Evaluation and Preparation of Crystal Modifications of Artesunate: In vivo Studies
Five crystal modifications of water insoluble
artesunate were generated by recrystallizing it from various solvents
with improved physicochemical properties. These generated crystal
forms were characterized to select the most potent and soluble form.
SEM of all the forms showed changes in external shape leading them
to be different morphologically. DSC thermograms of Form III and
Form V showed broad endotherm peaks at 83.04oC and 76.96oC prior
to melting fusion of drug respectively. Calculated weight loss in TGA
revealed that Form III and Form V are methanol and acetone solvates
respectively. However, few additional peaks were appeared in XRPD
pattern in these two solvate forms. All forms exhibit exothermic
behavior in buffer and two solvates display maximum ease of
molecular release from the lattice. Methanol and acetone solvates
were found to be most soluble forms and exhibited higher
antimalarial efficacy showing higher survival rate (83.3%) after 30
days.
<p>[1] L. Borka., “Review on crystal polymorphism of substances, in the
European pharmacoepiea,” Pharm Acta Helv., vol. 66, no.1, pp. 16–22,
1991.
[2] S. Mirza, I. Miroshnyk, J. Heinämäki, L. Christiansen, M. Karjalainen,
and J. Yliruusi, “Influence of Solvents on the Variety of Crystalline
Forms of Erythromycin,” AAPS PharmSci., vol. 5, no. 2, pp. 39–47,
2003.
[3] N. Rasenack, B. W. Muller, “Properties of Ibuprofen crystallized under
various conditions: A comparative study” Drug Dev Ind Pharm.., vol.
28, no.9, pp. 278-289, 2002.
[4] F. Jamali, A. G. Mitchell, “The recrystallization and dissolution of
acetylsalicylic acid,” Acta Pharm Suec.vol. 4, pp. 343-352, 1973.
[5] Jozwiakowski MJ, Nguyen NA, Sisco JM, Spancake CW. Solubility
behavior of lamivudine crystal forms in recrystallization solvents. J
Pharm Sci. 1996; 85(2): 193-199.
[6] Chemburkar SR, Bauer J, Deming K, Spiwek H, Patel K, Morris J, et al.
Dealing with the impact of ritonavir polymorphs on the late stages of
bulk drug process development. Org Process Res Dev. 2000; 4: 413-417.
[7] Byrn SR, Pfeiffer RR, Stowell JG. Solid-State Chemistry of Drugs,
SSCI, West Lafayette, IN, 1999.
[8] Mohanachandran PS, Sindhumol PG, Kiran T. Enhancement of
solubility and dissolution rate: an overview. International Journal of
Comprehensive Pharmacy. Pharmacie Globale. 2010; 4 (11): 1-10.
[9] Javadzadeh Y, Hamedeyazdan S, Asnaashari S. Recrystallization of
Drugs : Significance on Pharmaceutical Processing, Recrystallization,
Prof. Krzysztof Sztwiertnia (Ed.), InTech, 2010;
http://www.intechopen.com/books/recrystallization/recrystallizationofdrugs-
significance-on-pharmaceutical-processing. ISBN: 978-953-51-
0122-2,
[10] Morris KR, Griesser UJ, Eckhardt CJ, Stowell JG. Theoretical
approaches to physical transformations of active pharmaceutical
ingredients during manufacturing processes. Adv Drug Deliv Rev. 2001;
48: 91–114.
[11] Khan GM, Jiabi Z. Preparation, characterization & evaluation of
physicochemical properties of different crystalline forms of Ibuprofen.
Drug Dev Ind Pharm. 1998; 24 (5):463 – 471.
[12] Yeo S, Kim M, Lee J. Recrystallization of sulfathiazole &
chlorpropamide using supercritical fluid antisolvent process. The Journal
of Supercritical Fluids. 2003; 25(2): 143-154.
[13] Urbanetz NA, Lippold BC. Solid Dispersion of nimodipne and
polyoxyethene an additive prevents the drug from
recrystalization.www.eurostar-science.org.
[14] Kawashima Y, Handa T, Takeuchi H, Okumura M, Katou H, Nagata O.
Crystal modification of phenytoin with polyethylene glycol for
improving mechanical strength, dissolution rate and bioavailability by a
spherical crystallization technique. Chem Pharm Bull (Tokyo). 1986;
34(8): 3376-3383.
[15] Carino SR, Sperry DC, Hawley M. Relative bioavailability estimation of
carbamazepine crystal forms using an artificial stomach-duodenum
model. J Pharm Sci. 2006; 95(1):116-125.
[16] Sen D, Banerjee A, Ghosh AK, Chatterjee TK. Synthesis and
antimalarial evaluation of some 4-quinazolinone derivatives based on
febrifugine. Journal of Advanced Pharmaceutical Technology &
Research. 2010; 1(4):401-405. DOI: 10.4103/0110-5558.76439
[17] Mohanraj V, Chen, Y. Nanoparticles-a review. Tropical Journal of
Pharmaceutical Research. 2007; 5 (1): 561-573.
