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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Non-Invasive Extraction of Gabapentin for Therapeutic Drug Monitoring by Reverse Iontophoresis: Effect of pH, Ionic Strength, and Polyethylene Glycol 400 in the Receiving Medium

Author(s): Tapan Kumar Giri, Subhasis Chakrabarty and Bijaya Ghosh*

Volume 15, Issue 6, 2019

Page: [632 - 639] Pages: 8

DOI: 10.2174/1573412914666180910115059

Price: $65

Abstract

Background: Monitoring of plasma concentrations is a necessity for narrow therapeutic index potent drugs. Development of non-invasive methods can save the patients from the trauma of needles and hence is considered as a research priority.

Introduction: Gabapentin, an anti-epileptic drug requires therapeutic monitoring because of its narrow therapeutic index. The objective of the study was to develop a suitable method for the non-invasive extraction of gabapentin for the same.

Methods: Transdermal reverse iontophoresis was performed using pig ear skin as a barrier membrane. Three compartment iontophoretic cells were used for the extraction study. Extractions were carried out under low intensity electric field (current intensity- 0.5 mA/cm2, electrical field approximately 5 V). The donor compartment was charged with aqueous gabapentin (10 µg/ml in phosphate buffer of pH 7.4). For studying the effect of receiving vehicle (pH, ionic strength, and enhancer) on the extraction efficiency of gabapentin, the two receiver chambers were charged with media having varying concentration of these factors. Drug content was determined by HPLC.

Results: Compared to other pHs, cumulative extraction of gabapentin at pH 5 was significantly higher at both anode and cathode (p<0.001). At low ionic strength, extraction of gabapentin increased linearly with the increase in concentration of ions up to a certain value but at very high ionic strength the pattern reversed. Similar results were obtained with enhancer (polyethylene glycol 400). Extraction increased with increase in polyethylene glycol 400 up to 3% and then decreased.

Conclusion: Extraction flux can be optimized by manipulation of the receiver media.

Keywords: Reverse iontophoresis, non invasive extraction, gabapentin, permeation enhancer, pig ear skin, pH.

