European Journal of Pharmaceutics and Biopharmaceutics最新文献

Between 2018 and 2021, losartan was the most often recalled product (24% of total recalls) followed by metformin tablets (19% of total recalls) due to the presence of nitrosamine impurities. The objective of this work is to analyse the de-risking method in terms of reducing nitrosamine generation and establishing nitrite specifications in excipients. In light of these recalls, we simulated the influence of post-approval level 1 and level 2 changes in excipient compositions on nitrosamine formation in metformin SR (sustained release) and losartan film coated tablets. Furthermore, we investigated the de-risking approach in terms of reducing nitrosamine formation and establishing nitrite specifications in excipients. Level 1 changes in excipient composition resulted in no discernible increase in nitrosamine impurities for both metformin SR and losartan film coated tablets. On the other hand, level 2 changes resulted in more than 7% and 18% increase in nitrosamine levels in metformin SR and losartan film coated tablets, respectively. In fact, level 2 changes could cause nitrosamine impurities to exceed the AI (acceptable intake) limits. When low-nitrite level (LNL) excipients were employed, level 2 changes resulted in no significant increase in nitrosamine formation from their original values. Finally, specifications for nitrite in excipients were established. Selecting formulation excipients with LNLs is critical for risk mitigation as was demonstrated in this study. To continue enjoying the regulatory flexibility in terms of reducing post approval variation submissions, it is paramount to assess the impact of nitrite load of excipients on the total nitrosamine burden of the product during product development.

Solar radiation impacts the skin's biological processes, leading to premature aging. Accurately identifying and evaluating these effects in humans through tissue-based models is essential for advancing anti-aging research and validating cosmetic ingredients claims. However, the existing literature remains highly fragmented, hindering the identification of suitable photoaging skin models and knowledge gaps. This work provides a comprehensive and up-to-date review of human (clinical and ex vivo) photoaging skin models used to assess the anti-aging efficacy of cosmetic ingredients, paving the way for the development of more advanced models for this purpose. A total of 43 studies using human skin (24 clinical and 19 ex vivo studies) were identified and curated. Clinical studies capture integrated physiological responses, in their majority associated with the improvement of clinical manifestations, whereas ex vivo models enable controlled mechanistic assessments of cellular and molecular changes. The key biomarkers evaluated in these studies encompass the main hallmarks of skin aging, including inflammation, oxidative stress, cellular senescence, and structural alterations. In recent years, the assessment of photo-induced alterations in skin fibers and oxidation products has improved considerably due to the advances in the spectroscopic techniques in clinical studies. Despite these advances, variability in exposure conditions, biomarker selection, and phototype representation thwarts deeply cross-study comparisons. Future progress should focus on incorporating a broader range of Fitzpatrick phototypes, optimising irradiation conditions to approximate to the chronic solar exposure and integrating new biomarkers such as advanced glycation end-products and immunosuppressive indicators. The implementation of emerging technologies, such as skin-on-a-chip systems, and microfluidics, could enhance physiological relevance and reproducibility. Overall, this review identifies the key findings, highlighting strengths and limitations of the models, and future priorities towards the development and implementation of accurate human skin models for assessing anti-aging efficacy.

Patient-friendly solid oral dosage forms remain a rather understudied part of pharmaceutical development, particularly in paediatric patients. Thus, patients and caregivers around the world must resort to traditional approaches, such as liquid dosage forms or division of solid dosage forms, which can lead to inaccurate dosing and drug inactivation. To avoid these issues, as well as the swallowing problems and choking risk of conventional solid oral dosage forms, there is a need for modern, safe and effective oral dosage forms. Orodispersible tablets enhance the ease of administration for patients with deglutition difficulties, but their use is typically confined to immediate-release delivery systems. In this study, we addressed these shortcomings by developing orodispersible tablets as delivery platform for oral administration of loratadine-loaded zein-based nanostructures to paediatric patients. First, the nanostructures were freeze-dried with mannitol and maltodextrin as cryoprotectants. The resulting powders were compressed as such or mixed with different ratios of co-processed excipients for orodispersible tablets, in order to understand their compression behaviour. To ensure dose uniformity and powder homogeneity, a near infrared spectroscopic method was developed for non-destructive assessment of the API content. With the aid of the co-processed excipients and supplementary lubrication to reduce the tablet ejection stress, tablets with adequate mechanical properties and a disintegration time within the required range of 180 s were obtained from the nanostructures lyophilised with mannitol. Through this methodology, we have transformed loratadine-based nanosystems into an innovative and patient-friendly oral delivery system that meets the specific quality requirements of orodispersible pharmaceutical forms.