Application of a mixture DOE for the prediction of formulation critical temperatures during lyophilisation process optimisation.

During lyophilisation cycle design, primary drying parameters (chamber pressure and shelf temperature) are adjusted to maximize the sublimation rate and prevent cake collapse, by maintaining the product continuously below its critical temperatures. The objective of this study was to employ mixture design of experiments to generate empirical models capable of predicting glass transition of the maximally freeze concentrated solution (Tg') and collapse temperature (Tc) of amorphous protein (BSA and IgG1) formulations. Additionally, the models developed aid the design of high concentration protein formulations with maximised critical temperatures to obtain shorter and more cost-effective lyophilisation cycles. Formulations contain sucrose as cryo/lyo-protectant and arginine/arginine-HCl as multifunctional excipient (e.g. solubility enhancer, viscosity and aggregation suppressor). The impact of formulation components at varied ratios on critical temperatures was evaluated; the amorphous excipients decrease critical temperatures, on the contrary, the protein increases critical temperatures. The robustness of the empirical models generated with BSA formulations was verified with BSA and IgG1 formulations. The models showed greater accuracy in predicting Tg' than the Fox-Flory equation. For the first time, empirical models are reported to predict both critical temperatures. Finally, unconventional collapse events observed for formulations with and without arginine/arginine-HCl at different protein concentrations are also discussed.

Parenteral protein formulations: An overview of approved products within the European Union.

The study presented is a comprehensive overview of commercial parenteral protein formulations, approved by the European Medicines Agency (EMA), 1995-2018. The objective of this overview was to analyse current trends in the design of commercial parenteral protein products and thereby support formulation scientists in the design of new formulations. The main data source was the publicly available European Public Assessment Reports (EPARs) published by the EMA for each authorised product. An analysis of the percentage of formulations in a liquid and lyophilised form was conducted. In addition, the number of products containing individual excipients, classified into functional categories is provided. Finally, the overview includes comprehensive details of product compositions obtained from EMA, US Food and Drug Administration (FDA) and product Marketing Authorisation Holder. Data analysis highlighted trends in the number of products approved, and the higher percentage of liquid parenteral protein formulations (66%) compared to lyophilised formulations (34%). This overview identifies the most commonly incorporated excipients employed as buffering agents, stabilisers/bulking agents, surfactants, preservatives and tonicifiers, including their concentration ranges of use in both liquid and lyophilised formulation approaches. Finally, antibody-based formulations were a particular focus of this overview. The relationship between parenteral routes of administration and antibody concentrations in approved products was also investigated.

Granuloma actinico. / Actinic granuloma

Se presenta un caso de granuloma actinico.Se efectua una revision bibliografica del tema y se discute el factor etiologico

Granuloma actinico. / Actinic granuloma

Se presenta un caso de granuloma actinico.Se efectua una revision bibliografica del tema y se discute el factor etiologico