Novel Pharmaceutical Applications of Hydrotropy, Mixed Hydrotropy & Mixed Solvency

Various organic solvents like ethanol, methanol, dimethylformamide, acetonitrile ethylacetate, toluene, chloroform, benzene, dichloromethane, carbon tetrachloride, acetone, hexane etc. have been employed for spectrophotometric estimations of poorly water-soluble drugs. Similarly, various organic solvents like ethanol, methanol, dimethylformamide etc have been employed for titrimetric estimations of poorly water-soluble drugs. Drawbacks of organic solvents include higher cost, toxicity and pollution. Organic solvents have innumerous adverse effects caused by single exposure like dermatitis, headache, drowsiness, nausea, eye irritation and long term exposure causes serious effects such as neurological disorders, chronic renal failure, liver damage, necrosis, mutagenesis disorder. They should be replaced by other eco-friendly alternative sources.

Pharmacopoeial (Indian/British) titrimetric analytical methods for bulk drugs of ibuprofen, frusemide, aceclofenac, salicylic acid, ketoprofen, chlorpropamide, phenyl butazone etc involve the use of organic solvents (ethanol, methanol, dimethyl formamide etc). Hydrotropic aqueous solutions of sodium benzoate, sodium acetate, sodium citrate, sodium salicylate, urea, dimethyl urea, niacinamide etc (as well as aqueous solutions of mixed blends of hydrotropic agents) could be employed for such titrimetric analyses precluding the use of organic solvents.

Pharmacopoeial (Indian/British) spectrophotometric analytical methods for tablets of tinidazole, atenolol and diclofenac sodium involve the use of a toxic organic solvent, methanol. However, hydrotropic aqueous solutions of sodium benzoate and urea could be used for spectrophotometric analysis of tablets of these poorly water soluble drugs precluding the use of methanol. Tablets/Capsules of a large number of poorly water soluble drugs such as naproxen, famotidine, frusemide, metronidazole, nalidixic acid, hydrochlorothiazide, gatifloxacin, aceclofenac, paracetamol, ofloxacin, norfloxacin, atenolol, diclofenac sodium, piroxicam, tinidazole, ketoprofen etc have been estimated spectrophotometrically using hydrotropic aqueous solutions of sodium benzoate, sodium acetate, sodium citrate, urea, dimethyl urea, niacinamide etc (as well as using aqueous solutions of mixed blends of hydrotropic agents) precluding the use of organic solvents.

Maheshwari has proposed the mixed-solvency concept. The mixed solvency concept states that all substances whether liquid, gas or solid possess solubilizing power. Solids play very important role in improving the solubilities of drugs in different solvents. A weaker solvent may act as strong solvent for a particular solute in the presence of other solid (in solution form). For example the solubility of frusemide in ethanol is improved in presence of niacinamide (three times enhancement in solubility in presence of 15% w/v niacinamide in ethanol). In order to improve aqueous solubility of a poorly water-soluble drug, the concentrated aqueous solution containing various dissolved excipients (liquids and solids both) can give successful results in solubility enhancrment. In one of the study by Maheshwari1, it was found that additive and synergistic solvent action on the solubility of salicylic acid could be obtained by using aqueous solutions containing different excipients (liquids and solids both). Mixed-solvency concept shall be helpful to formulate various dosage forms of insoluble drugs utilizing safe concentrations of excipients for solubilization.

Similarly TLC of several poorly water soluble drugs could be performed using hydrotropic solutions precluding the use of organic solvents.

Hydrotropy, mixed hydrotropy and mixed-solvency can give alternate methods in following fields precluding the use of organic solvents-

  1. Herbal extractions
  2. Herbal formulations
  3. Cosmetic preparations
  4. Chemical synthesis
  5. Purification processes
  6. HPLC analysis
  7. Dyeing industry
  8. Chemical technologies involving solutions of insoluble substances
  9. Ink industry
  10. Paint industry etc
  11. Pharmaceutical dosage forms including NDDS (microspheres, SEDDS, multiple emulsions, transdermal gels, nasal gels etc)

