies [112]. Suriname's population is among the most varied in the world, comprising Amerindians (the original inhabitants of the country) as well as descendants from enslaved Africans, indentured laborers from Asia, and European settlers, as well as immigrants from various Latin American and Caribbean countries [113]. All ethnic groups have preserved much of their original culture and identity, still practicing the religion they were raised with, speaking the language from their country of origin, maintaining their specific perceptions of health and disease, and adhering to their ethnopharmacological traditions [114, 115].

As a result, the use of various forms of traditional medicine is deeply rooted in the country, despite the broad availability of affordable modern health care [114, 115]. This inclination, together with the easy access to raw plant material from Suriname's rich biodiversity, probably accounts for the frequent use of traditional herbal medications in the country, either alone or in conjunction with prescription medicines [114, 115]. As in many other regions throughout the world, parts from Fabaceae members are often used for preparing the traditional medicines. The botanical knowledge to identify useful and edible plants has probably been obtained from ancient knowledge from the country of origin, by exchanging information with other cultures, by observing other peoples and animals, and by trial and error [114, 115].

#### **5.2 Fabaceae in Suriname**

The Fabaceae plant family is the most common family in tropical rainforests and dry forests of the Americas and Africa [116]. This plant family is also abundantly present in Suriname, and all growth forms—from dwarf shrubs and broadleaf evergreen trees to lianas and plants with bulbs or rhizomes—can be encountered between the northern coastal plain and the heavily forested and mountainous interior of the country. The exact number of genera and species in Suriname is not known, but according to the Checklist of the Venezuelan Guiana, there were 1032 species and 146 genera in the Guiana Shield in the year 2007 [28]. These figures are well in accordance with those from the National Herbarium of Suriname, which has 146 Fabaceae genera and 531 species from the Guiana Shield in its repository, 132 genera and 429 species of which have been collected in Suriname [28]. Thus, the Fabaceae species in Suriname can be estimated to constitute roughly 10% of the total number of approximately 5100 vascular plants in the country.

Like in many other parts of the world, several of the Surinamese Fabaceae species are used for a diversity of medicinal purposes. These species of Fabaceae have extensively been dealt with in several comprehensive publications on medicinal plants used in Suriname [117–125], and their total amounted to about 60 of the roughly 800 medicinal plant species. Thirty-nine of the medicinal Fabaceae species (about 65%) belong to the subfamily Faboideae, 16 (about 25%) to the Caesalpinioideae, 4 (about 7%) to the Detarioideae, and only 1 (about 2%) to the Cercidoideae. This distribution is more or less in accordance with that of the Fabaceae subfamilies throughout the world [75].

So far, scientific data to support the health claims of the Surinamese medicinal species of Fabaceae are scant. It is also not certain whether these claims may be based on the relatively high content of phytochemicals with antioxidant activity of these plants that, as mentioned above, seems to be one of the hallmarks of this plant family.


**5. Strengths and Limitations**

This study had several strengths and limitations. First, to the best of our knowledge, this is the first study in the Kingdom of Bahrain and one of few in the region to evaluate the association between sociodemographics, lifestyle, dietary habits, and some medical conditions with *H. pylori* infection. Second, a short version-13 item-FFQ previously validated by Yassibas [31] was used to assess dietary intake, FFQ is considered one of the best dietary tools to assess the relationship between diet and disease. Furthermore, the internal consistency and reliability of this tool were improved by adding items from the Bahraini FFQ that is in process of validation and other food items and beverages that were related to *H. pylori* infection in previous studies. Third, the data were collected through telephone interviews and not self-administered, so that the interviewer might clarify any misunderstandings if needed and minimize missing information. Fourth, *H. pylori* status was determined upon upper GI endoscopy biopsy testing and/or UBT, both of which have high diagnostic accuracy. Finally, medical data were retrieved from the patients' medical records, minimizing any self-reporting or categorization bias. Some limitations regarding this study should be considered when interpreting the results. The data collection was conducted during the COVID-19 pandemic; within this period some lifestyle and dietary habits might be affected. In addition, due to the regulations related to that period, some non-urgent investigations/procedures were rescheduled, which affected our reach to the targeted population. Due to that reason, we included any patient who had done the *H. pylori* testing within the previous 18 months by either UBT or upper GI endoscopy biopsy testing. The convenience sampling method used to select the participants and this subgroup characteristics might limit the ability to generalize the results to the general population. Moreover, the use of FFQ might represent some limitations. Food intake in the previous 18 months of the interview was self-reported by participants with no measure for verification, which might lead to possible recall and information bias. In addition, intake of food and beverage items was assessed without specifying quantities or portion size. However, the variation in portion size between participants is smaller than the variation in the frequency of consumption, which will have a limited effect on the findings. Some medical data were missing or not updated for a group of participants. This could contribute to the final findings. Finally, an inference of causality cannot be generated due to the cross-sectional study design.


*Article* **Intergranular Corrosion and Microstructural Evolution in a Newly Designed Al-6Mg Alloy**

**Kweon-Hoon Choi 1,2, Bong-Hwan Kim 2,\*, Da-Bin Lee 2, Seung-Yoon Yang 2, Nam-Seok Kim 2, Seong-Ho Ha 2, Young-Ok Yoon 2, Hyun-Kyu Lim 2 and Shae-Kwang Kim 2**

**Abstract:** In this work, the microstructure and corrosion behavior of a novel Al-6Mg alloy were investigated. The alloy was prepared by casting from pure Al and Mg+Al2Ca master alloy. The ingots were homogenized at 420 ◦C for 8 h, hot-extruded and cold-rolled with 20% reduction (CR20 alloy) and 50% reduction (CR50 alloy). The CR50 alloy exhibited a higher value of intergranular misorientation due to a higher cold rolling reduction ratio. The average grain sizes were 19 ± 7 μm and 17 ± 9 μm for the CR20 and CR50 alloys, respectively. An intergranular corrosion (IGC) behavior was investigated after sensitization by a nitric acid mass-loss test (ASTM G67). The mass losses of both the CR20 and CR50 alloys were similar at early periods of sensitization, however, the CR20 alloy became more susceptible to IGC as the sensitization time increased. Grain size and β phase precipitation were two critical factors influencing the IGC behavior of this alloy system.

**Keywords:** light alloys; Al-Mg; high-strength; mechanical properties; intergranular corrosion; precipitation