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This study investigated the effects of drug recrystallization on the in vitro performance of testosterone drug-in-adhesive transdermal delivery system (TDS). Six formulations were prepared with a range of dry drug loading in the adhesive matrix from 1% to 10% w/w with the aim of generating TDS with various levels of drug crystals. We visually quantified the amount of crystals in TDS by polarized light microscopy. The effect of drug recrystallization on adhesion, tackiness, cohesive strength, viscoelasticity, drug release, and drug permeation through human cadaver skin were evaluated for these TDS samples. The Optical images showed no crystals in 1% and 2% testosterone TDSs; however, the amount of crystals increased by increasing testosterone loading from 4 to 10%. A proportional and significant decrease (p < 0.05) in tack, peel, and shear strength of the adhesive matrix with increasing amount of crystals in TDS was observed. The drug crystals resulted in a proportional deterioration of the viscoelastic properties of the adhesive matrix. The 2% testosterone TDS showed faster drug release rate when compared to 1% testosterone TDS. The increase in drug loading from 2% to 4% w/w slightly increased the cumulative amount of testosterone released. Further increase in drug loading in TDS to 6, 8, and 10% was nonsignificant (p > 0.05) to affect the drug release and permeation. In conclusion, this study demonstrated that the extent of drug recrystallization can be quantitatively correlated with the deterioration of performance characteristics of TDS products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The Center for Drug Evaluation and Research (CDER) within the US Food and Drug Administration (FDA) is tracking the use of nanotechnology in drug products by building and interrogating a technical profile of products containing nanomaterials submitted to CDER. In this Analysis, data from more than 350 products show an increase in the submissions of drug products containing nanomaterials over the last two decades. Of these, 65% are investigational new drugs, 17% are new drug applications and 18% are abbreviated new drug applications, with the largest class of products being liposomal formulations intended for cancer treatments. Approximately 80% of products have average particle sizes of 300 nm or lower. This analysis identifies several trends in the development of drug products containing nanomaterials, including the relative rate of approvals of these products, and provides a comprehensive overview on the landscape of nanotechnology application in medicine.

At the Product Quality Research Institute (PQRI) Workshop held last January 14-15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.

The Nanotechnology Risk Assessment Working Group in the Center for Drug Evaluation and Research (CDER) within the United States Food and Drug Administration was established to assess the possible impact of nanotechnology on drug products. The group is in the process of performing risk assessment and management exercises. The task of the working group is to identify areas where CDER may need to optimize its review practices and to develop standards to ensure review consistency for drug applications that may involve the application of nanotechnology. The working group already performed risk management exercises evaluating the potential risks from administering nanomaterial active pharmaceutical ingredients (API) or nanomaterial excipients by various routes of administration. This publication outlines the risk assessment and management process used by the working group, using nanomaterial API by the oral route of administration as an example.