Graphical Abstract
[1]
El-Shaboury, S.R.; El-Gizawy, S.M.; Atia, N.N.; Abo-Zeid, M.N. Validated spectrodensitometric method for simultaneous estimation of sofosbuvir, ribavirin and saxagliptin in their pure and pharmaceutical dosage forms. Curr. Pharm. Anal., 2018, 14, 212-218.
[2]
Bajerski, L.; Maciel, T.R.; Haas, S.E. Simultaneous determination of curcumin and quinine co-encapsulated in nanoemulsion by stability-indicating lc method. Curr. Pharm. Anal., 2018, 14, 255-261.
[3]
Ahmed, S.; Khan, A.; Sheraz, M.A.; Bano, R.; Ahmad, I. Development and validation of a stability-indicating hplc method for the assay of carvedilol in pure and tablet dosage forms. Curr. Pharm. Anal., 2018, 14, 139-152.
[4]
Joshi, S.A.; Jalalpure, S.S.; Kempwade, A.A.; Peram, M.R. Development and validation of HPLC method to determine colchicine in pharmaceutical formulations and its application for analysis of solid lipid nanoparticles. Curr. Pharm. Anal., 2018, 14, 76-83.
[5]
Wang, W.; Vellaisamy, K.; Li, G.; Wu, C.; Ko, C.N.; Leung, C.H.; Ma, D.L. Development of a long-lived luminescence probe for visualizing β-Galactosidase in ovarian carcinoma cells. Anal. Chem., 2017, 89, 11679-11684.
[6]
Lin, S.; Lu, L.; Kang, T.S.; Mergny, J.L.; Leung, C.H.; Ma, D.L. Interaction of an Iridium(III) Complex with G-Quadruplex DNA and its application in luminescent switch-on detection of siglec-5. Anal. Chem., 2016, 88, 10290-10295.
[7]
Liu, C.; Yang, C.; Lu, L.; Wang, W.; Tan, W.; Leung, C.H.; Ma, D.L. Luminescent iridium(III) complexes as COX-2-specific imaging agents in cancer cells. Chem. Commun., 2017, 53, 2822-2825.
[8]
Wang, M.; Mao, Z.; Kang, T.S.; Wong, C.Y.; Mergny, J.L.; Leung, C.H.; Ma, D.L. Conjugating a groove-binding motif to an Ir(III) complex for the enhancement of G-quadruplex probe behavior. Chem. Sci., 2016, 7, 2516-2523.
[9]
Hori, Y.; Otomura, N.; Nishida, A.; Nishiura, M.; Umeno, M.; Suetake, I.; Kikuchi, K. Synthetic-molecule/protein hybrid probe with fluorogenic switch for live-cell imaging of dna methylation. J. Am. Chem. Soc., 2018, 140, 1686-1690.
[10]
Rodriguez, J.; Castaneda, G.; Lizcano, I.; Villa, J.C. A rapid, direct and validated hplc- fluorescence method for the quantification of abiraterone and abiraterone acetate in urine and serum samples from patients with castration- resistant prostate cancer. Curr. Pharm. Anal., 2018, 14, 233-238.
[11]
Hu, Y.; Feng, J.; Liang, G. Vinoprabath.; Fu, L.; Pan, J.; Zhang, X.; Xiang, Z. A rapid and simple UPLC method for the quantitative determination of compound X22 in rat plasma and its application to a pharmacokinetic study. Curr. Pharm. Anal., 2018, 14, 116-120.
[12]
Shah, A.; Kothari, C.; Patel, N. Concurrent estimation of gabapentin and nortriptyline hydrochloride in their combined dosage form using OPA-β-Mercaptoethanol derivatization by spectrophotometric and spectrofluorimetric methods. Curr. Pharm. Anal., 2017, 13, 241-249.
[13]
Jalalizadeh, H.; Souri, E.; Tehrani, M.B.; Jahangiri, A. Validated HPLC method for the determination of gabapentin in human plasma using pre-column derivatization with 1-fluoro-2,4-dinitrobenzene and its application to a pharmacokinetic study. J. Chromatogr. B , 2007, 854, 43-47.
[14]
Gupta, A.; Ciavarella, A.B.; Sayeed, V.A.; Khan, M.A.; Faustin, P.J. Development and application of a validated HPLC method for the analysis of dissolution samples of gabapentin drug products. J. Pharm. Biomed. Anal., 2008, 46, 181-186.
[15]
Bartoszyk, G.D.; Meyerson, N.; Reimann, W.; Satzinger, G.; von-Hodenberg, A. “Gabapentin,” in New Anticonvulsant Drugs. B S Meldrum and B. J. Porter, Eds. 1986 pp. 147-163, John Libbey London, UK
[16]
Tallian, K.B.; Nahata, M.C.; Lo, W.; Tsao, C.Y. Pharmacokinetics of gabapentin in paediatric patients with uncontrolled seizures. J. Clin. Pharm. Ther., 2004, 29, 511-515.
[17]
Ouellet, D.; Bockbrader, H.N.; Wesche, D.L.; Shapiro, D.Y.; Garofalo, E. Population pharmacokinetics of gabapentin in infants and children. Epilepsy Res., 2001, 47, 229-241.
[18]
Taylor, C.P.; Angelotti, T.; Fauman, E. Pharmacology and mechanism of action of pregabalin: The calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res., 2007, 73, 137-150.
[19]