REFERENCES

A—MIXED SOLVENCY REFERENCES

  1. Maheshwari RK. “Mixed-solvency approach”- Boon for solubilization of poorly water-soluble drugs. Asian J Pharm 2010;4(1):60-3.
  2. Maheshwari RK. Solubilization of ibuprofen by mixed solvency approach. Indian Pharm 2009;8(87):81-4.
  3. Maheshwari RK. “Mixed- solvency” – A novel concept for solubilization of poorly water-soluble drugs. Delving J. Tech Eng Sci 2009;1(1):39-43.
  4. Maheshwari RK, Shilpkar R. Formulation development and evaluation of injection of poorly soluble drug using mixed solvency concept. Int J Pharm Biosci 2012;3(1):179-89.
  5. Maheshwari RK, Upadhyay N, Jain J, Patani M, Mathuria KC. New spectrophotometric estimation of naproxen tablet formulation employing mixed solvency concept (at 331 nm). Int J Pharm Technol 2011;3(4):3618-23.
  6. Soni LK, Solanki SS, Maheshwari RK. Solubilization of poorly water soluble drug using mixed solvency approach for aqueous injection. Br J Pharm Res 2014;4(5):549-68.
  7. Maheshwari Y, Mishra DK, Mahajan SC, Maheshwari P, Maheshwari RK, Jain J. Novel pharmaceutical application of mixed solvency in the formulation development of syrups (liquid oral solutions) of poorly water-soluble drugs. International Journal of Pharmacy 2013; 3(4):753-58.
  8. Maheshwari RK, Gupta S, Gharia A, Garg SK, Shilpkar R. Simple eco-friendly spectrophotometric estimation of tinidazole tablets by application of mixed-solvency technique. Bull Pharm Res 2011;1(1):22-5.
  9. Maheshwari RK, Rajagopalan R. Formulation and evaluation of paracetamol syrup made by mixed-solvency concept. Der Pharm Lett 2012;4(1):170-4.
  10. Maheshwari RK, Rajagopalan R. Formulation and evaluation of tinidazole syrup made by mixed-solvency concept. Der Pharm Lett 2011;3(6):266-71.
  11. Bhawsar N, Maheshwari RK, Ansari A, Saktawat Y. New spectrophotometric estimation of gatifloxacin in the tablets using mixed solvency approach. Int J Pharm Sci 2011;2(2):270-4.
  12. Maheshwari RK, Karawande VU, Application of novel concept of mixed solvency in the design and development of floating microspheres of furosemide. Int J Pharm Pharm Sci 2013,15:167-95.
  13. Maheshwari RK, Upadhyay N, Jain J, Patani M, Pandey R. New spectrophotometric analysis of gatifloxacin tablets utilizing mixed solvency concept (at 288 nm). Der Pharm Lett 2012;4(1):1-4.
  14. Agrawal A, Maheshwari RK. Formulation development and evaluation of in situ nasal gel of poorly water soluble drug using mixed solvency concept. Asian J Pharm 2011;5(3);131-40.
  15. Prashant B, Rawat S, Mahajan YY, Galgatte UC, Maheshwari RK. Formulation development and evaluation of aqueous injection of poorly soluble drug made by novel application of mixed solvency concept. Int J Drug Delivery 2013;2:152-66.
  16. Chandna C, Maheshwari RK. Mixed solvency concept in reducing surfactant concentration of self emulsifying drug delivery systems of candesartan cilexetil using D-optimal mixture design. Asian J Pharm 2013;7(2):83-91.
  17. Maheshwari RK. Potentiation of solvent character by mixed solvency concept: A novel concept of solubilization. J Pharm Res 2010;3(2):411-3.
  18. Maheshwari RK. “Solid as solvent”- Novel spectophotometric analysis of satranidazole tablets using phenol as solvent”. Indian Pharm 2014;12:37-40.
  19. Maheshwari RK. “Solid as solvent”- Novel spectophotometric analysis of norfloxacin tablets using phenol as solvent”. International Journal of Current Pharmaceutical Research 2014;6:76-8.
  20. Maheshwari RK, Shilpkar R. Formulation development and evaluation of injection of poorly soluble drug using mixed solvency concept. Int J Pharm Biosci 2012;3(1):179-89.
  21. Maheshwari RK. “Solid as solvent”-Novel spectrophotometric analysis of frusemide tablets using phenol as solvent. Bulletin of Pharmaceutical Research 2014;4(2):104-107.
  22. Maheshwari RK. “Solid as solvent”-Novel spectrophotometric analysis of tinidazole tablets using melted phenol as solvent. Asian Journal of Pharmaceutical Research 2015;5(1):21-24.
  23. Maheshwari RK, Putliwala M, Padiyar A. Novel approach for spectrophotometric estimation of naproxen in tablet dosage form using solids (eutectic liquid of phenol and niacinamide) as solubilizing agent (mixed solvency concept). Asian Journal of Pharmaceutical Research, 2015;5(1):25-28.

PLEASE SEE OTHER REFERENCES ON MIXED SOLVENCY CONCEPT IN MIXED SOLVENCY SECTION

 

B —- REFERENCES OF HYDROTROPY AND MIXED HYDROTROPY

—–Please refer hydrotropy and mixed hydrotropy sections

 

 

 

 

 

 

 

 

 

 

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