Rhizomes of turmeric (Curcuma longa Linn) is an important ancient edible and medicinal herb used since centuries to treat several diseases, i.e., pain, arthritis, worms, cancer, bruises, eye problems, gastrointestinal problems, and many more. Curcumin (2-6% of the rhizome) is one of the principal bioactive metabolite isolated from the rhizomes of turmeric^[1-3]. Curcumin reported as a potent antioxidant^[5], anti-inflammatory^[6], anti rheumatic^[7], antimicrobial, anti proliferative^[2], anticancer^[8], hepato- and nephro- protectant^[9], myocardial infarction protectant^[10], thrombosis suppressant^[11], and hypoglycemic agent^[12]. However, because of its poor solubility and absorption, high metabolism, along with bad pharmacokinetics, it failed to achieve its efficacy in the treatment of many disorders ^[2,3]. Curcumin nanomedicine (nanocurcumin) is a modified form of curcumin where the particles of curcumin are transformed into nanoparticles that are more soluble, better drug delivery, more targeted to the tissue of interest in the body, and faster treatment compared to curcumin^[4].

Improvement of the solubility and bioavailability of curcumin without any wastage or side effects is a challenge for the scientist throughout the world. Recent studies have revealed that the Trivedi Effect^®-Consciousness Energy Healing Treatment significantly improved the bioavailability of resveratrol, berberine, and 25-hydroxyvitamin D₃ in male Sprague-Dawleyrats^[13-15]. Similarly, many studies on the Trivedi Effect^®claimed to have a significant impact on the physicochemical, spectral, and thermal properties of pharmaceutical/nutraceutical compounds^[16-18]. The Trivedi Effect^® is only scientifically proven phenomenon in which a healer can harness this intelligent energy from the Universal Energy Field and can transmit it anywhere on the planet via the possible mediation of neutrino^[19]. Biofield Energy is a unique para-dimensional electromagnetic field exists around the human body, resulting in continuous emission of energy from the body, which can freely flow between the human and environment^[20]. Several Biofield based Energy Healing Therapies are used and reported with significant benefit against various human disease conditions^[20-22]. Biofield Energy Healing therapies have been recognized worldwide as a Complementary and Alternative Medicine (CAM) health care approach by National Center of Complementary and Integrative Health with other therapies, medicines and practices such as Ayurveda, yoga, Tai Chi, Qi Gong, traditional Chinese herbs and medicines, homeopathy, acupuncture, aromatherapy, chiropractic/osteopathic manipulation, meditation, acupressure, Reiki, healing touch, hypnotherapy, naturopathy, movement therapy, cranial sacral therapy, etc^[23]. The Trivedi Effect^® has been scientifically proven and published outstanding results with research data in the field of materials science^[24,25], chemical science^[26], microbiology^[27,28], biotechnology^[29,30], pharmaceuticals/nutraceuticals^[16-18,31], medical science^[32,33], agriculture^[34,35], etc. It was observed that the Biofield Energy Healing Treatment is an economical approach and has a significant impact on the physicochemical, spectral, and thermal properties of pharmaceuticals and nutraceuticals^[16-19]. Therefore, this experiment has been designed to evaluate the impact of the Trivedi Effect^®-Consciousness Energy Healing Treatment on the physicochemical, structural, and thermal properties of nanocurcumin using sophisticated analytical techniques.

Materials and Methods

Chemicals and Reagents: The test sample nanocurcumin (40%) powder was purchased from Sanat Products Ltd., India, and the other chemicals used in the experiment were available in India.

Consciousness Energy Healing Treatment Strategies: The nanocurcumin powder was equally divided into two parts. One part of nanocurcumin was termed as Biofield Energy Treated sample, which received the Consciousness Energy Healing Treatment (the Trivedi Effect^®) by a renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi (USA) remotely under the standard laboratory conditions for 3 minutes. Besides, the other part of the test sample was termed as the control sample, which did not receive the Trivedi Effect^®-Consciousness Energy Healing Treatment, but was treated by a “sham” healer under the similar laboratory conditions. Where the “sham” healer did not have any understanding about the Biofield Energy. Consequently, both the samples were kept in similar sealed conditions and further characterized using different analytical techniques.

