RISK-ORIENTED STRATEGY FOR THE DEVELOPMENT OF THE COMPOSITION AND TECHNOLOGY OF SOLID DISPERSION SYSTEMS
DOI:
https://doi.org/10.35546/kntu2078-4481.2025.1.1.21Keywords:
solid dispersion systems, pharmaceutical development, quality target product profile, critical quality indicators, risk assessmentAbstract
For the first time, the problem of increasing the solubility of APIs in solid pharmaceutical systems by creating a polymeric composite material with regard to its target drug quality profile is comprehensively considered. An algorithm for conducting research at the preformulation stage is proposed. Experimental data are shown on the examples of mefenamic acid and rivaroxaban. The risk factors for a product based on a solid dispersion system are identified, and the risks to the quality of the drug manufacturing process in a pharmaceutical enterprise are assessed. The potential critical quality indicators of the drug are indicated and their criticality is assessed. The critical quality indicators of the initial components and product properties are identified and described. The most probable risks to the quality of the drug at the stage of pharmaceutical development are identified, analysed and assessed. The risk factors that are specific to the process under study and affect the quality of the drug manufacturing process are identified and substantiated. It has been determined that for the products under study, disintegration, dissolution, accompanying impurities, quantification and homogeneity of dosage units are identified as critical quality characteristics that can potentially affect the quality of the drug. It is described that the risk factors for the investigated drug are the solid dispersion system, manufacturing formulation, technological process, packaging system and quality control methods. It is shown that the stages of preparation of tablet mass and packaging, packing and labelling of the production process have a significant degree of risk, which is acceptable. It is proved that the use of risk assessment allows a reasonable approach to the development and production process while minimising the amount of material and time resources.
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