|
|
|
||
|
Subject Physical Principles of Dosage Forms is taught in the third year of study and builds on Biophysics and Physical Chemistry. The aim of the subject is to provide comprehensive information on the basic physical principles used in formulating and stabilizing pharmaceutical forms. In particular, it describes the properties of the solid phase (active compounds and Excipients), liquid phase and dispersion (molecular, colloidal and macrodispersion) and interfacial phenomena that are related to the physical and chemical stability of pharmaceutical products. In the subject of the Physical Principles of Dosage Forms, students will also be acquainted with the basics of polymer chemistry necessary to understand the structure, properties and function of these substances in pharmaceutical formulations and modern drug delivery systems. The basic principles of pharmaceutical nanotechnologies will also be included.<br>
Considering that the physical properties of materials and physical processes at the interface significantly affect the resulting quality of pharmaceutical formulations, understanding these principles is essential for further study of pharmaceutical technology and dosage forms. From this perspective, the Physical Principles of Dosage Forms can be viewed as an interdisciplinary subject with a linking function between fundamental subjects taught in the first section of study and highly specialized pharmaceutical technology.<br>
Topics: Solution properties, Solid-phase, Solid-phase properties, Solubility and dissolution, Diffusion, Interfacial phenomena in pharmaceutical Systems, Pharmaceutical surfactants, Pharmaceutical polymers, Polymer systems, Rheology, Dispersion systems and their stability, Nanotechnology.
Last update: Paraskevopoulos Georgios, doc. Dr., Ph.D. (26.09.2025)
|
|
||
|
Written test Last update: Paraskevopoulos Georgios, doc. Dr., Ph.D. (26.09.2025)
|
|
||
|
Obligatory:
Last update: Paraskevopoulos Georgios, doc. Dr., Ph.D. (26.09.2025)
|
|
||
|
Diffusion Fick's laws Permeation through polymeric membranes Aspects of diffusion within biological systems
Solubility of gases, liquids and solids Dissolution and factors affecting it Drug ionization Dialysis and drug release Solvents for solutions and other systems
Solutions colligative properties
Properties of solids Crystallography Polymorfy Crystal hydrates Surface properties of solid phase Wettability of solid particles Interparticular interactions
Interfacial phenomena liquid/liquid interphase, interfacial tension, factors affecting it Liquid/gas interphase, surface tension, factors affecting it
Surface activity of compounds, surfactants Structural types of surfactants Reduction of surface and interfacial tension HLB system Solubilization Micelles formulation, structural types of micelles, CMC
Disperse systems Types of colloidal systems Stability of colloidal systems
Pharmaceutical polymers Polymeric systems structure, solubility, biodegradability Gels Application of polymers for pharmaceutical preparations Stimuli-responsive polymers
Basics of pharmaceutical nanotechnology Last update: Paraskevopoulos Georgios, doc. Dr., Ph.D. (26.09.2025)
|
|
||
|
Learning Outcomes for the subject Physical Principles of Dosage Forms (GAF308) Solid Phase Define the term phase and component, explain the difference with examples. Explain the difference between intramolecular and intermolecular interactions and list the representatives of these interactions. Explain the difference between covalent and non-covalent interactions. Describe the nature of each intermolecular interaction. Explain what the Lennard-Jones potentials represent and describe its graphical representation. List the parameters of the L.-J. potential and explain what they mean. Define the term phase transition and make a classification of transitions based on Ehrenfest classification. Give examples of first and second order phase transitions. Explain how the heat supplied to the system affects the temperature change during a first order transition. Describe what is represented by areas, curves, and points in a schematic one-component phase diagram. Apply Gibbs law of phases to calculate the degrees of freedom of an m-component system with n-phases. Define and correctly use the terms crystal, polymorph, allotrope, cocrystal, solvate, salt, liquid crystal, crystal lattice, unit cell, and isotropy. State the differences between crystalline and amorphous phases in terms of the arrangement of structural particles and physicochemical properties. State the difference between single crystal and polycrystal and true crystal and quasicrystal. Discuss the advantages and disadvantages and reasons for using amorphous or crystalline forms of API in the pharmaceutical industry. Explain the difference between crystal lattice and motif. Describe the difference between a primitive and a centered cell and list the types of centered cells. List 7 crystal systems and give general lattice parameters using one example of a system. Describe the different stages of crystallization. Define the term supersaturation and discuss how supersaturation can be achieved. Provide a reason for the use of controlled crystallisation by inoculation in the pharmaceutical industry. Classify crystals based on the interactions of the particles. Discuss the implications of polymorphism in terms of physicochemical properties and technological processing. Describe the generation of braking and characteristic X-rays and show schematically the dependence of X-ray intensity on wavelength. Describe the Compton effect, the photoeffect, the formation of Auger electrons, and X-ray diffraction. State the Bragg equation and describe each quantity. Explain the difference between X-ray diffraction of single crystals and X-ray diffraction of powders in terms of the sample material and the information obtained about the sample. Illustrate schematically and describe the function of a powder diffractometer with a Bragg-Brentano arrangement. List the types of X-ray detectors and describe the function of a scintillation detector with a photomultiplier tube. Describe what the intensity, position and profile of the diffraction peaks indicate. Describe the principles of thermogravimetry and differential scanning calorimetry. Explain the difference between exothermic and endothermic phenomena, give examples and schematically illustrate a DSC recording of the heating of an amorphous substance. Summarize the purposes for which thermal analysis can be used in pharmacy.
