The course is addressed to create a know-how on the development of the pharmaceutical product with particular reference to: preformulation studies, stability of pharmaceutical formulations, impurities, drug-excipient interactions, microbiological quality, GMP and intellectual property.
Pharmaceutical research and development: the drug development process; discovery, lead optimization, preclinical research, clinical research, pharmacokinetic study, formulation development; drug registration and marketing authorization.
Preformulation: definition, main parameters. Solubility and factors affecting solubility (pH, temperature, addition of a solvent, complexation (mechanism and phase diagrams), micellar solubilization.
Drug dissolution: mechanism and factors affecting dissolution rate; Noyes-Withney equation.
Partition coefficient; effect of pH. Dissociation constant.
Physical characteristics of solids: crystallinity and polymorphism, size, chemical stability. Hygroscopicity. Analysis techniques.
Drug stability. Drug degradation processes: hydrolysis (influencing factors and stabilization) Oxidation (mechanism, factors increasing oxidation, methods to prevent or delay oxidation; antioxidants and their characteristics. Isomerization and racemization. Polymerization.
Kinetics of degradation processes: reaction rate. The zero order reaction and pseudo-zero order reaction. First order reactions and pseudo-first order reactions. Second order reactions. Methods of determination of order of reaction. Complex reactions: reversible, parallel, consecutive. Factors influencing reaction rate: pH, temperature, ionic strength, co-solvent surfactants.
Stability testing: long term and accelerated testing. ICH Guidelines: storage conditions, testing frequency, selection of batches, significant change, in-use stability.
Photostability. Mechanisms of photodegradation. Factors affecting photodegradation. Photoprotection. Photostability studies of solutions, semisolid and solid dosage forms. Kinetics of drug photoreactions. The ICH photostability Guidelines. Irradiation sources, exposure level, presentation of samples.
Impurities in new drug substances and new drug products. ICH Guidelines (Q3A, Q3B) and Ph. Eur. Residual solvents. ICH Guideline (Q3C) and Ph. Eur.. Solvents classification. Assessment of exposure levels.
Elemental impurities. ICH Guidelines (Q3D). Drug-excipient interaction and incompatibility. Impurities of the excipients. Compatibility of pharmaceutical product and container.
Quality of Biotecnological products. ICH Guidelines (Q5A-Q5E).
Microbiological quality. Ph. Eur., ICH Guidelines. Microbiological quality of non-sterile products: microbial count. Micorbiological quality of drug and pharmaceutical product non-sterile. Preservative efficacy. Preservation of pharmaceutical products. Preservatives and factor affecting their efficacy. Characteristics of some preservatives (benzalkonium chloride, parabens, benzoic acid, chlorbutanol.). Alternative methods for microbiological quality control: bioimpedence, bioluminescence, flow cytometry.
GMP. Regulatory framework. EU GMP structure and main concepts. EU GMP Annex 1 Controlled contamination environments. Qualification / validation. Support systems. The evolution of the GMPs. Risk Management.
Intellectual property. Patents and other forms of property protection. Invention and fundamental characteristics. Rights conferred by the patent. Practices that make up a patent application. Advantages and disadvantages of the patent. Alternatives.