Login Register Cart 0
Generic placeholder image

Drug Delivery Letters

Editor-in-Chief

ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Nevirapine Pharmaceutical Cocrystal: Design, Development and Formulation

Author(s): Prabhakar Panzade*, Priyanka Somani and Pavan Rathi

Volume 9, Issue 3, 2019

Page: [240 - 247] Pages: 8

DOI: 10.2174/2210303109666190411125857

Price: $65

Abstract

Background and Objective: The top approach to deliver poorly soluble drugs is the use of a highly soluble form. The present study was conducted to enhance the solubility and dissolution of a poorly aqueous soluble drug nevirapine via a pharmaceutical cocrystal. Another objective of the study was to check the potential of the nevirapine cocrystal in the dosage form.

Methods: A neat and liquid assisted grinding method was employed to prepare nevirapine cocrystals in a 1:1 and 1:2 stoichiometric ratio of drug:coformer by screening various coformers. The prepared cocrystals were preliminary investigated for melting point and saturation solubility. The selected cocrystal was further confirmed by Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC), and Xray Powder Diffraction (XRPD). Further, the cocrystal was subjected to in vitro dissolution study and formulation development.

Results: The cocrystal of Nevirapine (NVP) with Para-Amino Benzoic Acid (PABA) coformer prepared by neat grinding in 1:2 ratio exhibited greater solubility. The shifts in IR absorption bands, alterations in DSC thermogram, and distinct XRPD pattern showed the formation of the NVP-PABA cocrystal. Dissolution of NVP-PABA cocrystal enhanced by 38% in 0.1N HCl. Immediate release tablets of NVP-PABA cocrystal exhibited better drug release and less disintegration time.

Conclusion: A remarkable increase in the solubility and dissolution of NVP was obtained through the cocrystal with PABA. The cocrystal also showed great potential in the dosage form which may provide future direction for other drugs.

Keywords: Nevirapine, cocrystal, solubility, dissolution, tablet, neat grinding.

