Preformulation stability of Spantide II, a promising topical anti‐inflammatory agent for the treatment of psoriasis and contact dermatitis

Preformulation stability of Spantide II, a promising topical anti‐inflammatory agent for the... ABSTRACT Substance P is readily expressed in skin inflammatory disorders such as psoriasis and contact dermatitis. Spantide II is a peptide (MW 1668.76) that specifically binds to neurokinin‐1 receptor (NKR‐1) and blocks inflammation associated with substance P. The anti‐inflammatory property of Spantide II makes it a suitable candidate to be studied as a topical formulation for the treatment of dermal inflammatory disorders. The objective of this study was to investigate the influence of pH, temperature, salt concentration and concentration on the aqueous stability of Spantide II. The stability of Spantide II was also assessed by circular dichroic (CD) spectroscopy and mass spectrometry (MS). The influence of various dermatological vehicles (ethanol, Transcutol, propylene glycol, N‐methyl‐2‐pyrrolidone (NMP), ethyl oleate, isopropyl myristate and laurogylcol FCC (LFCC)) on the stability of Spantide II was investigated. A precise high‐performance liquid chromatography (HPLC) assay was developed for analysis of Spantide II. At higher temperature (40°C) the stability of Spantide II decreased with increase in pH (P < 0.05). Change in salt concentration did not appreciably affect the stability of Spantide II (P > 0.05). The concentration of Spantide II in the solution had no significant influence on its stability (P > 0.05). CD spectroscopy studies showed that Spantide II has a relatively stable α‐helix structure in the liquid state. The stability of Spantide II was affected by the type of vehicle used in the study (P < 0.01) at different temperatures (P < 0.05). Spantide II at high temperature undergoes lysine–proline diketopiperazine degradation as evident in MS data. Spantide II was relatively more stable in ethyl oleate–ethanol, ethanol–water, ethanol and N‐methyl‐2‐pyrrolidone. The results of this study indicate that ethyl oleate–ethanol (1:1) and ethanol–water (1:1) could be used as potential vehicles in the development of topical formulations of Spantide II. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Pharmacy and Pharmacology: An International Journal of Pharmaceutical Science Wiley

Preformulation stability of Spantide II, a promising topical anti‐inflammatory agent for the treatment of psoriasis and contact dermatitis

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Publisher
Wiley
Copyright
2004 Royal Pharmaceutical Society of Great Britain
ISSN
0022-3573
eISSN
2042-7158
D.O.I.
10.1111/j.2042-7158.2004.tb02573.x
Publisher site
See Article on Publisher Site

Abstract

ABSTRACT Substance P is readily expressed in skin inflammatory disorders such as psoriasis and contact dermatitis. Spantide II is a peptide (MW 1668.76) that specifically binds to neurokinin‐1 receptor (NKR‐1) and blocks inflammation associated with substance P. The anti‐inflammatory property of Spantide II makes it a suitable candidate to be studied as a topical formulation for the treatment of dermal inflammatory disorders. The objective of this study was to investigate the influence of pH, temperature, salt concentration and concentration on the aqueous stability of Spantide II. The stability of Spantide II was also assessed by circular dichroic (CD) spectroscopy and mass spectrometry (MS). The influence of various dermatological vehicles (ethanol, Transcutol, propylene glycol, N‐methyl‐2‐pyrrolidone (NMP), ethyl oleate, isopropyl myristate and laurogylcol FCC (LFCC)) on the stability of Spantide II was investigated. A precise high‐performance liquid chromatography (HPLC) assay was developed for analysis of Spantide II. At higher temperature (40°C) the stability of Spantide II decreased with increase in pH (P < 0.05). Change in salt concentration did not appreciably affect the stability of Spantide II (P > 0.05). The concentration of Spantide II in the solution had no significant influence on its stability (P > 0.05). CD spectroscopy studies showed that Spantide II has a relatively stable α‐helix structure in the liquid state. The stability of Spantide II was affected by the type of vehicle used in the study (P < 0.01) at different temperatures (P < 0.05). Spantide II at high temperature undergoes lysine–proline diketopiperazine degradation as evident in MS data. Spantide II was relatively more stable in ethyl oleate–ethanol, ethanol–water, ethanol and N‐methyl‐2‐pyrrolidone. The results of this study indicate that ethyl oleate–ethanol (1:1) and ethanol–water (1:1) could be used as potential vehicles in the development of topical formulations of Spantide II.

Journal

Journal of Pharmacy and Pharmacology: An International Journal of Pharmaceutical ScienceWiley

Published: Jan 1, 2004

References

  • Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems
    Scholzen, Scholzen; Armstrong, Armstrong; Bunnett, Bunnett; Luger, Luger; Olerud, Olerud; Ansel, Ansel
  • Instability, stabilization and formulation of liquid protein pharmaceuticals
    Wang, Wang

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