Characterization: The powder X-ray diffraction (PXRD) analysis of nanocurcumin powder sample was performed with the help of PANalytical X’Pert3 Pro[36,37]. The average size of crystallites were calculated using the Scherrer’s formula (1)

G = kλ/βcosθ (1)

Where G = crystallite size in nm, k = equipment constant (0.5), λ = radiation wavelength, β = full-width at half maximum, and θ = Bragg angle^[38].

The particle size distribution (PSD) analysis was done with the help of Malvern Mastersizer 3000 (UK) using the wet method. Ultraviolet-visible spectroscopy (UV-Vis) analysis was carried out using Shimadzu UV-2400PC series, Japan. Fourier transform infrared (FT-IR) spectroscopy of nanocurcumin was performed on Spectrum ES (Perkin Elmer, USA) FT-IR spectrometer. Likewise, the Differential Scanning Calorimetry (DSC) analysis of nanocurcumin was performed with the help of DSC Q200, TA instruments. The Thermal Gravimetric Analysis (TGA) thermo grams of nanocurcumin were performed with the help of TGA Q50 TA instruments^[36,37].

The % change in the above parameters of the Biofield Energy Treated nanocurcumin was calculated compared to the control sample using equation 2:

% Change = [(Treated – Control) / Control] x 100 (2)

Results and Discussion

Powder X-ray Diffraction (XRD) Analysis: The powder XRD diffractograms of both the nanocurcumin samples shown sharp and intense peaks in the diffractograms (Figure 1) indicated that both were crystalline in nature. The diffractogram pattern of the Biofield Energy Treated nanocurcumin was the same, but the relative peak intensities and crystallite sizes were significantly altered compared to the control sample (Table 1).

The PXRD diffractogram of both the samples of nanocurcumin showed the highest peak intensity (100%) at Bragg’s angle (2θ) equal to 17.4° (Table 1, entry 9). The relative peak intensities of the treated nanocurcumin sample were significantly altered in the range from -32.16% to 42.53% compared to the control sample.

Figure 1: Powder XRD diffractograms of the control and treated nanocurcumin.

Table 1: PXRD data for the control and treated nanocurcumin.

The crystallite size of the Biofield Energy Treated sample was significantly altered in the range from -57.12% to 100.09% compared to the control sample. Overall, the average crystallite size of the Biofield Energy Treated sample was significantly decreased by 10.31% compared to the control sample. The experimental PXRD pattern closely matches to the reported literature of nanocurcumin^[39].

Each XRD peak intensity of crystals changes according to their morphologies^[40]. The change in the PXRD pattern provides proof of polymorphic transitions^[41,42]. Changes in the relative peak intensities and crystallite size of PXRD peaks indicated that the crystal morphology of the Biofield Energy Treated nanocurcumin was altered compared to the control sample. Thus, it can be assumed that due to the Trivedi Effect^®-Biofield Energy Healing Treatment on the nanocurcumin crystals probably introduced a new polymorphic form. These polymorphic forms of pharmaceuticals have the significant effects on the drug performance, such as bioavailability, therapeutic efficacy, and toxicity, because of their thermodynamic and physicochemical properties like melting point, energy, stability, and especially solubility, are different (probably an improvement) from the original form^[43,44].

Particle Size Distribution (PSD) Analysis: Particle size values and surface area of both the nanocurcumin samples were investigated, and the results are presented in Table 2. The particle size values in the Biofield Energy Treated nanocurcumin at d₁₀, d₅₀, d₉₀, and D(4,3) was decreased by 0.14%, 2.20%, 8.02%, and 4.90%, respectively compared to the control sample. Therefore, the surface area of the Biofield Energy Treated sample (426.40m²/g) was increased by 1.94% compared with the control sample (418.30m²/g).

