Course program
PRINCIPLES OF BIOPHARMACEUTICS AND PHARMACOKINETICS. Introduction to Biopharmaceutics. The LADME system. Main drug administration routes. Focus on absorption. Physicochemical and biological factors influencing absorption. Transport across biological membranes. Passive diffusion and Fick’s first law. Partition coefficient. Transport of weak electrolytes and pH-partition theory. Active transport. Other types of transport: facilitated, convective, ion-pair transport.
Principles of Pharmacokinetics. Definitions and main pharmacokinetic parameters. Reaction order: zero-order, first-order, pseudo first-order. Half-life. Pharmacokinetic models. Compartmental and non-compartmental pharmacokinetic analysis. Compartmental models with and without absorption. Residual method. Non-compartmental model: trapezoidal method. Apparent volume of distribution. AUC. Bioavailability: definition. Absolute and relative bioavailability. Calculation examples. Bioavailability with multiple dosing. Bioavailability from urinary excretion curves (overview). Clearance. Bioequivalence.
STABILITY AND STABILIZATION OF MEDICINAL PRODUCTS. Definition and criteria. Chemical, physical, and microbiological stability. Physical degradation. Chemical degradation: hydrolysis, oxidation, photochemical degradation, isomerization. Microbiological stability; zero-order and first-order degradation kinetics. Temperature dependence and Arrhenius theory. Stability studies: stress testing of active ingredients, accelerated stability studies, effect of pH on degradation of active substances.
PRINCIPLES OF PREFORMULATION. Objectives of preformulation studies. Principles and fields of application. Solutions, solubility, and dissolution. Factors affecting drug solubility. The dissolution process. Noyes-Whitney equation. Influence of pH on dissolution rate and salt formation. Other parameters influencing dissolution. Solid-state properties: specific surface area. Polymorphism: unit cells; crystal habit; polymorphism and amorphism; pseudopolymorphism and solvates; polymorphism and bioavailability, examples.
PHARMACEUTICAL POWDERS. Definitions. Fundamental and derived properties. Dimensional classification of powders. Shape factors. Particle size. Statistical mean diameters and size distributions. Particle size measurement methods: sieving, sedimentation and Stokes’ law, Andreasen pipette; granulometric curves; laser light scattering, microscopy (overview). Volume and density of powders: definitions. True density and apparent density; bulk density and tapped density; measurement techniques. Apparent volume. Measurement of surface area. Powder settling and packing. Flowability and angle of repose. Carr’s index or compressibility index. Hausner ratio. Powder mixing and segregation: principles.
INTERFACIAL PHENOMENA. Surface tension and interfacial tension; definitions, principles, measurement methods. Cohesion and adhesion energies. Spreading. Wettability of solid surfaces: contact angle, critical surface tension, wetting coefficient.
DISPERSIONS. Definitions. Thermodynamics of dispersions. Lyophilic and lyophobic colloids. Kinetic properties of colloidal systems: Brownian motion, diffusion, sedimentation, and creaming. Electrical properties of interfaces. Interfacial potentials. Total interaction energy: Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Stabilization of colloidal systems: ionic, steric. Surface-active agents: surfactants. Classification and hydrophilic-lipophilic balance (HLB). HLB calculation. Cosurfactants. Association colloids: ionic and non-ionic micelles, CMC, critical packing parameter. Emulsions: definitions, types. Emulsion instability. Phase diagrams. Special emulsions: multiple emulsions, microemulsions, nanoemulsions, Pickering emulsions. Suspensions: definitions, characteristics. Instability of suspensions: flotation, sedimentation. Sedimentation volume, degree of flocculation.
POLYMERIC MATERIALS. Definitions, nomenclature, and classification; copolymers, polyelectrolytes; structure of polymers and copolymers: linear, branched, crosslinked polymers; number-average and weight-average molecular weights; molecular weight distributions, polydispersity index. Solid-state properties: polymer tacticity; amorphism, semicrystallinity. Natural polymers: polysaccharides and main proteins. Properties in solution: viscosity. Hydrogels. Polymeric materials of pharmaceutical interest (overview).
PRINCIPLES OF RHEOLOGY. Newtonian and non-Newtonian fluids; dilatant, pseudoplastic, thixotropic fluids; dilute and concentrated polymer solutions: viscoelasticity. Flow curves, mechanical spectra.
STERILIZATION. Definition; sterility assurance level (SAL); sterilization time and decimal reduction time; microbial destruction rate, Z-value; sterilization by dry heat: direct flame, hot air ovens; sterilization by moist heat: autoclave; sterilization by UV radiation, ionizing radiation, ethylene oxide.
LYOPHILIZATION. Pre-freezing. Freezing rate and type of lyophil obtained. Eutectic point. Vacuum drying. States of water. Heat of sublimation: Clapeyron equation. Sample heating. Operating pressure. Removal of water vapor: chemical fixation, cold condensers. Final drying. Measuring instruments. Vacuum and temperature. Static and dynamic freezing. Advantages and disadvantages of separate pre-freezer and autoclave pre-freezing. Layer pre-freezing. Control charts. Residual moisture. Final treatment.
Prerequisites
Indispensable: knowledge of General and Inorganic Chemistry and Organic Chemistry
Important: knowledge of the basic concepts of Mathematics and Physics.
Books
Caliceti P,. Tecnologia farmaceutica, Casa Editrice Ambrosiana, 2025
Paolo Colombo et al., Principi di tecnologia farmaceutica, Seconda edizione | Casa Editrice Ambrosiana. Distribuzione esclusiva Zanichelli, 2015
Aulton. Tecnologie farmaceutiche. Progettazione e allestimento dei medicinali, Aulton & Taylor, Edra, 2015
Teaching slides provided by the teacher
Frequency
Attendance of frontal lessons is optional but strongly recommended.
Exam mode
The student evaluation method consists of an oral exam (five examination sessions/year plus 1-2 extra sessions for graduating or off-course students)
The elements taken into consideration for the assessment are: knowledge of the subject
in all the parts described in the exam program, use of an appropriate scientific language,
the ability of reasoning during the oral exam, and the ability to study independently on the texts indicated.
Sufficient knowledge of the topics covered, in the various parts of the exam program, is
required to pass the exam with minimum score (18/30). To achieve a score of 30/30 cum
laude, the student must instead demonstrate that he/she has acquired an excellent
knowledge of all the topics covered during the course, being able to connect them in a logical
and consistent manner.
Lesson mode
The course consists of classroom lectures. Attendance to the lessons is optional but strongly recommended.
