Development of the method for quantitative determination of phenylephrine hydrochloride in the combined drops

Abstract

The work is devoted to development of the method for quantitative determination of phenylephrine hydrochloride in the combined nasal drops Gripocitron Rinis. Combination of phenylephrine hydrochloride possessing the vasoconstrictor action with dimetindene maleate having the antihistaminic action formulated into drops decreases nasal discharge and helps to clear the nasal passages without disturbing physiological functions of the ciliated epithelium and mucous membrane. It has been found that the quantitative content of phenylephrine hydrochloride in the combined nasal drops can be determined by spectrophotometry in the ultraviolet spectrum at the wavelength of 296 nm. The method proposed demonstrates the possibility of phenylephrine hydrochloride determination in combined drops in the presence of another active pharmaceutical ingredient – dimetindene maleate, which has the absorption minimum in sodium hydroxide solution at this wavelength. The influence of the additional ingredient – benzalkonium chloride drops on the nature of the absorption spectrum of phenylephrine hydrochloride is recommended to eliminate by the action of potassium dichromate solution. The optimal amount and concentration of solutions of sodium hydroxide and potassium dichromate, the analytical band have been determined. Validation of the given method has been carried out according to the following validation characteristics: linearity (a = 4.34 ≤ maxa 5.10%, b = 1.04), accuracy (0.52 ≤ maxδ 1.02%), convergence (1.07% ≤ max Δas 3.20%) and the correlation coefficient r, which is 0.9997. It has been found that the method suggested for determination of phenylephrine hydrochloride in nasal drops is precise, accurate, reproducible and linear, and it allows recommending it for using in pharmaceutical analysis. Phenylephrine hydrochloride is a known sympathomimetic providing a selective stimulating effect mainly on postsynaptic α-adrenergic receptors [4, 5]. Being a decongestant with a moderate vasoconstrictor action phenylephrine contains in a number of nasal drugs for local application, such as Nasol Baby (phenylephrine hydrochloride), Nasol Kids (phenylephrine hydrochloride with eucalyptol and benzalkonium chloride), Vibrocil and Gripocitron Rinis (phenylephrine hydrochloride with dimetindene maleate and benzalkonium chloride), which are used for symptomatic treatment of nasal congestion, acute and chronic rhinitis, allergic rhinitis, sinusitis, acute otitis. The search of safe and effective monocomponent and combined decongestant nasal drops for local application with phenylephrine hydrochloride actualizes development and standardization of methods for quality control of this substance in the presence of other active pharmaceutical ingredients (API) [3, 6, 7, 9]. Materials and Methods The object of the research was Gripocitron Rinis, nasal drops, 15 ml. The active substances were phenylephrine hydrochloride equivalent to 2.5 mg of phenylephrine, dimetindene maleate 0.25 mg; excipients were citric acid, monohydrate; anhydrous sodium hydrogen phosphate; sorbitol (Е 420); benzalkonium chloride; peppermint oil; purified water as needed. The reference standard (RS) of the substance of phenylephrine hy