Table 2: Particle size values and surface area of the control and treated nanocurcumin.

The particle size and surface area are the parameters which play animportant role in the solubility, absorption, dissolution, and bioavailability of the nutraceutical and pharmaceutical formulations^[45-47]. In this case, the particle sizes of the Trivedi Effect^®-Energy of Consciousness Healing Treated nanocurcumin were reduced; hence, the surface area was increased. Therefore, it can be assumed that the solubility of the Biofield Energy Treated nanocurcumin as well as the dissolution rate and bioavailability would be increased in the formulation^[47,48].

Fourier Transform Infrared (FT-IR) Spectroscopy: The control and Biofield Energy Treated nanocurcumin samples were investigated by FT-IR spectroscopy (Figure 2). The FT-IR spectrum of nanocurcumin showed characteristic absorption bands near 3391 cm^-1 in control and 3379 cm^-1 in the Biofield Energy Treated sample represent the –O-H stretching vibration. While the 2939 cm^-1 in the control and 2936 cm^-1 in the Biofield Energy Treated sample represent sp³ –C–H stretching. Very intensive peaks near 1628 cm^-1 in the spectra of nanocurcumin control and Biofield Energy Treated samples were the results of asymmetric and symmetric vibrations of C=O of a carbonyl group. The band at 1510 cm^-1 could be assigned to –C=C– in the ring while the broad band near 1429 corresponds to –CH₃ deformations and the bands between 1027 and 1281 cm^-1 originate from –C–O– stretching vibrations observed in both the spectra. The band between 856 and 812 cm^-1 originates from –C–H bending vibrations in both the control and Biofield Energy Treated samples of nanocurcumin. The detailed experimental vibration spectra of curcumin were similar to that of earlier reported literature^[49,50]. Since, both the spectra have very close IR bands of nanocurcumin indicated that there was no significant alteration in the structural properties of the Biofield Energy Treated sample compared to the control sample.

Figure 2: FT-IR spectra of the control and treated nanocurcumin.

Ultraviolet-visible Spectroscopy (UV-Vis) Analysis:

The UV-visible spectra of the control and Biofield Energy Treated nanocurcumin are shown in Figure 3. The UV spectrum of both the control and Biofield Energy Treated samples showed the maximum absorbance at 416 nm (λ_max). The peak at 416 nm was showed a minor shift of absorbance maxima from 3.2364 in control to 3.3122 in Biofield Energy Treated sample. The evolution of absorption peak at 416 nm for the π–π* transitions of nanocurcumin in methanol, as well as the decreasing intensity, designate a change in the tautomeric form of the keto–enol–enolate group in nanocurcumin. The broadening of the absorption band at 416 nm was caused due to the aggregation of the nanocrystals^[49]. The analysis revealed that the electronic transitions between the highest occupied molecular orbital and lowest unoccupied molecular orbital remained same in control, and Biofield Energy Treated nanocurcumin samples.

Figure 3: UV-Vis spectra of the control and treated nanocurcumin.

Differential Scanning Calorimetry (DSC) Analysis

The DSC thermograms of the control and Biofield Energy Treated samples of nanocurcumin exhibited two sharp endothermic peaks due to evaporation of moisture from the sample and melting temperature of nanocurcumin (Figure 4). The vaporization and melting temperature of the Biofield Energy Treated sample were slightly increased by 0.17% and 0.08%, respectively compared with the control sample. The latent heat of vaporization (ΔH_vaporization) in the Biofield Energy Treated nanocurcumin (96.68 J/g) was significantly increased by 32.80% compared to the control (72.80 J/g) sample (Table 3). Similarly, the latent heat of fusion (ΔH_fusion) in the Biofield Energy Treated nanocurcumin (43.61 J/g) was significantly increased by 20.34% compared to the control sample (36.24 J/g) (Table 3). The experimental data were well correlated with the published literature data ^[39]. The DSC data concluded that the thermal stability of the Biofield Energy Treated nanocurcumin was increased compared to the control sample.

