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. Novel application of mixed hydrotropic solubilization technique in the formulation and evaluation of solid dispersion of flupirtine maleate, Journal of Drug Delivery and Therapeutics. 2018; 8(5):481-488 DOI: http://dx.

Snedds as Lipid-Based Nanocarrier Systems: Concepts and Formulation Insights

“…Nanocarriers provide several advantages, such as preventing active drugs from degrading, allowing for higher and more efficient concentrations in the target tissue, and reducing the severity of toxic side effects [16]. The lipid-based nanocarriers have greater importance due to their low toxicity [17], high drug-loading capacity [18], improved bioavailability [19], high biocompatibility [20], high protection from degradation in the gastrointestinal tract (GIT [21], controlled-release behavior [3], ease to scale-up and sterilize [6], easy to validate [2], and also useful for the administration of drugs through different routes [17]. Unique properties like, tailorable surface to apply any targeting strategy, and an improved bio distribution and pharmacokinetic profile makes lipid-based system as a unique approach.…”

“…The drug is enclosed in between the phosphor-lipid bilayer. Non-vesicular systems are colloidal preparations containing physiological lipids and surfactants in which the drug in encapsulated within the solid lipid matrix [18]. Table 1 illustrates the difference between the various types of lipid-based nanocarriers.…”

“…The conventional techniques are salt forms, solid dispersions [16], use of co-solvents [12], hydrotropy, micronization, change in dielectric constant of solvent, amorphous forms [7], chemical modification of drug, use of surfactants, inclusion complex [3], alteration of pH of solvent, use of hydrates or solvates [6], use of soluble prodrugs [8], application of ultrasonic waves [9], functional polymer technology, controlled precipitation technology [12], evaporative precipitation in aqueous solution [18], use of precipitation inhibitors, solvent deposition [4], precipitation [2], selective adsorption on insoluble carriers [9]. However, conventional approaches have many limitations like for example salt formation [12] of drugs is commonly used but always unattainable.…”

Enhanced Solubility of Meloxicam with Sodium Benzoate Hydrotrope: Ecofriendly Approach for Improved Topical Drug Delivery

“…Then prepared solid dispersion was stored in an appropriate air-tight container. [34][35][36][37][38][39][40] Similarly, a physical mixture of Meloxicam and sodium benzoate was also prepared in ratio of 1:4. Intense trituration of drug and hydrotrope was performed for 10 min in mortar and pestle.…”

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“…Many drugs that are poorly water-soluble have had their aqueous solubility improved by mixed hydrotropic solubilization. [4][5][6][7][8][9][10][11] Benefits of mixed hydrotropy…”