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

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Abstract

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.

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Most cited references 18

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Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy.

R S Irwin, W M Corrao, M R Pratter (1981)

Using a diagnostic protocol based on the anatomy and distribution of cough receptors and afferent nerves, we sought to determine the causes and outcome of specific therapy of chronic persistent cough in 49 consecutive and unselected patients. A specific diagnosis was made in all. Cough was due to chronic postnasal dip from a variety of conditions in 29%, asthma in 25%, postnasal drip plus asthma in 18%, chronic bronchitis in 12%, gastroesophageal reflux in 10%, and miscellaneous disorders in 6%. History, physical examination, and methacholine inhalational challenge diagnosed disease in 86% of all patients. Adjusted success rates for specific therapy, and average of 4.4 and 18.9 months after therapy had been prescribed, were 98% and 97%, respectively. We concluded the following about chronic persistent cough; using an anatomic, diagnostic protocol, the cause can be consistently determined; postnasal drip and/or bronchial asthma are very common causes of cough; the outcome of specific therapy, almost without exception, is successful and sustained.

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Female gender as a determinant of cough threshold to inhaled capsaicin.

M Naruse, Amy K. Kasahara, T. Hashimoto … (1996)

Chronic, nonproductive cough and cough associated with the use of angiotensin converting enzyme inhibitors, are more frequently observed in females as compared to males. To examine the influence of sex, age, height, weight and pulmonary function on airway cough sensitivity, cough threshold to inhaled capsaicin, an index of the airway cough sensitivity, was measured in 160 nonsmoking, nonatopic healthy subjects. Forty young males (aged 24 +/- 2 yrs) 40 young females (aged 22 +/- 2 yrs) 40 middle-aged males (aged 48 +/- 5 yrs) and 40 middle-aged females (aged 50 +/- 7 yrs) were studied. The cough threshold was defined as the lowest concentration of inhaled capsaicin causing five or more coughs. The cough threshold was 3-5 fold lower in females than in males both in young (p<0.001) and middle-aged (p<0.005) subjects. Cough threshold was weakly but significantly correlated to height, weight, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) when all subjects were considered together but not when each group was considered separately. Multiple regression analysis revealed that sex difference was the significant predictive factor for the cough threshold in either age group. These results confirm that cough sensitivity is heightened in females and suggest that influence of height and pulmonary function on the cough threshold may have resulted from sex difference.

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Capsaicin cough sensitivity decreases with successful treatment of chronic cough.

Sanjeev V. Thomas, F O'Connell, Nicholas R. Fuller … (1994)

To assess the role of enhanced cough sensitivity in the pathogenesis of cough, we measured cough severity on a visual analogue scale (VAS) and capsaicin cough sensitivity (the concentration required to elicit two [C2] and five [C5] coughs) in 87 consecutive patients referred with chronic cough. Measurements were repeated after complete investigation and treatment, when patients were entered into one of four study groups: (1) treatment success (primary cause of cough successfully treated with elimination of the cough, n = 48); (2) primary treatment failure (treatment of potential primary cause of cough unsuccessful, n = 12); (3) cough treatment failure subgroup A (potential primary cause of cough identified and successfully treated but no improvement in cough, n = 8); and (4) cough treatment failure subgroup B (no potential primary cause of cough identified, n = 19). All patients in groups 3 and 4 were nonsmokers, had normal chest radiography and negative histamine challenge test, and failed to respond to intensive empirical treatment for rhinitis and gastroesophageal reflux. The VAS cough severity was lower and log C2 and C5 higher after treatment compared with initial values in the treatment success group but not in the other three groups. Enhanced sensitivity of airway nerves that mediate cough is important in the pathogenesis of nonproductive cough, and successful treatment is associated with a reduction in cough sensitivity. While enhanced sensitivity of airway nerves is usually present in patients with identifiable causes of chronic nonproductive cough, it is also found in other patients in whom the cause of cough is unknown.

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Author and article information

Contributors

Michael T Costanzo

Richard A Yost

Paul W Davenport

Journal

Journal ID (nlm-ta): Cough

Journal ID (iso-abbrev): Cough

Title: Cough (London, England)

Publisher: BioMed Central

ISSN (Electronic): 1745-9974

Publication date Collection: 2014

Publication date (Electronic): 25 September 2014

Volume: 10

Page: 6

Affiliations

[1 ]Department of Chemistry, University of Florida, Gainesville, FL 32611, USA

[2 ]Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, USA

Article

Publisher ID: 1745-9974-10-6

DOI: 10.1186/1745-9974-10-6

PMC ID: 4194457

PubMed ID: 24552215

SO-VID: 5ff2b4d8-c376-48f3-8f36-ba54415ce6c1

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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

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Abstract

Background

Methods

Results

Conclusion

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Inflamed lung in vitro co-culture models

Most cited references 18

Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy.

Female gender as a determinant of cough threshold to inhaled capsaicin.

Capsaicin cough sensitivity decreases with successful treatment of chronic cough.

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