Table 3: DSC data for the control and treated samples of nanocurcumin.

Figure 4: DSC thermograms of the control and treated nanocurcumin.

Thermal Gravimetric Analysis (TGA): The TGA thermograms of the control and Biofield Energy Treated nanocurcumin exhibited four steps of thermal degradation (Figure 5). The experimental data are well correlated with the published literature data^[51]. The % weight loss in the 1^st step was increased by 7.96%, while in the 2^nd, 3^rd, and 4^th steps of degradation it was decreased by 2.60%, 3.32%, 0.30%, and 1.14%, respectively in the Biofield Energy Treated nanocurcumin compared with the control sample (Table 4). The total weight loss in the Biofield Energy Treated nanocurcumin (60.54) was decreased by 1.14% compared with the control sample (61.24).

Figure 5: TGA thermograms of the control and treated nanocurcumin.

The DTG thermograms of the control and Biofield Energy Treated nanocurcumin revealed maximum thermal degradation temperature (T_max) at 308.42°C and 309.84°C, respectively (Figure 7). The T_max of the treated nanocurcumin was increased by 0.46% compared with the control sample (Table 4). Overall, thermal analysis (DSC, TGA/DTG) concluded that the thermal stability of the Biofield Energy Treated nanocurcumin was increased compared to the control sample.

Figure 6: DTG thermograms of the control and treated nanocurcumin.

Conclusion

Overall experimental results revealed that the Trivedi Effect^®-Consciousness Energy Healing Treatment have the significant impact on the physicochemical and thermal properties of nanocurcumin. The powder XRD relative peak intensities and crystallite sizes of the Biofield Energy Treated sample were significantly altered ranging from -32.16% to 42.53% and from -57.12% to 100.09%, respectively compared to the control sample. However, the average crystallite size of the Biofield Energy Treated nanocurcumin was significantly decreased by 10.31% compared with the control sample. The particle sizes of the Biofield Energy Treated sample were decreased by 0.14% (d₁₀), 2.20% (d₅₀), 8.02% (d₉₀), and 4.90% {D (4,3)} compared with the control sample. Thus, the surface area of the treated nanocurcumin was increased by 1.94% compared with the control sample. The vaporization and melting temperature of the Biofield Energy Treated sample were slightly increased compared with the control sample. However, the latent heat of vaporization and latent heat of fusion in the Biofield Energy Treated nanocurcumin was significantly improved by 32.80% and 20.34%, respectively compared with the control sample. The TGA thermograms of both the samples exhibited four steps of thermal degradation. The total weight loss was decreased, and T_max was increased in the Biofield Energy Treated nanocurcumin compared with the control sample. Overall, the thermal analysis indicated that the thermal stability of the Biofield Energy Treated nanocurcumin was increased compared to the control sample. The Trivedi Effect^®-Consciousness Energy Healing Treatment might lead to the production of a new polymorphic form of nanocurcumin, which would be better soluble, bio available, and thermally more stable compared with the untreated sample. Thus, the treated nanocurcumin would be advantageous in designing better nutraceutical/pharmaceutical formulations as an antioxidant, anti-inflammatory, anti rheumatic, antimicrobial, anti proliferative, anticancer, hepato- and nephro-protectant, myocardial infarction protectant, thrombosis suppressant, hypoglycemic agent, eye problems, gastrointestinal problems, etc.

Acknowledgements

The authors are grateful to GVK Biosciences Pvt. Ltd., Trivedi Science, Trivedi Global, Inc., and Trivedi Master Wellness for their assistance and support during this work.

References

1. 1. Ravichandran, R. Pharmacokinetic study of nanoparticulate curcumin: Oral formulation for enhanced bioavailability. (2013) J BiomaterNanobiotechnol 4: 291-299.

   Pubmed│Crossref│Others

2. 2. Anand, P., Kunnumakkara, A.B., Newman, R.A., et al. (2007) Bioavailability of curcumin: Problems and promises. Mol Pharmaceutics 4: 807-818.