[18] Pan Y, Liu Y, Zeng G, Zhao L, Lai Z. Rapid synthesis of zeolitic
imidazolate framework-8 (ZIF-8) nanocrystals in an aqueous system.
Chem Commun (Camb). 2011; 47(7): 2071-3. doi: 10.1039/c0cc05002d.
[19] Cravillon J, Mu nzer S, Lohmeier SJ, Feldhoff A, Huber K, Wiebcke M.
Rapid Room-Temperature Synthesis and Characterization of
Nanocrystals of a Prototypical Zeolitic Imidazolate Framework.
Chemistry of Materials. 2009; 21 (8): 1410-1412.
[20] Yellela SRK. Pharmaceutical technologies for enhancing oral
bioavailability of poorly soluble drugs. Journal of Bioequivalence &
Bioavailability. 2010; 2(2): 28–36.
[21] Kumar A, Sahoo SK, Padhee K, Kochar PS, Sathapathy A, Pathak N.
Review on solubility enhancement techniques for hydrophobic
drugs. Pharmacie Globale. 2011; 3(3): 001–007.
[22] Rinaki E, Valsami G, and Macheras P. Quantitative Biopharmacuetics
Classification System; the central role of dose/solubility ratio. Pharm
Res. 2003; 20: 1917.
[23] Chadha R, Kashid N, Jain DV. Characterization and quantification of
amorphous content in some selected parenteral cephalosporins by
calorimetric method. J Therm Anal Calorim. 2005; 81: 277-284.
[24] Chadha R, Kashid N, Jain DV. Microcalorimetric evaluation of the in
vitro compatibility of amoxicillin/clavulanic acid and
ampicillin/sulbatam with ciprofloxacin. J Pharm Biomed Anal. 2004; 36:
295-307.
[25] Giron D, Goldbronn C, Mutz M, Pfeffer S, Piechon P, Schwab P. Solid
state characterization of pharmaceutical hydrates. J Therm Anal. 2002;
68:453–65. doi: 10.1023/A:1016031517430.
[26] Heng JY, Bismarck A, Williams DR. Anisotropic surface chemistry of
crystalline pharmaceutical solids. AAPS PharmSciTech. 2006; 7(4):
E12–E20.</p>
<p>[1] L. Borka., “Review on crystal polymorphism of substances, in the
European pharmacoepiea,” Pharm Acta Helv., vol. 66, no.1, pp. 16–22,
1991.
[2] S. Mirza, I. Miroshnyk, J. Heinämäki, L. Christiansen, M. Karjalainen,
and J. Yliruusi, “Influence of Solvents on the Variety of Crystalline
Forms of Erythromycin,” AAPS PharmSci., vol. 5, no. 2, pp. 39–47,
2003.
[3] N. Rasenack, B. W. Muller, “Properties of Ibuprofen crystallized under
various conditions: A comparative study” Drug Dev Ind Pharm.., vol.
28, no.9, pp. 278-289, 2002.
[4] F. Jamali, A. G. Mitchell, “The recrystallization and dissolution of
acetylsalicylic acid,” Acta Pharm Suec.vol. 4, pp. 343-352, 1973.
[5] Jozwiakowski MJ, Nguyen NA, Sisco JM, Spancake CW. Solubility
behavior of lamivudine crystal forms in recrystallization solvents. J
Pharm Sci. 1996; 85(2): 193-199.
[6] Chemburkar SR, Bauer J, Deming K, Spiwek H, Patel K, Morris J, et al.
Dealing with the impact of ritonavir polymorphs on the late stages of
bulk drug process development. Org Process Res Dev. 2000; 4: 413-417.
[7] Byrn SR, Pfeiffer RR, Stowell JG. Solid-State Chemistry of Drugs,
SSCI, West Lafayette, IN, 1999.
[8] Mohanachandran PS, Sindhumol PG, Kiran T. Enhancement of
solubility and dissolution rate: an overview. International Journal of
Comprehensive Pharmacy. Pharmacie Globale. 2010; 4 (11): 1-10.
[9] Javadzadeh Y, Hamedeyazdan S, Asnaashari S. Recrystallization of
Drugs : Significance on Pharmaceutical Processing, Recrystallization,
Prof. Krzysztof Sztwiertnia (Ed.), InTech, 2010;
http://www.intechopen.com/books/recrystallization/recrystallizationofdrugs-
significance-on-pharmaceutical-processing. ISBN: 978-953-51-
0122-2,
[10] Morris KR, Griesser UJ, Eckhardt CJ, Stowell JG. Theoretical
approaches to physical transformations of active pharmaceutical
ingredients during manufacturing processes. Adv Drug Deliv Rev. 2001;
48: 91–114.
[11] Khan GM, Jiabi Z. Preparation, characterization & evaluation of
physicochemical properties of different crystalline forms of Ibuprofen.