« Previous Next »
Graphical Abstract

[1]
Kuminek, G.; Cao, F.; Da Rocha, A.B.; Cardoso, S.G.; Rodriguez-Hornedo, N. Cocrystals to facilitate delivery of poorly soluble compounds beyond-rule-of-5. Adv. Drug Deliv. Rev., 2016, 101, 143-166.
[2]
Bolla, G.; Nangia, A. Pharmaceutical cocrystals: Walking the talk. Chem. Commun., 2016, 52(54), 8342-8360.
[3]
Panzade, P.S.; Shendarkar, G.R. Pharmaceutical cocrystal: An antique and multifaceted approach. Curr. Drug Deliv., 2017, 14(8), 1097-1105.
[4]
Ullah, M.; Hussain, I.; Sun, C.C. The development of carbamazepine-succinic acid cocrystal tablet formulations with improved in vitro and in vivo performance. Drug Dev. Ind. Pharm., 2016, 42(6), 969-976.
[5]
Rodriguez-Aller, M.; Guillarme, D.; Veuthey, J.L.; Gurny, R. Strategies for formulating and delivering poorly water-soluble drugs. J. Drug Deliv. Sci. Technol, 2015, 30(b), 342-351.
[6]
Yamashita, H.; Sun, C.C. Improving dissolution rate of carbamazepine-glutaric acid cocrystal through solubilization by excess coformer. Pharm. Res., 2018, 35(1), 4.
[7]
Wang, F.Y.; Zhang, Q.; Zhang, Z.; Gong, X.; Wang, J.R.; Mei, X. Solid-state characterization and solubility enhancement of apremilast drug-drug cocrystals. CrystEngComm, 2018, 20(39), 5945-5948.
[8]
Di, L.; Fish, P.V.; Mano, T. Bridging solubility between drug discovery and development. Drug Discov. Today, 2012, 17(9-10), 486-495.
[9]
Lange, L.; Lehmkemper, K.; Sadowski, G. Predicting the aqueous solubility of pharmaceutical cocrystals as a function of pH and temperature. Cryst. Growth Des., 2016, 16(5), 2726-2240.
[10]
Miroshnyk, I.; Mirza, S.; Sandler, N. Pharmaceutical co-crystals-an opportunity for drug product enhancement. Expert Opin. Drug Deliv., 2009, 6(4), 333-341.
[11]
Maeno, Y.; Fukami, T.; Kawahata, M.; Yamaguchi, K.; Tagami, T.; Ozeki, T.; Suzuki, T.; Tomono, K. Novel pharmaceutical cocrystal consisting of paracetamol and trimethylglycine, a new promising cocrystal former. Int. J. Pharm., 2014, 473(1), 179-186.
[12]
Izutsu, K.I.; Koide, T.; Takata, N.; Ikeda, Y.; Ono, M.; Inoue, M.; Fukami, T.; Yonemochi, E. Characterization and quality control of pharmaceutical cocrystals. Chem. Pharm. Bull. , 2016, 64(10), 1421-1430.
[13]
Caira, M.R.; Bourne, S.A.; Samsodien, H.; Engel, E.; Liebenberg, W.; Stieger, N.; Aucamp, M. Co-crystals of the antiretroviral nevirapine: Crystal structures, thermal analysis and dissolution behaviour. CrystEngComm, 2012, 14(7), 2541-2551.
[14]
Das, S.K.; Roy, S.; Kalimuthu, Y.; Khanam, J.; Nanda, A. Solid dispersions: An approach to enhance the bioavailability of poorly water-soluble drugs. Int. J. Pharmacol. Pharm. Technol., 2012, 1(1), 37-46.
[15]
Shegokar, R.; Singh, K.K. Nevirapine nanosuspensions for HIV reservoir targeting. Die Pharmazie, 2011, 66(6), 408-415.
[16]
Raju, A.; Reddy, A.J.; Satheesh, J.; Jithan, A.V. Preparation and characterisation of nevirapine oral nanosuspensions. Indian J. Pharm. Sci., 2014, 76(1), 62.
[17]
Mulye, S.P.; Jamadar, S.A.; Karekar, P.S.; Pore, Y.V.; Dhawale, S.C. Improvement in physicochemical properties of ezetimibe using a crystal engineering technique. Powder Technol., 2012, 222, 131-138.
[18]
Shayanfar, A.; Jouyban, A. Physicochemical characterization of a new cocrystal of ketoconazole. Powder Technol., 2014, 262, 242-248.
[19]
El-Gizawy, S.A.; Osman, M.A.; Arafa, M.F.; El Maghraby, G.M. Aerosil as a novel co-crystal co-former for improving the dissolution rate of hydrochlorothiazide. Int. J. Pharm., 2015, 478(2), 773-778.
[20]
Panzade, P.; Shendarkar, G.; Shaikh, S.; Rathi, P.B. Pharmaceutical cocrystal of piroxicam: Design, formulation and evaluation. Adv. Pharm. Bull., 2017, 7(3), 399.
[21]
Gadade, D.D.; Kulkarni, D.A.; Rathi, P.B.; Pekamwar, S.S.; Joshi, S.S. Solubility enhancement of lornoxicam by crystal engineering. Indian J. Pharm. Sci., 2017, 79(2), 277-286.
[22]
Cheney, M.L.; Weyna, D.R.; Shan, N.; Hanna, M.; Wojtas, L.; Zaworotko, M.J. Coformer selection in pharmaceutical cocrystal development: A case study of a meloxicam aspirin cocrystal that exhibits enhanced solubility and pharmacokinetics. J. Pharm. Res., 2011, 100(6), 2172-2181.
[23]
Ganesh, M.; Jeon, U.J.; Ubaidulla, U.; Hemalatha, P.; Saravanakumar, A.; Peng, M.M. Chitosan cocrystals embedded alginate beads for enhancing the solubility and bioavailability of aceclofenac. Int. J. Biol. Macromol., 2015, 74, 310-317.
[24]
Chen, Y.; Li, L.; Yao, J.; Ma, Y.Y.; Chen, J.M.; Lu, T.B. Improving the solubility and bioavailability of apixaban via apixaban-oxalic acid cocrystal. Cryst. Growth Des., 2016, 16(5), 2923-2930.

Rights & Permissions Print Cite
Article Metrics
26
6
1
1
© 2024 Bentham Science Publishers | Privacy Policy