   Pubmed│Crossref│Others

3. 3. Itokawa, H., Shi, Q., Akiyama, T., et al. Recent advances in the investigation of curcuminoids. (2008) Chinese Medicine 3:11.

   Pubmed│Crossref│Others

4. 4. Bisht, S., Feldmann, G., Soni, S., et al. Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): A novel strategy for human cancer therapy. (2007) J Nanobiotechnology 5: 3.

   Pubmed│Crossref│Others

5. 5. Jayaprakasha, G.K., Rao, L.J., Sakariah, K.K. Antioxidant activities of curcumin, demethoxycurcumin and bis demethoxy curcumin. (2006) Food Chem 98: 720-724.

   Pubmed│Crossref│Others

6. 6. Srimal, R.C., Dhawan, B.N. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. (1973) J Pharm Pharmacol 25: 447-452.

   Pubmed│Crossref│Others

7. 7. Deodhar, S.D., Sethi, R., Srimal, R.C. Preliminary study onantirheumatic activity of curcumin (diferuloyl methane). (1980) Indian J Med Res 71: 632-634.

   Pubmed│Crossref│Others

8. 8. Mahady, G.B., Pendland, S.L., Yun, G, et al. Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacterpylori, a group 1 carcinogen. (2002) Anticancer Res 22: 4179-4181.

   Pubmed│Crossref│Others

9. 9. Venkatesan, N., Punithavathi, D., Arumugam, V. Curcumin prevents adriamycin nephrotoxicity in rats. (2000) Br J Pharmacol 129: 231-234.

   Pubmed│Crossref│Others

10. 10. Nirmala, C., Puvanakrishnan, R. Protective role of curcuminagainst isoproterenol induced myocardial infarction in rats. (1996) Mol Cell Biochem 159: 85-93.

    Pubmed│Crossref│Others

11. 11. Srivastava, R., Dikshit, M., Srimal, R.C., et al. Anti thrombotic effect of curcumin. (1985) Thromb Res 40: 413-417.

    Pubmed│Crossref│Others

12. 12. Babu, P.S., Srinivasan, K. Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats. (1997) Mol Cell Biochem166: 169-175.

    Pubmed│Crossref│Others

13. 13. Branton, A., Jana, S. The influence of energy of consciousness healing treatment on low bioavailable resveratrol in male Sprague Dawley rats. (2017) Int J Clin Developmental Anat 3: 9-15.

    Pubmed│Crossref│Others

14. 14. Branton, A., Jana, S. The use of novel and unique biofield energy healing treatment for the improvement of poorly bioavailable compound, berberine in male Sprague Dawley rats. (2017) Am J Clin Experi Med5: 138-144.

    Pubmed│Crossref│Others

15. 15. Branton, A., Jana, S. Effect of The biofield energy healing treatment on the pharmacokinetics of 25-hydroxyvitamin D₃ [25(OH)D₃] in rats after a single oral dose of vitamin D₃. (2017) Am J Pharmaand Phytother 2: 11-18.

    Pubmed│Crossref│Others

16. 16. Trivedi, M.K., Branton, A., Trived, D., et al. Effect of the energy of consciousness (The Trivedi Effect^{®) on physicochemical, thermal, structural, and behavioral properties of magnesium gluconate. (2017) ChemBiomo Eng 2: 113-123.}

    Pubmed│Crossref│Others

17. 17. Trivedi, M.K., Branton, A., Trivedi. D., et al. Impact of consciousness energy healing treatment (The Trivedi Effect^®) on physical, spectroscopic, and thermal properties of Withania somnifera (ashwagandha) root extract. (2017) Int J Food Sci Biotech 2: 6-15.

    Pubmed│Crossref│Others

18. 18. Trivedi, M.K., Branton, A., Trivedi, D., et al. Evaluation of the Trivedi Effect^®- Energy of Consciousness Energy Healing Treatment on the physical, spectral, and thermal properties of zinc chloride. (2017) Am J Life Sci 5: 11-20.

