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The nasal absorption of desmopressin was studied in two animal models, the rat and the sheep. The bioavailability after nasal administration was found to be 13 times higher in the rat model. This discrepancy is suggested to be due to the impaired mucociliary clearance mechanism in the rat model and possibly differences in enzymatic degradation and elimination rates of the drug. The effect of the addition of L-alpha-lysophosphatidylcholine (LPC) to the formulations as an absorption enhancer was most pronounced in the sheep model. The use of the bioadhesive starch microsphere delivery system, especially in combination with LPC, had a profound effect on the absorption of desmopressin in sheep, with bioavailabilities reaching nearly 10% compared with 1.2% for a simple nasal solution of desmopressin.

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The field of regulatory affairs deals with the regulatory requirements for marketing authorization of therapeutic products. This field is facing a myriad of forces impacting all aspects of the development, regulation and value proposition of new therapeutic products. Changes in global megatrends, such as geopolitical shifts and the rise of the green economy, have emphasized the importance of manufacturing and supply chain security, and reducing the environmental impacts of product development. Rapid changes due to advances in science, digital disruption, a renewed focus on the centrality of the patient in all stages of therapeutic product development and greater collaboration between national regulatory authorities have been accelerated by the COVID-19 pandemic. This article will discuss the various trends that are impacting the development of new therapies for alleviating disease and how these trends therefore impact on the role of the regulatory affairs professional. We discuss some of the challenges and provide insights for the regulatory professional to remain at the forefront of these trends and prepare for their impacts on their work.

The effects of several prospective absorption enhancers were assessed on the nasal absorption of biosynthetic human growth hormone (hGH) in the rat. These enhancers function by alternative mechanisms that include enzyme inhibition, reduction in mucus viscosity, and enhancement of membrane fluidity. The levels of plasma hGH achieved were determined by an enzyme-linked immunosorbent assay. The increase in peak height was calculated relative to nasal administration of hGH alone without any enhancers and the relative bioavailability was calculated with reference to subcutaneous injection data. A lysophospholipid, lysophosphatidylcholine, gave the highest peak concentration, with an increase in peak height of 450% and a relative bioavailability of 25.8%. However, the greatest increase in AUC (291%) was achieved with the aminopeptidase inhibitor, amastatin, which gave a relative bioavailability of 28.9%. A mucolytic agent, N-acetyl-L-cysteine, and a transmembrane fatty acid transporter, palmitoyl-DL-carnitine, were also found to promote the nasal absorption of hGH in this model, with relative bioavailabilities of 12.2 and 22.1%, respectively. Bestatin, an enzyme inhibitor, was not an effective absorption enhancer for hGH in this model.