Effects of Preservatives in Nasal Formulations on the Mucosal Integrity: An Electron Microscopic Study

Abstract

The preservatives benzalkonium chloride (BZC) and potassium sorbate (PS) are widely used in the formulation of nasal drops and cosmetics. Recently, a number of side effects that resulted from mucosal irritation caused by BZC and PS have been reported. Therefore, this study was performed to investigate the possible clinical and histological alterations induced by in vivo administration of these preservatives to the nasal mucosa of rats. 0.01% BZC and 0.12% PS were administered to the nostrils of male rats for 1 or 4 weeks. Clinical symptoms were recorded during the treatment, and light and electron microscopic examinations were carried out on samples taken from one third central and lower regions of the noses at the end of the treatment periods. Symptomatic changes such as sneezing and nasal rubbing were observed in almost all groups, starting from the 6th day of administration. Light and electron microscopy showed histological changes and nasal lesions induced by the preservatives. The symptomatic and histological changes were more pronounced with prolonged duration of administration. Therefore, it has been concluded that in vivo administration of the preservatives BZC and PS may be irritant to the respiratory epithelium of rats.

Beneficial effect of antibiotics on ciliary beat frequency of human nasal epithelial cells exposed to bacterial toxins

“…As, in-vivo, the solutions would be diluted by the presence of mucus, we also studied more dilute concentrations of the antibiotics for which a cilio-stimulatory effect was observed. After a ten-fold dilution (which has been described as clinically relevant (Lebe et al 2004)), bacitracin, clindamycin, gramicidin and roxithromycin still exhibited a cilio-stimulatory effect. For bacitracin and clindamycin, the effect on CBF was slightly lower, while for gramicidin and roxithromycin there was no decrease in response on dilution (Table 1).…”

Considerations for the Development of Nasal Dosage Forms

“…In certain cases, preservatives affected the cilia in the nasal cavity by altering the elimination of the nasal mucus (in cases of nasal infection) and slowing down or even stopping mucociliary clearance, an essential natural mechanism for protecting the upper airways. Several reviews have examined adverse events associated with the use of preservatives (Lebe et al 2004 ;Mallants et al 2007 ;Bernstein 2000 ;Merkus et al 2001 ;van de Donk et al 1980van de Donk et al , 1982. Preservatives also introduce formulation challenges due to drug stability/drugdevice compatibility issues, and/or by modifying the smell and/or taste of the nasal drug products.…”

Evaluation of Histopathological Changes of Long-Term Use of Sodium Cromoglycate on Healthy Rat Nasal Respiratory Mucosa with Light Microscopy

“…Ayrıca burunlarına koruyucu madde (benzalkonyum klorid ve potasyum sorbat) tatbik edilen sıçanlarda kullanım süresine bağlı olarak, belirli bir süreden sonra hapşırma, burun kaşıma gibi semptomplar ortaya çıkartmıştır. Bu sıçanların burunları ışık mikroskobu ile incelendiğinde skuamöz metaplazi, silia kaybı, inflammasyon, ödem, damar yapısında değişiklik görülmüştür (11). Bizim ça-lışmamızda da skuamöz metaplazi, silia kaybı ve azalmış epitelyum kalınlığı saptanmıştır.…”