Inhalation

INH0624

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Nasal powder formulations have emerged as an alternative dosage form in nasal drug delivery, offering a range of benefits compared to traditional aqueous sprays. These formulations are characterized by their simple composition, often utilizing no preservative and minimal excipients, to facilitate the administration of larger drug doses [1]. 10 June 2024 Inhalation Nasal powder: A stable, rapid-onset strategy for systemic therapy Utilizing particle engineering and novel devices to deliver shelf-stable, next-generation therapies William Wei Lim Chin, PhD a , Michael A. Sandoval, MSc b and Alan B. Watts, PhD a a Catalent Pharma Solutions b The University of Texas at Austin, College of Pharmacy Introduction Nasal powder formulations have emerged as an alter- native dosage form in nasal drug delivery, offering a range of benefits compared to traditional aqueous sprays. ese formulations are characterized by their simple composition, often utilizing no preservative and minimal excipients, to facilitate the administra- tion of larger drug doses [1]. is enhanced capacity for higher drug load combined with mucoadhesive properties directly contributes to improved diffu- sion and absorption across the mucosal surfaces, thereby significantly increasing bioavailability when compared to nasal liquids. Another key advantage of nasal powder formulations lies in their increased chemical stability due to reduced molecular mobility and water-facilitated degradation [2]. Unlike liquid formulations, they do not require preservatives since the solid state is less conducive to biological growth, making them more favorable to long-term storage and shipping. is stability can extend their effec- tiveness, as they remain potent without the need for refrigeration, eliminating cold chain requirements. Indications for nasal delivery Neurological disorders Building on the advantages of nasal powders, intra- nasal drug delivery has provided new opportunities for the treatment of neurological disorders. It pres- ents an effective and non-invasive method to bypass the blood-brain barrier, enabling direct delivery of therapeutic agents to the central nervous system (CNS). is approach has demonstrated promising outcomes in treating various neurological conditions, including Alzheimer's disease, depression, migraine and schizophrenia [3]. Vaccines and mucosal barriers Similarly, nasal vaccines have emerged as an effec- tive strategy in tackling respiratory infectious diseases, including COVID-19. ese vaccines provide dual immunity, both at the mucosal sur- faces and systemically, enhancing the body's defense mechanisms against pathogens. Although dry powder nasal vaccines are not yet commercially available [4], preclinical and clinical studies have demonstrated promising results for various anti- gens, including diphtheria, influenza, meningitis, anthrax, tetanus and viral gastroenteritis [5]. From a development and formulation perspective, nasal vaccines could be viewed as more straightfor- ward compared to pulmonary vaccines. With fewer concerns for localized toxicity than pulmonary deliv- ery [6], the nasal route may be more suitable for vac- cines, adjuvants and novel excipients. Moreover, the broader particle size distribution allowances for nasal powders compared to pulmonary powders provide a wider design space during powder manufacture by spray drying, enabling the selection of less denaturing process parameters [7]. However, the development of nasal vaccines is not without challenges. One signif- icant concern is the safety implications arising from the proximity of the nasal cavity to the CNS [8]. is necessitates careful evaluation of delivery systems to minimize potential deleterious effects on the CNS. Another strategy to combat viral infection, which often takes hold in the upper respiratory passages before spreading throughout the body, is using

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