Standardized method for solubility and storage of capsaicin-based solutions for cough induction

Cough

Paul W Davenport²  Richard A Yost¹  Michael T Costanzo¹ 

[1] Department of Chemistry, University of Florida, Gainesville, FL 32611, USA;Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, USA

关键词: UV detection;    Tussigenic challenge;    Stability;    Solubility;    Capsaicin;   

Others  :  1145254
DOI  :  10.1186/1745-9974-10-6

 received in 2013-04-11, accepted in 2014-04-24,  发布年份 2014

【 摘 要 】

Background

Preparation of inhaled capsaicin solutions for cough induction varies greatly from one lab to another, which creates inconsistencies between tussigenic challenge results. The addition of Tween to these capsaicin solutions provides increased solubility and stability; however, the foul taste of Tween makes inhaling the solution for any prolonged period of time unpleasant. We sought to create a standard method for preparing soluble and stable capsaicin-based solutions (in 10% ethanol/water), without the addition of Tween.

Methods

Capsaicin solutions were created at concentrations ranging from 0 to 500 μM in a variety of solvent systems, with and without Tween. Samples were stored in four different environments (-20°C, 3°C, and room temperature, protected from light; and room temperature, exposed to light) to test stability. Detection of capsaicin was carried out by UV absorption. A Grubb’s test was performed on all data to remove statistical outliers.

Results

Similar capsaicin concentrations were seen for solutions prepared with or without Tween (Tween provided a slight increase in solubility), with neither solvent system providing complete solubility. Of the four environments tested, storing capsaicin solutions at 3°C while protected from light afforded the greatest stability, for a minimum of 30 weeks.

Conclusion

We recommend the use of a 10% ethanol/water solvent system without Tween in the preparation of capsaicin solutions for tussigenic challenges. While this solvent system does not provide complete solubility, we have detailed a method for capsaicin solution preparation that will account for this loss of solubility, while maintaining a solution that is Tween-free and safe for human inhalation.

【 授权许可】

   
2014 Costanzo et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]O'Connell F, Thomas VE, Pride NB, Fuller RW: Capsaicin cough sensitivity decreases with successful treatment of chronic cough. Am J Respir Crit Care Med 1994, 150:374-380.
• [2]Fuller RW: Pharmacology of inhaled capsaicin in humans. Respir Med 1991, 85:31-34.
• [3]Irwin RS, Corrao WM, Pratter MR: Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. Am Rev Respir Dis 1981, 123:413-417.
• [4]Turgut C, Newby B, Cutright TJ: Determination of optimal water solubility of capsaicin for its usage as a non-toxic antifoulant. Environ Sci Pollut Res Int 2004, 11:7-10.
• [5]O’Neil MJ (Ed): The Merck Index In Encyclopedia of Chemicals, Drugs, and Biologicals (14th edition). Whitehouse Station, NJ: Merck Research Laboratories; 2006.
• [6]Kopec SE, DeBellis RJ, Irwin RS: Chemical Analysis of Freshly Prepared and Stored Capsaicin Solutions: Implications for Tussigenic Challenges. Pulm Pharmacol Ther 2002, 15:529-534.
• [7]Kopec SE, Irwin RS, Debellis RJ, Bohlke MB, Maher TJ: The effects of Tween-80 on the integrity of solutions of capsaicin: useful information for performing tussigenic challenges. Cough 2008, 4:3. BioMed Central Full Text
• [8]Fujimura M, Kasahara K, Kamio Y, Naruse M, Hashimoto T, Matsuda T: Female gender as a determinant of cough threshold to inhaled capsaicin. Eur Respir J 1996, 9:1624-1626.
• [9]Fujimura M, Kasahara K, Yasui M, Myou S, Ishiura Y, Kamio Y, Hashimoto T, Matsuda T: Atopy in cough sensitivity to capsaicin and bronchial responsiveness in young females. Eur Respir J 1998, 11:1060-1063.
• [10]Davenport PW, Sapienza CM, Bolser DC: Psychophysical assessment of the Urge-to-Cough. Eur Respir Rev 2002, 12:249-253.
• [11]Dicpinigaitis PV, Allusson VR, Baldanti A, Nalamati JR: Ethnic and gender differences in cough reflex sensitivity. Respiration 2001, 68:480-482.
• [12]Dicpinigaitis PV, Alva RV: Safety of capsaicin cough challenge testing. Chest 2005, 128:196-202.
• [13]Vovk A, Bolser DC, Hey JA, Danzig M, Vickroy T, Berry R, Martin AD, Davenport PW: Capsaicin exposure elicits complex airway defensive motor patterns in normal humans in a concentration-dependent manner. Pulm Pharmacol Ther 2007, 20:423-432.
• [14]Baeyens F, Hendrickx H, Crombez G, Hermans D: Neither extended sequential nor simultaneous feature positive training result in modulation of evaluative flavor-flavor conditioning in humans. Appetite 1998, 31:185-204.
• [15]Coppens E, Vansteenwegen D, Baeyens F, Vandenbulcke M, Van PW, Eelen P: Evaluative conditioning is intact after unilateral resection of the anterior temporal lobe in humans. Neuropsychologia 2006, 44:840-843.
• [16]Dickinson A, Brown KJ: Flavor-evaluative conditioning is unaffected by contingency knowledge during training with color-flavor compounds. Learn Behav 2007, 35:36-42.
• [17]Skoog DA, Holler FJ, Crouch SR: Principles of Instrumental Analysis. 6th edition. Thomson Brooks/Cole: Belmont, CA; 2007.
• [18]Midgren B, Hansson L, Karlsson JA, Simonsson BG, Persson CGA: Capsaicin-induced cough in humans. Am Rev Respir Dis 1992, 146:347-351.
• [19]Hegland KW, Bolser DC, Davenport PW: Volitional control of reflex cough. J Appl Physiol 2012, 113:39-46.
• [20]Hegland KW, Troche MS, Davenport PW: Cough expired volume and airflow rates during sequential induced cough. Front Physiol 2013, 4:167.