Ramsey, R.E. Clinical efficacy and safety of gabapentin. Neurology, 1994, 44(suppl 5), 523-530.
[20]
Sivenius, J.; Kalvianinen, R.; Ylinin, A.; Riekkinin, P. Double blind study of gabapentin in the treatment of partial seizures. Epilepsia, 1991, 32, 539-542.
[21]
Johannessen, S.I.; Tomson, T. Pharmacokinetics variability of newer antiepileptic drugs: When is monitoring needed? Clin. Pharmacokinet., 2006, 45, 1061-1075.
[22]
Krasowski, M.D. Therapeutic drug monitoring of the newer antiepilepsy medications. Pharmaceuticals, 2010, 3, 1909-1935.
[23]
Dahl, J.B.; Mathiesen, O.; Møiniche, S. Protective premedication’: An option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of post-operative pain. Acta Anaesthesiol. Scand., 2004, 48, 1130-1136.
[24]
Markman, J.D.; Dworkin, R.H. Ion channel targets and treatment efficacy in neuropathic pain. J. Pain, 2006, 7(1 Suppl 1), S38-S47.
[25]
Nair, A.B.; Kumria, R.; Al-Dhubiab, B.E. Noninvasive sampling of gabapentin by reverse iontophoresis. Pharm. Res., 2015, 32, 1417-1424.
[26]
Berry, D.J.; Beran, R.G.; Plunkeft, M.J.; Clarke, L.A.; Hung, W.T. The absorption of gabapentin following high dose escalation. Seizure, 2003, 12, 28-36.
[27]
Giri, T.K.; Chakrabarty, S.; Ghosh, B. Transdermal reverse iontophoresis: A novel technique for therapeutic drug monitoring. J. Controlled. Release, 2017, 246, 30-38.
[28]
Leboulanger, B.; Guy, R.H.; Delgado-Charro, M.B. Non invasive monitoring of phenytoin by reverse iontophoresis. Eur. J. Pharm. Sci., 2004, 22, 427-433.
[29]
Tamada, J.A.; Garg, S.; Jovanovic, L.; Pitzer, K.R.; Fermi, S.; Potts, R.O. Noninvasive glucose monitoring: comprehensive clinical results. J Am. Med. Assoc, 1999, 282, 1839-1844.
[30]
Pitzer, K.R.; Desai, S.; Dunn, T.; Edelman, S.; Jayalakshmi, Y.; Kennedy, J.; Tamada, J.A.; Potts, R.O. Detection of hypo- glycemia with the GlucoWatch biographer. Diabetes Care, 2001, 24, 881-885.
[31]
Degim, I.T.; Ilbasmis, S.; Dundaroz, R.; Oguz, Y. Reverse iontophoresis: A non-invasive technique for measuring blood urea level. Pediatr. Nephrol., 2003, 18, 1032-1037.
[32]
Merino, V.; Lopez, A.; Hochstrasser, D.; Guy, R.H. Noninvasive sampling of phenylalanine by reverse iontophoresis. J. Control. Release, 1999, 61, 65-69.
[33]
Mize, N.K.; Buttery, M.; Daddona, P.; Morales, C.; Cormier, M. Reverse iontophoresis: monitoring prostaglandin E2 associated with cutaneous inflammation in vivo. Exp. Dermatol., 1997, 6, 298-302.
[34]
Nixon, S.; Sieg, A.; Delgado-Charro, M.B.; Guy, R.H. Reverse iontophoresis of Llactate: In vitro and in vivo studies. J. Pharm. Sci., 2007, 96, 3457-3465.
[35]
Delgado-Charro, M.B.; Guy, R.H. Transdermal reverse iontophoresis of valproate: a non-invasive method for therapeutic drug monitoring. Pharm. Res., 2003, 20, 1508-1513.
[36]
Leboulanger, B.; Guy, R.H.; Delgado-Charro, M.B. Non-invasive lithium monitoring by reverse iontophoresis. an in vivo study. Clin. Chem., 2004, 50, 2091-2100.
[37]
Santi, P.; Guy, R.H. Reverse iontophoresis - Parameters determining electroosmotic flow: I. pH and ionic strength. J. Controlled. Release, 1996, 38, 159-165.
[38]
Fluhr, J.W.; Elias, P.M. Stratum corneum pH: Formation and function of the acid mantle. Exog. Dermatol., 2002, 1, 163-175.
[39]
Martin, A. Physical Pharmacy, 4th ed; Williams and Wilkins: Baltimore, USA, 1993, pp. 169-190.
[40]
Sekkat, N.; Naik, A.; Kalia, Y.N.; Glikfeld, P.; Guy, R.H. Reverse iontophoretic monitoring in premature neonates: feasibility and potential. J. Controlled. Release, 2002, 81, 83-89.
[41]
Nojavan, S.; Pourahadi, A.; Davarani, S.S.H.; Morteza-Najarian, A.; Abbassi, M.B. Electromembrane extraction of zwitterionic compounds as acid or base: Comparison of extraction behavior at acidic and basic pHs. Analytica. Chimica. Acta, 2012, 745, 45-52.
[42]
Smith, K.A.; Hao, J.; Li, S.K. Effects of ionic strength on passive and iontophoretic transport of cationic permeant across human nail. Pharm. Res., 2009, 26, 1446-1455.
[43]
Ho, H.; Huang, F.; Soroloski, T.D.; Sheu, M. The influence of cosolvents on the in vitro percutaneous penetration of diclofenac sodium from a gel system. J. Pharm. Pharmacol., 1994, 46, 636-642.

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