Solubility enhancement of nimodipine using mixed hydrotropic solid dispersion technique

  • Naz Jamal Ibrahim Department of of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
  • Shahla Sadeq Smail Department of of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
  • Nozad Rashid Hussein Department of of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
  • Tara Abdulrahman Abdullah Department of of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Keywords: Hydrotropes, Nimodipine, Solubility enhancement, Solid dispersion


Background and objective: Low aqueous solubility of active pharmaceutical ingredients has an effect on both formulation development and bioavailability. Nimodipine is an antihypertensive agent with low oral bioavailability, which might be attributed to the extremely poor water solubility. This study aimed to increase the solubility of nimodipine in water using hydrotropes and solid dispersion technology to increase dissolution rate compared to the marketed drug product.

Methods: Solubility of nimodipine was determined separately in sodium acetate, sodium citrate, sodium benzoate, and niacinamide solutions at a concentration of 10, 20, 30, and 40% w/v using distilled water as a solvent. The highest solubility was obtained in 40% sodium benzoate solution. Mixed concentrations of hydrotropic agents were used in ratio 1:3 (niacinamide: sodium benzoate). Fourier-transform infrared spectroscopy was used to exclude any drug-hydrotropes interaction. The dissolution rate of nimodipine from solid dispersion and physical mixture were studied using USP type II dissolution test apparatus in acetate buffer (pH 4.5) as a dissolution media.

Results: Hydrotropic solid dispersion of nimodipine with a blend (30% sodium benzoate and 10% niacinamide) increased the dissolution rate of the drug by 1.5 folds compared to the marketed conventional nimodipine tablet. Fourier-transform infrared analysis did not show any physicochemical interaction between drug and carriers in solid dispersion formulation.

Conclusion: The hydrotrop is a novel and safe compound. It is a successful way to enhance the solubility of poorly aqueous soluble drugs. Immediate dissolution of practically insoluble drug nimodipine in dissolution media indicates that it has a great potential to solubilize the drug in biological fluids. Thus, a considerable improvement in bioavailability and onset of action of the drug can be predictable. Adding of a hydrotropic agent with nimodipine in solid dispersion increased the dissolution rate of the drug compared to the marketed conventional nimodipine tablet


Praveen K, Singh C. A Study on Solubility Enhancement Methods for Poorly Water-soluble drugs. AJPS 2013; 1(4):67–73.

Patravale VB, Date AA, Kulkarni RM. Nanosuspension: a promising drug delivery strategy. J Pharm Phamacol Res 2004; 56(7):827–40.

Sikarra D, Shukla V, Kharia AA, Chatterjee DP. Research article techniques for solubility enhancement of poorly soluble drugs: An overview. J Med Pharm Allied Sci 2012; 1:1–22.

Behera AL, Sahoo SK, Patil SV. Enhancement of solubility: A pharmaceutical overview. Pharm Lett 2010; 2:310–8.

Limbachiya MI, Agarwal M, Sapariya A, Soni S. Solubility enhancement techniques for poorly soluble drugs: Review. Int J Pharm Sci Rev Res 2011; 4:71–86.

Vemula V, Lagishetty V, Lingala S. Solubility enhancement techniques. Int J Pharm Sci Rev Res 2010; 5:41–51.

Shelke PV, Dumbare AS, Gadhave MV, Jadhave SL, Sonawane AA, Gaikwad DD. Formulation and evaluation of rapidly disintegrating film of amlodipine besylate. JDDT 2012; 2(2):72–5.

Chaudhari A, Nagachi U, Gulati N, Sharma VK, Khosa RK. Enhancement of solubilisation and bioavailability of poorly soluble drugs by physical and chemical modification: A recent review. JAPER 2012; 2(1):32–67.

Zaheer A, Naveen M, Santosh MK, Imran K, Solubility enhancement of poorly water-soluble drugs. Int J Pharma Tech 2011; 3(1):807–23.

Nidhi K, Indrajeet S, Khushboo M, Gauri K, Sen DJ. Hydrotropy: A promising tool for solubility enhancement: A review. Int J Drug Dev Res 2011; 3(2):26–33.

Dhapte V, Mehta P. Advances in hydrotropic solutions: An update review. St. Petersburg Polytechnical University. J Phy Math 2015;1:424–35.

