Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for oral, while there are just a few for parenteral administration on the market. Parenteral forms are preferred in cases of postoperative indications, where rapid analgesic, anti-inflammatory and antipyretic action is required especially in patients with gastrointestinal problems and in patients with swallowing difficulties. Ibuprofen (IBP), which is classified in the NSAID group and is a representative of the widely used poorly soluble active pharmaceutical ingredient (API), was used in the experimental part of the doctoral thesis. US Food and Drug Administration (FDA) approved only one parenteral form with IBP with a concentration > 10 mg/mL, which is certainly due to the physicochemical properties of the molecule, especially poor water solubility (< 1 mg/mL), which in addition to the high dose (max. 800 mg daily) presents a great challenge to formulating dosage form with IBP. Numerous publications describe various techniques for IBP solubilization for solid dosage forms, while for parenteral forms solubility enchancment is less researched. The work of the doctoral thesis was divided into two parts. Firstly, the main focus was to develop a parenteral lyophilized product with enhanced solubility of IBP and isotonicity of the finally prepared solution after dissolving the lyophilisate with water for injections (WFI). We focused on the evaluation of the solution before lyophilization to define key process parameters and on the selection of excipients. Furtermore, as lyophilization is energy and time consuming technological process, its optimization was investigated. The influence of formulation and process parameters on the critical attributes of the final product was evaluated by multivariate data analysis (using the response surface method) and the optimal combination of formulation and process parameters was determined accordingly. In the second part of this thesis, the applicability of process analysis technology (PAT), namely near- infrared (NIR) and Raman spectroscopy for evaluation of critical attributes of the lyophilisate such as residual moisture content (RMC), specific surface area (SSA) and reconstitution time (RT) was evaluated. Multivariate data analysis (MVA), namely the principal components method (PCA) and partial least squares regression (PLS) were used for evaluation of the collected process data. The doctoral thesis consists of introduction part and three research papers that already are or will be published in recognised scientific journals.
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