Sumalatda Devi Balamurugan, Aravindhanathan Venkatesan, Arun Radhakrishnan, Gowthamarajan Kuppusamy, Sachin Kumar Singh
Sumalatda Devi Balamurugan1, Aravindhanathan Venkatesan1, Arun Radhakrishnan1, Gowthamarajan Kuppusamy1*, Sachin Kumar Singh2
1Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty Nilgiris, Tamil Nadu, India.
2School of Pharmaceutical Sciences, Lovely Professional University, Punjab 144411, India.
Volume - 14,
Issue - 3,
Year - 2021
Drugs with poor aqueous solubility are still an ongoing challenge in the successful formulation of therapeutic products due to their low oral bioavailability. It reports that over 70% of drugs and active entities are poorly water-soluble compounds. Paracetamol is a BCS class ? drug which has low solubility and high permeability. Hence there is a solubility rate limiting step for paracetamol which is less solubility and ultimately has low bioavailability which instigates formulation challenges because of limited dissolution and/or low permeability. To overcome this solubility rate limiting step the polymorphism of paracetamol can be altered to various polymorphic forms but altering the polymorphic form does not work all the time. Hence it is converted into amorphous form where it has no polymorphic structure. By converting it to an amorphous form higher dissolution, bioavailability can be achieved and hence marketed doses can be reduced. However amorphous product are not stable over a period of time, this study was focused on preparation and stabilization of amorphous product. In this study the paracetamol was PEGylated with PEG 4000 of different concentrations 1:0.5, 1:1, 1:2, 1:4 by melt method. The interactions between paracetamol and polyethylene glycol 4000 in the solid state were probed by FTIR studies and it was proved that there was no incompatibility between paracetamol and PEG 4000. Solubility of the prepared paracetamol-PEG mixture using method C were determined in Millipore Water and it was found that as the ratio increases the solubility also increases. The increase in solubility of such BCS class ? drug will overcome the industrial challenges of formulation and manufacturing expenses.
Cite this article:
Sumalatda Devi Balamurugan, Aravindhanathan Venkatesan, Arun Radhakrishnan, Gowthamarajan Kuppusamy, Sachin Kumar Singh. Preliminary Investigation for Preparing Amorphous Paracetamol. Research J. Pharm. and Tech 2021; 14(3):1487-1492. doi: 10.5958/0974-360X.2021.00264.X
Sumalatda Devi Balamurugan, Aravindhanathan Venkatesan, Arun Radhakrishnan, Gowthamarajan Kuppusamy, Sachin Kumar Singh. Preliminary Investigation for Preparing Amorphous Paracetamol. Research J. Pharm. and Tech 2021; 14(3):1487-1492. doi: 10.5958/0974-360X.2021.00264.X Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2021-14-3-53
1. Trasi NS, et.al. Factors influencing crystal growth rates from undercooled liquids of pharmaceutical compounds. The Journal of Physical Chemistry B. 2014 Aug 7; 118(33): 9974-82.
2. Raza K, et.al. Polymorphism: The Phenomenon Affecting the Performance of Drugs. SOJ Pharm Pharm Sci, 1 (2), 10. Polymorphism: The Phenomenon Affecting the Performance of Drugs. 2014.
3. Poole PH, et.al. Amorphous polymorphism. Computational Materials Science. 1995 Nov 1; 4(4): 373-82.
4. Zimmermann, Boris, and Goran Baranović. "Thermal analysis of paracetamol polymorphs by FT-IR spectroscopies." Journal of Pharmaceutical and Biomedical Analysis 54.2 (2011): 295-302.
5. Baghel S, et.al. Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. Journal of Pharmaceutical Sciences. 2016 Sep 1; 105(9): 2527-44.
6. Hancock BC, et.al. Comparison of the mechanical properties of the crystalline and amorphous forms of a drug substance. International Journal of Pharmaceutics. 2002 Jul 8; 241(1): 73-
7. 85Raw AS, et.al. Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs). Advanced Drug Delivery Reviews. 2004 Feb 23; 56 (3): 397-414
8. Bauer JF. Polymorphism—A Critical Consideration in Pharmaceutical Development, Manufacturing, and Stability. Journal of Validation Technology. 2008 Sep 22; 14(4): 15-23.
9. Hancock BC, Parks M. What is the true solubility advantage for amorphous pharmaceuticals?. Pharmaceutical Research. 2000 Apr 1; 17(4): 397-404.
10. Naumov, D. Yu, et.al. The monoclinic form of acetaminophen at 150K." Acta Crystallographica Section C: Crystal Structure Communications. 54.5 (1998): 653-655.
11. Martino, Piera Di, et al. Molecular mobility of the paracetamol amorphous form. Int. J. Pharm 128 (1996): 1-8.
12. Kauffman, John F, et.al. Tuschel. Raman detected differential scanning calorimetry of polymorphic transformations in acetaminophen. Journal of Pharmaceutical and Biomedical Analysis. 48.5 (2008): 1310-1315.
13. Perlovich, G., et, al. Polymorphism of paracetamol: Relative stability of the monoclinic and orthorhombic phase revisited by sublimation and solution calorimetry. Journal of Thermal Analysis and Calorimetry. 89.3 (2007): 767-774.
14. Burley, Jonathan C., et al. Enforcing Ostwald's rule of stages: Isolation of paracetamol forms III and II. European Journal of Pharmaceutical Sciences. 31.5 (2007): 271-276.
15. Di Martino, P, et.al. Preparation and Physical Characterisation of Forms II and III of Paracetamol. J. Therm. Anal. 1997; 48: 447−458.
16. Qi, S.; Avalle, P. et.al. An investigation into the effects of thermal history on the crystallisation behaviour of amorphous paracetamol. Eur. J. Pharm. Biopharm. 2008; 69: 364−371.
17. Nanubolu, et.al. Investigating the recrystallization behavior of amorphous paracetamol by variable temperature Raman studies and surface Raman mapping. Molecular Pharmaceutics. 9.6 (2012): 1544-1558.
18. Mooter G. The use of amorphous solid dispersions: a formulation strategy to overcome poor solubility and dissolution rate. Drug Discov Today Technol. 2012;9: e79-e85.
19. Eloy J, Marchetti J. Solid dispersions containing ursolic acid in poloxamer 407 and PEG 6000: A comparative study of fusion and solvent methods. Powder Technol. 2014; 253: 98-106.
20. Baghel, et.al. Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. Journal of Pharmaceutical Sciences. 105.9 (2016): 2527-2544.
21. Brazhkin VV, Lyapin AG. High-pressure phase transformations in liquids and amorphous solids. Journal of Physics: Condensed Matter. 2003 Aug 29; 15(36): 6059.