Considerations for the Development of Nasal Dosage Forms

Abstract

The anatomy and physiology of the nasal cavity provide unique advantages for accessing targets for local, systemic, and potentially central nervous system drug delivery. This chapter discusses these advantages and the challenges that must be overcome to reach these targets. The chapter then comprehensively reviews nasal dosage forms, analytical testing, and regulatory requirements in the context of existing nasal spray products. Since nasal sprays are moving towards being preservativefree, the chapter covers specialized methods of achieving a sterile product, namely, formulation strategies, manufacturing strategies, and the device landscape that support this upcoming platform. Finally, the chapter reviews various pathways for regulatory approval around the world, for brand and generic, with particular emphasis on the growing acceptance of in vitro data for locally acting nasal spray products.

Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures?

“…In the US, in November 2015, the FDA granted approval to a naloxone nasal spray which we understand to be a concentrated nasal spray delivering a 4mg naloxone dose in a 0.1ml volume through what appears to be an Aptar single‐dose liquid nasal spray device . This approval was issued while this ‘For Debate’ was in press, but we have had opportunity to add brief consideration.…”

Letters toAddictionfrom Coffinet al.and Doe-Simpkinset al.re: ‘For Debate’ on clinical use of improvised nasal naloxone sprays: authors’ response

“…We have considered this briefly elsewhere where we have noted that Ehrick et al . do not consider it as a significant route of nasal absorption in man , and that Djupesland et al . conclude that human evidence of direct drug transport from the nose to the cerebrospinal fluid is currently still lacking .…”

Using the Intranasal Route to Administer Drugs to Treat Neurological and Psychiatric Illnesses: Rationale, Successes, and Future Needs

“…In 2002 the US Food and Drug Administration (FDA) released documentation on the best practices for the chemistry and manufacturing controls of nasal spray solutions and suspensions. In the following section, we summarize those considerations with respect to each component of a typical IN formulation [ 89 ].…”