    Pubmed│Crossref│Others

19. 19. Trivedi, M.K., Mohan, T.R.R. Biofield energy signals, energy transmission and neutrinos. (2016) American Journal of Modern Physics 5: 172-176.

    Pubmed│Crossref│Others

20. 20. Rubik, B., Muehsam, D., Hammerschlag, R., et al. Biofield Science and Healing: History, Terminology, and Concepts. (2015) Glob Adv Health Med 4: 8-14.

    Pubmed│Crossref│Others

21. 21. Warber, S.L., Cornelio, D., Straughn,, J., et al. Biofield energy healing from the inside. (2004) J Altern Complement Med 10: 1107-1113.

    Pubmed│Crossref│Others

22. 22. Movaffaghi, Z., Farsi, M. Biofield therapies: Biophysical basis and biological regulations? (2009) Complement TherClinPr 15: 35-37.

    Pubmed│Crossref│Others

23. 23. Barnes, P.M., Bloom, B., Nahin, R.L. Complementary and alternative medicine use among adults and children: United States, 2007. (2008) Natl Health Stat Report 12: 1-23.

    Pubmed│Crossref│Others

24. 24. Trivedi, M.K., Tallapragada, R.M. A transcendental to changing metal powder characteristics. (2008) Metal Powder Report 63: 22-28.

    Pubmed│Crossref│Others

25. 25. Trivedi, M.K., Tallapragada, R.M. Effect of superconsciousness external energy on the atomic, crystalline and powder characterisitics of “carbon allotrope powders”. (2009) Materials Research Innovations 13: 473-480.

    Pubmed│Crossref│Others

26. 26. Trivedi, M.K., Branton, A., Trivedi, D., et al. Mass spectrometric analysis of isotopic abundance ratio in biofield energy treated thymol. (2016) Frontiers in Applied Chemistry 1: 1-8.

    Pubmed│Crossref│Others

27. 27. Trivedi, M.K., Branton, A., Trivedi, D., et al. Antibiogram typing of biofield treated multidrug resistant strains of Staphylococcus species. (2015) American Journal of Life Sciences 3: 369-374.

    Pubmed│Crossref│Others

28. 28. Trivedi, M.K,, Branton. A., Trivedi, D., et al. Antibiogram, biochemical reactions and genotyping characterization of biofield treated Staphylococcus aureus. (2015) American Journal of BioScience 3: 212-220.

    Pubmed│Crossref│Others

29. 29. Trivedi, M.K., Patil, S., Shettigar, H., et al. In vitro evaluation of biofield treatment on cancer biomarkers involved in endometrial and prostate cancer cell lines. (2015) J Cancer SciTher 7: 253-257.

    Pubmed│Crossref│Others

30. 30. Trivedi, M.K., Branton, A., Trivedi, D., et al. Evaluation of plant growth regulator, immunity and DNA fingerprinting of biofield energy treated mustard seeds (Brassica juncea). (2015) Agriculture, Forestry and Fisheries 4: 269-274.

    Pubmed│Crossref│Others

31. 31. Trivedi, M.K., Branton, A., Trivedi, D., et al. Fourier transform infrared and ultraviolet-visible spectroscopic characterization of biofield treated salicylic acid and sparfloxacin. (2015) Nat Prod Chem Res 3: 186.

    Pubmed│Crossref│Others

32. 32. Trivedi, M.K., Patil, S., Shettigar, H., et al. The potential impact of biofield treatment on human brain tumor cells: A time-lapse video microscopy. (2015) J IntegrOncol 4: 141.

    Pubmed│Crossref│Others

33. 33. Trivedi, M.K., Patil, S., Shettigar, H., et al. In vitro evaluation of biofield treatment on cancer biomarkers involved in endometrial and prostate cancer cell lines. (2015) J Cancer SciTher 7: 253-257.

    Pubmed│Crossref│Others

34. 34. Trivedi, M.K., Branton, A., Trivedi, D., et al. Agronomic characteristics, growth analysis, and yield response of biofield treated mustard, cowpea, horse gram, and groundnuts. (2015) Int J Genet Geno 3: 74-80.

