Toxicological Implications of Nasal Formulations

• Published in: Drug delivery 1999, Vol.6 (4), p.227-242
• Main Author: Muhammad Quadir, Hossein Zia, Thomas E. Needham
• Format: Article
• Language: English
• ISSN: 0049-8254; 1071-7544; 1366-5928; 1521-0464
• DOI: 10.1080/107175499266823

Various nasal formulations have been tested for their suitability to deliver drugs through the nasal cavity. This route is especially of interest where the dose of drug is small and the drug may undergo an extensive first-pass metabolism and/or decomposition while passing through the gastrointestinal tract. Unfortunately, the nasal mucosa does not have same type of tolerability to all drugs and additives used in formulations. Some chemicals may damage the nasal epithelia or alter the mucociliary defensive mechanism of the nose. There also is a possibility that the drug can transport directly from nasal cavity to the brain via the olfactory route. Several methods have been developed to study the impact of drugs and excipients on the integrity of the nose. In some cases, the in vitro results did not correlate well with in vivo data, due to lack of reproducibility of the natural body environment, and some in vitro methods may not be sensitive enough and thus may complicate interpretation of the results. This review provides a toxicological evaluation of different drugs and additives used to optimize a nasal formulation. Certain chemicals are now routinely used as additives in nasal formulations. Although these compounds are most likely safe, if they are used over the long term, they may damage the epithelia of the nose. For multidose preparations, preservatives are often included in nasal delivery systems and may cause ciliotoxic effects. Both physicochemical parameters of drugs as well as formulation materials should be considered in evaluating the overall effect ofa drug product on the nose. Therefore, any prior knowledge of the effect of drugs and additives on the nasal epithelia ultimately will assist in the development of nasal products. Furthermore, as the sites of absorption in the nasal cavity are somewhat limited, evaluation of the long-term tolerability of a nasal formulation is of great importance.