Jain P, Goel A, Sharma S, Parmar M. Solubility enhancement techniques with special emphasis on hydrotrophy. Int J Pharma Professional’s Res 2010; 1(1):34–45.

Behera AL, Sahoo SK, Patil SV. Enhancement of solubility: a pharmaceutical overview. Der Pharmacia Lettre 2010; 2(2):310–8.

Sajid A. Solubility enhancement methods with importance of hydrotropy. JDDT 2012; 2(6):96–101.

Rao NG, Subhan M. Development of Nimodipine fast dissolving tablets: Effect of functionality of hydrophilic carrier on solid dispersion technique. JPBMS 2010; 8(10).

Maheshwari RK, Indurkhya A. Novel application of mixed hydrotropic solubilization technique in the formulation and evaluation of hydrotropic solid dispersion of aceclofenac. Asian J Pharma Sci 2010; 4(3):235–8.

Semcheddine F, Guissi NI, Liu XY, Wu ZM, Wang B. Effects of the preparation method on the formation of true Nimodipine SBE-β- CD/HP-β-CD inclusion complexes and their dissolution rates enhancement. AAPS Pharm Sci Tech 2015; 16(3):704–15.

Gorajana A, Nee N. Physicochemical characterization and in vitro evaluation of solid dispersions of nimodipine with PEG 8000. Asian J Chemistry 2011; 23(7):2857–9.

Patel S, Kumar D, Waghmode A, Dhabale A. Solubility enhancement of ibuprofen using hydrotropic agents. IJPLS 2011; 2(2):542–5.

Singh J, Umadevi SK, Vardhan S, Lachoriya M, Rajeswari G, Kasturibai B. Solubility enhancement of Candesartan cilexetil by using different hydrotropic agents. EJPMR 2015; 2(1):339–53.

Agrawal GP, Maheshwari RK, Mishra P. Preparation of solid dispersions of ornidazole using mixed hydrotropic solubilization technique and their characterization. Int J Green Pharm 2017; 11(4):715–20.

Rathinaraj B, Rajveer CH, Kumar P, Ganesh B, Shinde G. Studies on dissolution behavior of sustained release solid dispersion of nimodipine. Int J Pharma Sci Rev Res 2010; 3(1):77–82.

He Z, Zhong D, Chen X, Liu X, Tang X, Zhao L. Development of a dissolution medium for nimodipine tablets based on bioavailability evaluation. European J Pharm Sci 2004; 21:487–91.

Saibabu S, Pasam J, Ratnaraju K, Prathap M, Kumar Y. Formulation and evaluation of efavirenz immediate release tablets by using mixed hydrotropic soubilization technique. World Journal of Pharmacy and Pharmaceutical Sciences 2016; 5(2):1533–56.

Surwade K, Saudagar R. Solubility enhancement of azilsartanmedoxomil using mixed hydrotropy. World Journal of Pharmacy and Pharmaceutical Sciences 2015; 4(7):1167–79.

Jain R, Jain N, Jain S. Quantitative estimation of meloxicam: A novel approach using hydrotropic solubilization technique. Asian J Pharm Clinical Res 2013; 6(2):330–4.

Jain N, Jain R, Thakur N, Gupta BP, Banweer J, Jain S. Novel solubility enhancement technique hydrotropy. Int J App Pharm 2010; 2(3):11–4.

Jalali M, Ghenbarzadeh S, Adibkia K, Valizadeh H, Bibak S, Mohammadi G, et al. Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers. BioImpacts 2014; 4(3):141–8.

Guo Y, Shalaev E, Smith S. Physical stability of pharmaceutical formulations: solid-state characterization of amorphous dispersions. Trends Analyt Chem 2013; 49:137–44.

Rumondor ACF, Taylor LS. Application of Partial Least-Squares (PLS) modeling in quantifying drug crystallinity in amorphous solid dispersions. Int J Pharm 2010; 398:155–60.

Manogna K, Nagaveni P, Thyagaraju K. Enhancement of solubility of poorly soluble drugs by solid dispersion: An overview. Indian J Pharm Biot Res 2017; 5(4):17–23.

How to Cite
Ibrahim, N., Smail, S., Hussein, N., & Abdullah, T. (2020). Solubility enhancement of nimodipine using mixed hydrotropic solid dispersion technique. Zanco Journal of Medical Sciences (Zanco J Med Sci), 24(3), 386-394.
Original Articles