    Pubmed│Crossref│Others

35. 35. Trivedi, M.K., Branton, A., Trivedi, D., et al. Evaluation of plant growth, yield and yield attributes of biofield energy treated mustard (brassica juncea) and chick pea (CicerArietinum) Seeds. (2015) Agri, Foresta Fisheries 4: 291-295.

    Pubmed│Crossref│Others

36. 36. Trivedi, M.K., Sethi, K.K., Panda, P., et al. Physicochemical, thermal and spectroscopic characterization of sodium selenate using XRD, PSD, DSC, TGA/DTG, UV-vis, and FT-IR. (2017) Marmara Pharmaceutical 21/2: 311-318.

    Pubmed│Crossref│Others

37. 37. Trivedi, M.K., Sethi, K.K., Panda, P., et al. In-depth investigation on physicochemical and thermal properties of magnesium (II) gluconate using spectroscopic and thermo analytical techniques. (2017) J Pharma Analy 7: 332-337.

    Pubmed│Crossref│Others

38. 38. Langford, J.I., Wilson, A.J.C. Scherrer after sixty years: A survey and some new results in the determination of crystallite size. (1978) J ApplCryst 11: 102-113.

    Pubmed│Crossref│Others

39. 39. Zhao, Z., Xie, M., Li, Y., et al. Formation of curcumin nanoparticles via solution-enhanced dispersion by supercritical CO_{2. (2015) Int J Nanomedicine10: 3171-3181.}

    Pubmed│Crossref│Others

40. 40. Inoue, M., Hirasawa, I. The relationship between crystal morphology and XRD peak intensity on CaSO_{4.2H2O. (2013) J Crystal Growth 380: 169-175.}

    Pubmed│Crossref│Others

41. 41. Raza, K., Kumar, P., Ratan, S., et al. Polymorphism: The phenomenon affecting the performance of drugs. (2014) SOJ Pharm PharmSci 1: 10.

    Pubmed│Crossref│Others

42. 42. Brittain, H.G. Polymorphism in pharmaceutical solids in Drugs and Pharmaceutical Sciences. (2009).

    Pubmed│Crossref│Others

43. 43. Censi, R., Martino, P.D. Polymorph impact on the bioavailability and stability of poorly soluble drugs. (2015) Molecules 20: 18759-18776.

    Pubmed│Crossref│Others

44. 44. Blagden, N., de Matas, M., Gavan, P.T., et al. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. (2007) Adv Drug Deliv Rev 59(7): 617-630.

    Pubmed│Crossref│Others

45. 45. Chereson, R. Bioavailability, bioequivalence, and drug selection.

    Pubmed│Crossref│Others

46. 46. Khadka, P., Ro, J., Kim, H., et al. (2014) Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm Sci 9: 304-316.

    Pubmed│Crossref│Others

47. 47. Mosharrof, M., Nystrӧm, C. The effect of particle size and shape on the surface specific dissolution rate of microsized practically insoluble drugs. (1995) Int J Pharm 122(1-2): 35-47.

    Pubmed│Crossref│Others

48. 48. Buckton, G., Beezer, A.E. The relationship between particle size and solubility. (1992) Int J Pharmaceutics 82: R7-R10.

    Pubmed│Crossref│Others

49. 49. Marković, Z.M., Prekodravac, J.R., Tošić, D.D., et al. Facile synthesis of water-soluble curcumin nanocrystals. (2015) J Serb ChemSoc 80: 63-72.

    Pubmed│Crossref│Others

50. 50. Kolev, T.M., Velcheva, E.A., Stamboliyska, B.A., et al. DFT and experimental studies of the structure and vibrational spectra of curcumin. (2005) Int J Quantum Chem102: 1069.

    Pubmed│Crossref│Others

51. 51. Mathew, A., Fukuda, T., Nagaoka, Y., et al. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. (2012) PLoS One 7(3): e32616.

    Pubmed│Crossref│Others