PREPARATION, SOLID STATE CHARACTERISATION OF PACLITAXEL AND NARINGEN COCRYSTALS WITH IMPROVED SOLUBILITY
DOI:
https://doi.org/10.22159/ijap.2016v8i4.14251Keywords:
Paclitaxel, Cocrystals, Solid state characterization, NaringinAbstract
Objective: The objective of the present study is to prepare a better form of paclitaxel cocrystal with improved solubility. Paclitaxel (PTX) is a class-4 drug; this drug has low aqueous solubility and high affinity for P-gp. Available formulation are IV based and using our research work with advantages of co-crystal technology towards the enhancement of paclitaxel solubility and thereby its bioavailability (1) and also to improve the patient compliance.
Methods: Naringen was selected based on their chemical nature and its ability to inhibit P-gp, solvent assisted grinding method used to prepare the cocrystals, and prepared cocrystals were subjected to solid state characterization to determine the crystal structure of the cocrystals, as this can provide significant new insights into how the drug and coformer interact, and thereby provide an excellent crystal engineering guide to new cocrystals, potentially with improved properties. Instruments like Fourier transform infrared spectroscopy(FTIR), differential scanning calorimetry, X-ray powder diffraction will be used to determine their stability and any phase transformations (including decomposition) which they might undergo as a function of temperature.
Results: Principle involved in the formation of cocrystal is hydrogen bonding between C=O and N-H group of drug and COOH groups of coformers, which is confirmed by FTIR data and DSC experiments were carried out to study the melting point and heat of enthalpy of the cocrystals. Results clearly shows that the melting point of the cocrystals was increased which confirms the formation of cocrystals. The drug and formation of cocrystals are explained by the X-ray powder diffraction patterns. The PXRD patterns of the pure drug showed sharp, well-defined peaks(spectrum attached) and cocrystals PXRD patterns shows that there is a significant difference in the entire diffraction pattern, changes in peak locations with respect to pure drug indicates a change in the arrangement of molecules, hence confirms the development of new crystalline phase.
Conclusion: The results obtained from the above experiments clearly shows the formation of cocrystals with improved solubility.
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References
Choi JS, Jo BW, Kim YC. Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin. Eur J Pharm Biopharm 2006; 57:313-8.
Qiao N, Li M, Schlindwein W, Malek N, Davies A, Trappitt G. Pharmaceutical cocrystals: an overview. Int J Pharm 2011;419:1-11.
Huang NC. Engineering cocrystal solubility and stability via ionization and micellar solubilization: University of Michigan; 2011.
Yadav A, Shete A, Dabke A, Kulkarni P, Sakhare S. Co-crystals: a novel approach to modify physicochemical properties of active pharmaceutical ingredients. Indian J Pharm Sci 2009;71:359-70.
Helen, AB, Jos HB, Kenneth RB. Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of p-glycoprotein. Clin Cancer Res 2000;6:4416-21.
Sandra Peltier, Jean-Michel Oger, Fre´de´ ric Lagarce, William Couet, Jean-Pierre Benoıt. Enhanced oral paclitaxel bioavailability after administration of paclitaxel loaded lipid nanocapsules. Pharm Res 2006;23:1243-50.
Childs SL, LJ Chyall. Crystal engineering approach to forming cocrystals of amine hydrochlorides with organic acids’, molecular complexes of fluoxetine hydrochloride with benzoic, succinic, and fumaric acids. J Am Chem Soc 2004;126:13335-42.
Pei-Yin Hoa, Teng-Kuang Yeha, Hsien-Tsung Yaoa, Heng-Liang Lina, Hsin-YiWua, Yu-Kang Loa, et al. Enhanced oral bioavailability of paclitaxel by d-alpha-tocopheryl polyethylene glycol 400 succinate in mice. Int J Pharm 2008;359:174-81.
Muddukrishna BS, Bhat Krishnamurthy, Shenoy Gautham G. Preparation and solid state characterization of paclitaxel cocrystals. Res J Pharm Technol 2014;7:64-9.
Desiraju GR. Crystal engineering: the design of organic solids, Elsevier, Amsterdam; 1989.
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