Drug Dev Ind Pharm. 1998; 24 (5):463 – 471.
[12] Yeo S, Kim M, Lee J. Recrystallization of sulfathiazole &
chlorpropamide using supercritical fluid antisolvent process. The Journal
of Supercritical Fluids. 2003; 25(2): 143-154.
[13] Urbanetz NA, Lippold BC. Solid Dispersion of nimodipne and
polyoxyethene an additive prevents the drug from
recrystalization.www.eurostar-science.org.
[14] Kawashima Y, Handa T, Takeuchi H, Okumura M, Katou H, Nagata O.
Crystal modification of phenytoin with polyethylene glycol for
improving mechanical strength, dissolution rate and bioavailability by a
spherical crystallization technique. Chem Pharm Bull (Tokyo). 1986;
34(8): 3376-3383.
[15] Carino SR, Sperry DC, Hawley M. Relative bioavailability estimation of
carbamazepine crystal forms using an artificial stomach-duodenum
model. J Pharm Sci. 2006; 95(1):116-125.
[16] Sen D, Banerjee A, Ghosh AK, Chatterjee TK. Synthesis and
antimalarial evaluation of some 4-quinazolinone derivatives based on
febrifugine. Journal of Advanced Pharmaceutical Technology &
Research. 2010; 1(4):401-405. DOI: 10.4103/0110-5558.76439
[17] Mohanraj V, Chen, Y. Nanoparticles-a review. Tropical Journal of
Pharmaceutical Research. 2007; 5 (1): 561-573.
[18] Pan Y, Liu Y, Zeng G, Zhao L, Lai Z. Rapid synthesis of zeolitic
imidazolate framework-8 (ZIF-8) nanocrystals in an aqueous system.
Chem Commun (Camb). 2011; 47(7): 2071-3. doi: 10.1039/c0cc05002d.
[19] Cravillon J, Mu nzer S, Lohmeier SJ, Feldhoff A, Huber K, Wiebcke M.
Rapid Room-Temperature Synthesis and Characterization of
Nanocrystals of a Prototypical Zeolitic Imidazolate Framework.
Chemistry of Materials. 2009; 21 (8): 1410-1412.
[20] Yellela SRK. Pharmaceutical technologies for enhancing oral
bioavailability of poorly soluble drugs. Journal of Bioequivalence &
Bioavailability. 2010; 2(2): 28–36.
[21] Kumar A, Sahoo SK, Padhee K, Kochar PS, Sathapathy A, Pathak N.
Review on solubility enhancement techniques for hydrophobic
drugs. Pharmacie Globale. 2011; 3(3): 001–007.
[22] Rinaki E, Valsami G, and Macheras P. Quantitative Biopharmacuetics
Classification System; the central role of dose/solubility ratio. Pharm
Res. 2003; 20: 1917.
[23] Chadha R, Kashid N, Jain DV. Characterization and quantification of
amorphous content in some selected parenteral cephalosporins by
calorimetric method. J Therm Anal Calorim. 2005; 81: 277-284.
[24] Chadha R, Kashid N, Jain DV. Microcalorimetric evaluation of the in
vitro compatibility of amoxicillin/clavulanic acid and
ampicillin/sulbatam with ciprofloxacin. J Pharm Biomed Anal. 2004; 36:
295-307.
[25] Giron D, Goldbronn C, Mutz M, Pfeffer S, Piechon P, Schwab P. Solid
state characterization of pharmaceutical hydrates. J Therm Anal. 2002;
68:453–65. doi: 10.1023/A:1016031517430.
[26] Heng JY, Bismarck A, Williams DR. Anisotropic surface chemistry of
crystalline pharmaceutical solids. AAPS PharmSciTech. 2006; 7(4):
E12–E20.</p>
@article{"International Journal of Medical, Medicine and Health Sciences:57638", author = "S. Gupta and R. Chadha", title = "Evaluation and Preparation of Crystal Modifications of Artesunate: In vivo Studies", abstract = "Five crystal modifications of water insoluble
artesunate were generated by recrystallizing it from various solvents
with improved physicochemical properties. These generated crystal
forms were characterized to select the most potent and soluble form.
SEM of all the forms showed changes in external shape leading them
to be different morphologically. DSC thermograms of Form III and
Form V showed broad endotherm peaks at 83.04oC and 76.96oC prior
to melting fusion of drug respectively. Calculated weight loss in TGA
revealed that Form III and Form V are methanol and acetone solvates
respectively. However, few additional peaks were appeared in XRPD
pattern in these two solvate forms. All forms exhibit exothermic
behavior in buffer and two solvates display maximum ease of
molecular release from the lattice. Methanol and acetone solvates
were found to be most soluble forms and exhibited higher
antimalarial efficacy showing higher survival rate (83.3%) after 30
days.
", keywords = "Artesunate, Crystal modifications, in vivo studies,
Recrystallization.", volume = "7", number = "7", pages = "376-7", }
