NOVEL APPLICATION OF MIXED HYDROTROPIC SOLUBILIZATION TECHNIQUE IN THE FORMULATION AND EVALUATION OF SOLID DISPERSION OF FLUPIRTINE MALEATE
Abstract
Flupirtine is an amino pyridine derivative that functions as a centrally acting non-opioid, non-steroidal analgesic. It is a selective neuronal potassium channel opener that also has NMDA receptor antagonist properties. Its muscle relaxant properties make it popular for back pain and other orthopedics uses. In the present investigation, recently developed mixed hydrotropic solid dispersion technology precludes the use of organic solvent and also decreases the individual concentration of hydrotropic agents, simultaneously decreasing their toxic potential. Mixed-hydrotropic solubilisation technique is the experience to increase the solubility of poorly water soluble drugs in the aqueous solution containing blends of hydrotropic agents, which may give synergistic enhancement effect on solubility of poorly water-soluble drugs and to reduce concentrations of each individual hydrotropic agent to minimize their toxic effects due to high concentration of hydrotropic agents. The Flupirtine loaded solid dispersion was prepared by a solvent evaporation technique using sodium benzoate and a niacinamide hydrotropic mixture. The prepared solid dispersions were valuated regarding their solubility, mean particle size, in-vitro drug release. The prepared solid dispersions were found very stable (chemically). The superior dissolution rate due to its reduced particle size may have contributed to the increased oral bioavailability. This study demonstrated that mixed-solvency may be an alternative approach for poorly soluble drugs to improve their solubility and oral bioavailability.
Keywords: Flupirtine, Solid dispersion, Mixed-hydrotropic solubilisation, Solvent evaporation technique, Sodium benzoate, Niacinamide
DOI
https://doi.org/10.22270/jddt.v8i5.1911References
Bothiraja C, Pawar AP, Mali AJ, Shaikh KS. Improved pharmaceutical properties of surface modified bioactive plumbagin crystals, International Journal of Surface Science and Engineering, 2013; 7(2):181-195.
Kamble RN, Mehta PP, Kumar A. Efavirenz self-nano-emulsifying drug delivery system: in vitro and in vivo evaluation, AAPS Pharm Sci Tech, 2016; 17(5):1240-7.
Neuberg C. Hydrotropic phenomena, Biochemische Zeitschrift, 1916; 76:107.
Saleh AM, El-Khordagui LK. Hydrotropic agents: a new definition, International Journal of Pharmaceutics, 1985; 24(2-3):231–238.
Lee S, Huh K, Lee J, Cho Y, Galinsky R, Park K. Hydrotropic polymeric micelles for enhanced paclitaxel solubility: in vitro and in vivo characterization, Biomacromolecules, 2007; 8:202-208.
Hodgdon TK, Kaler EW. Hydrotropic solutions, Current Opinion in Colloid and Interface Science, 2007; 12(3):121-128.
Abdelbary GA, Amin MM, Abdelmotele M. Novel mixed hydrotropic solubilization of Zaleplon: Formulation of oral tablets and in-vivo neuropharmacological characterization by monitoring plasma GABA level, Journal of Drug Delivery Science and Technology, 2016; 33:98-113.
Kim JY, Kim S, Papp M, Park K, Pinal R. Hydrotropic solubi-lization of poorly water-soluble drugs, Journal of Pharmaceutical Sciences, 2010; 99(9):3953-3965.
Dhapte V, Mehta P. Advances in hydrotropic solutions: an updated review, St. Petersburg Polytechnical University Journal: Physics and Mathematics, 2015; 1(4):424-435.
Friberg SE, Brancewicz C, Morrison DS. O/W microemulsions and hydrotropes: the coupling action of a hydrotrope, Langmuir, 1994; 10(9):2945–2949.
Szabo K, Wang P, Peles-Lemli B, Fang Y, Kollar L, Kunsagi-Mate S., Structure of aggregate of hydrotropic p-toluene sulfonate and hydroxyacetophenone isomers, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2013; 422: 143–147.
Vasanthavada M, Tong WQ, Serajuddin Abu TM. Water-insoluble drug formulation. London: CRS press; 2008; p. 500-20.
Rao MG, Suneetha R, Sudhakara P, Reddy S, Ravi TK. Preparation and evaluation of solid dispersion of naproxen, Indian Journal of Pharmaceutical Sciences, 2005; 64:26-9.
Saha RN, Sajeev C, Priya KP, Sreekhar C, Shashikant G. Solubility enhancement of nimesulide and ibuprofen by solid dispersion technique, Indian Journal of Pharmaceutical Sciences, 2006; 67:529-34.
Klinger F, Geier P, Dorostkar MM, et al. Concomitant facilitation of GABA(A) receptors and K(V) 7 channels by the non-opioid analgesic flupirtine, British Journal of Pharmacology, 2012; 166(5):1631-1642.
Kornhuber J, Bleich S, Wiltfang J, Maler M, Parsons CG. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels, Journal of Neural Transmission, 1999; 106(9-10):857–867.
Raffa RB, Pergolizzi JV Jr. The evolving understanding of the analgesic mechanism of action of flupirtine, Journal of Clinical Pharmacy and Therapeutics, 2012; 37(1):4–6.
Friedel HA, Fitton A. Flupirtine, A review of its pharmacological properties and therapeutic efficacy in pain states. Drugs. 1993; 45(4):548–569.
Harish S, Bhuvana K, Bengalorkar GM, Kumar TN. Flupirtine: clinical pharmacology, Journal of Anaesthesiology Clinical Pharmacology, 2012; 28(2):172–177.
Devulder J. Flupirtine in pain management: pharmacological properties and clinical use. CNS Drugs, 2010; 24(10):867-881.
Klawe C, Maschke M. Flupirtine: pharmacology and clinical applications of a nonopioid analgesic and potentially neuro protective compound, Expert Opinion Pharmacotherapy, 2009; 10(9):1495-1500.
Uberall MA, Mueller-Schwefe GH, Terhaag B. Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo and active-controlled parallel-group phase IV study, Current Medical Research Opinion. 2012; 28(10):1617–1634.
Otto M, Cepek L, Ratzka P, et al. Efficacy of flupirtine on cognitive function in patients with CJD: a double-blind study, Neurology, 2004; 62(5):714-718.
Sattler MB, Williams SK, Neusch C, et al. Flupirtine as neuroprotec¬tive add-on therapy in autoimmune optic neuritis, American Journal of Pathology,. 2008; 173(5):1496–1507.
Schroder HC, Muller WE. Neuroprotective effect of flupirtine in Prion disease, Drugs Today (Barc), 2002; 38(1):49-58.
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