Development and Biopharmaceutical Characterization of BCS Class II Drug – Naproxen by Two Way Complexation Solid Dispersion Technique

  • Milind Dharmraj Kamble Y B Chavan College of Pharmacy Aurangabad
  • Zahid Zaheer Y B Chavan College of Pharmacy Aurangabad
  • Santosh Mokale Y B Chavan College of Pharmacy Aurangabad
  • Rana Zainuddin Y B Chavan College of Pharmacy Aurangabad
Keywords: Formulation optimization, ternary solid dispersions, pharmacokinetic study

Abstract

The objective of this study was to increase the solubility and bioavailability of Naproxen (NP) by fabricating ternary solid dispersion (tSDs) with water soluble polymer PEG 6000 and crospovidone. tSDs were prepared and optimized by 32 full factorial design with PEG 6000 level (X1) and CP level (X2) as independent variables and percent drug release (D80, (Y)) as dependent variable. The optimized tSDs were evaluated for their physicochemical properties which confirmed the formation of tSDs (DSC), SEM suggested smooth surface and compact structures. PXRD revels that drug was still present in crystalline form and was not molecularly dispersed in the complex especially in non-homogeneous part of the tSDs. The optimized tSDs revels that Dissolution rate (Y) was significantly affected by independent variable PEG 6000 (X1) while CP (X2) was insignificant. The transparent characteristics of tSDs was observed as a result of lowered Tg temperature gives higher dissolution rate up to 97.70 % for optimized formulation (F9). The pharmacokinetic study in Han Wistar rats showed that the tSDs had the greatest effect on oral bioavailability of NP in vivo test showed that NP (tSDs) presented significantly larger AUC0-t, which was 1.09 folds more than that of marketed formulation. Cmax of NP (tSDs) also increased from 120 µg/ml to 146 µg/ml compared to that of marketed formulations and generated shortened Tmax of (1.0 ± 0.416) h, compared to marketed dosage form (2.0 ± 0.456) h.

References

D.M. Brahmankar, Sunil B. Jaiswal, Biopharmaceutics and pharmacokinetics A treatise, First edition, Vallabh Prakashan, New delhi, 19, 1995.

Giovanna Corti, Francesca Maestrelli and et al., Dissolution and permeation properties of Naproxen from solid-state systems with chitosan. Drug delivery, 15; 2008: 303-312

Eun-Jung Kim a, Myung-Kwan Chun and et al., Preparation of a solid dispersion of felodipine using a solvent wetting method. Euro. J. of Pharm and Biopharm, 64, 2006: 200–205

Sandrien Janssens, Jan Van Humbeeck, Guy Van den Mooter. Evaluation of the formulation of solid dispersions by co-spray drying itraconazole with Inutec SP1, a polymeric surfactant, in combination with PVPVA 64. Euro. J of Pharm and Biopharm, 70, 2008: 500–505.

Margarita V, Carmen C, et al., Ternary naproxen: β-cyclodextrin: polyethylene glycol complex formation. Int. J. of Pharmaceutics. 265, 2003: 141-149.

Kohsaku Kawakami, Modification of physicochemical characteristics of active pharmaceutical ingredients and application of super saturatable dosage forms for improving bioavailability of poorly absorbed drugs. Advanced Drug Delivery Reviews, 64, 2012: 480–495.

Ilse Weutsa, Dieter Kempena, Geert Verreck, et al., Study of the physicochemical properties and stability of solid dispersions of loperamide and PEG6000 prepared by spray drying. Euro. J. of Pharm and Biopharm, 59, 2005: 119–126

Aso Y, Yoshioka S, Kojima S. Molecular mobility-based estimation of the crystallization rates of amorphous nifedipine and phenobarbital in poly (vinylpyrrolidone) solid dispersions. J Pharm Sci. 93, 2004: 384–391.

Ye Sun, Lei Zhu, Tian Wu, et al., Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives. The AAPS Journal, 14 (3): 2012.

Namdeo R Jadhav, Vinod L Gaikwad, Karthik J Nair, and et al., Glass transition temperature: Basics and application in pharmaceutical sector. Asian Journal of Pharmaceutics. 2009.

Eugene S. Barabas and Christianah M. Adeyeye, Crospovidone. Analytical Profiles of Drug Substances and Excipients. 1996.

Khosro Adibkia, Mohammad Barzegar-Jalali, Hosein Maheri-Esfanjani, and et al., Physicochemical characterization of naproxen solid dispersions prepared via spray drying technology. Powder Technology. 246, 2013: 448–455.

Camelia Nicolescu, Corina Arama, Angela Nedelcu, et al., Phase solubility studies of the Inclusion complexes of Repaglinide with β-cyclodextrin and β-cyclodextrin derivatives. Farmacia, 58: (5) 2010; 620-628.

Sharma, C.P. Jain. Preparation and characterization of solid dispersions of carvedilol with PVP K30. Res Pharm Sci. 5(1) 2010: 49–56.

M. Barzegar-Jalali, M. Alaei-Beirami, Y. Javadzadeh, G. Mohammadi, A. Hamidi, S. Andalib, K. Adibka., Comparison of physicochemical characteristics and drug release of diclofenac sodium-eudragit RS 100 nanoparticles and solid dispersions. Powder Technol, 219 (2012) 211-216.

N. Tiong, A.A. Elkordy, Effects of liquisolid formulations on dissolution of naproxen, Eur. J. Pharm. Biopharm. 73 (3) (2009) 373-384.

T. Vasconcelos, B Sarmento, P. Costa, Solid dispersions as strategy to improve oral bioavailability of poor water-soluble drugs, Drug Discovery Today 12 (23/24) (2007) 1068-1075.

Paudel, Z.A. Worku, J. Meeus, S. Guns, G. Van den Mooter, Manufacturing of solid dispersions of poorly water-soluble drugs by spray drying: Formulation and process considerations. Int. J. Pharm.30; 453(1): 2013. 253-84.

G. Mohammadi, M. Barzegar-Jalali, H. valizadeh, H. Nazemiyeh, M. R. Siahi-Shadbad Alaei-Beirami, K. Adibka, M. Zare, Reciprocal powered time model for release kinetic analysis of ibuprofen solid dispersions in oleaster powder, microcrystalline cellulose and crospovidone. J. Pharm. Pharm. Sci. 13 (2) (2010) 152-161.

Published
2019-04-01
How to Cite
Kamble, M., Zaheer, Z., Mokale, S., & Zainuddin, R. (2019). Development and Biopharmaceutical Characterization of BCS Class II Drug – Naproxen by Two Way Complexation Solid Dispersion Technique. International Journal of Bio-Pharma Research, 8(4), 2523-2530. https://doi.org/10.21746/ijbpr.2019.8.4.1
Section
Research Article