Surface Properties of the Solid Phase Define and correctly use the terms interface, surface, surface energy, surface tension, porosity, adsorption, adsorbate, adsorbent, desorption, sorption, surface coverage, adsorption isotherm, and water activity. Give a reason for the existence of surface energy. State the equations and units for surface energy and tension and describe each quantity. Describe capillary phenomena and explain the reasons for their occurrence. State the Young-Laplace equation and describe each quantity. State what the Kelvin, Gibbs-Freundlich-Ostwald, Young, and Washburn equations and the Curie-Wulff theorem express. Define for what contact angles a surface is wetted or unwetted by a liquid. List the methods used to characterize the wettability of solid surfaces. Explain the term contact angle hysteresis. Describe the principle of the sessile drop method, Washburn method, Wilhelmy method, mercury porosimetry, gas pycnometry, determination of sorption-desorption isotherm, determination of water activity, and determination of specific surface area by air permeation. Explain the difference between true density, particle density, and bulk density. Explain the reason for the existence of adsorption. State the difference between physical and chemical adsorption. State what isotherms can be used to describe single-layer and multilayer adsorption. Describe what information can be obtained by measuring the BET isotherm.
Dissolution and Solubilization Define and correctly use the terms solution, solvation, solubility, hydrophilic-lipophilic equilibrium, cosolvent, hydrotrope, minimum hydrotropic concentration, critical micellar concentration, and maximum additive concentration. Classify solutions in terms of state, saturation, and dissociation in solvent. Explain thermal phenomena during dissolution. Describe the classification of drugs on the basis of solubility according to the Czech Pharmacopoeia and the biopharmaceutical classification system and evaluate the advantages and disadvantages. Discuss the factors affecting solubility. State Henry's law and describe the quantities. State the Noyes-Whitney equation, describe the quantities, and discuss how the rate of dissolution can be influenced based on this equation. Discuss the differences between the Hildebrand and Hansen solubility parameters. Describe the determination of true and apparent dissolution. Define the 4 classes of drugs according to the Biopharmaceutical Classification System. State Lipinski's rule of five. Justify the efforts to increase the solubility of poorly soluble drugs. List the methods of increasing solubility by chemical and physical modification of drugs. Describe the principle of increasing solubility by increasing wettability, micellar solubilization, use of cosolvent, hydrotrope, pH modifier, formation of complexes, solid dispersions, microgranules, and lipophilic forms. Give examples of excipients used to increase solubility. Describe the structure of liposomes and micelles and discuss the incorporation of hydrophilic and hydrophobic substances. State the differences between micelle-forming surfactants and hydrotropes.
Solutions Define and correctly use the terms solvent, solute, true solution, colloidal solution, ideal solution, real solution, additive properties, constitutive properties, colligative properties, molarity, molality, mole fraction, volume percentage, mass percentage, osmotic pressure, oncotic pressure, osmolality, and tonicity. Classify solutions based on their phase state and particle size and provide relevant examples. Explain the differences between electrolytic and non-electrolytic solutions. Explain various expressions of solution concentration. Discuss the differences between ideal and real solutions including their behavior as described by Raoult’s and Henry’s laws. Explain the differences between cohesive and adhesive interactions in solutions and discuss their significance in relation to solution ideality. Discuss the positive and negative deviations from Raoult’s law. Explain the differentiation between additive, constitutive, and colligative properties of solutions. Explain the the differences in colligative properties between solutions and pure solvents. Explain the osmotic pressure and the phenomenon of osmosis. Define and correctly use the terms osmolarity, osmolality, and tonicity. Comment Van’t Hoff’s correction factor and osmotic coefficient.
Diffusion Define and correctly use the terms of diffusion, diffusion coefficient, diffusion gradient, concentration gradient, membrane, diffusion barrier, steady-state diffusion, membrane resistance, membrane permeability, and semipermeable membrane. Explain the differences between diffusion and Brownian motion and describe the thermodynamic basis of diffusion. Discuss the different diffusion gradients and their pharmaceutical significance. Explain how diffusion differs between different phase states. Describe Fick’s first law and Fick’s second law and discuss their differences. Explain steady-state diffusion and its significance for predicting drug release behavior. Explain the concept of lag-time. Describe membrane diffusion principles and describe the relationship between membrane permeability and resistance. Describe different pharmaceutical processes and their relevance with diffusion including drug release from matrix formulations, osmosis, ultrafiltration, dialysis, hemodialysis, lyophilization.
Rheology Define and correctly use the terms shear stress, velocity gradient, dynamic viscosity, kinematic viscosity, ideal viscosity, and apparent viscosity. and state the units of these quantities. Indicate the subject of interest in rheology and applications in pharmaceutical technology. Characterize Newtonian systems, present Newton's model/law, flow and viscosity curves. Characterize non-Newtonian systems and classify them according to the time dependence of viscosity and flow curves. State the power model and the use of its parameters for characterization of pharmaceuticals. Explain the concept of thixotropy, describe the flow and viscosity curves of thixotropic systems. State the advantages of this behavior for pharmaceuticals. Describe the procedure for measuring viscosity with capillary viscometers. State what the measurement results in and how the kinematic and dynamic viscosity values are obtained. Explain the difference between a viscometer and a rheometer and between a relative and an absolute viscometer/rheometer. State how a spindle suitable for measuring the viscosity of a given sample is selected. State the types of geometries that are used in absolute rheometer measurements. Compare the advantages and disadvantages of a relative viscometer and an absolute rheometer. Explain the concept of consistency. Describe the procedure and evaluation of a penetrometry consistency test. Give examples of excipients for which this test is prescribed.
Interfacial Phenomena Define and correctly use the terms surface, interface, surface tension, interfacial tension, free surface energy, positive adsorption, negative adsorption. Describe surface tension, including the role of cohesive interactions at the surface versus the bulk phase. Describe free surface energy, the factors influencing it, and its relationship with surface tension. Discuss the significance of surface tension and free surface energy for the stability of pharmaceutical formulations and discuss factors affecting surface tension. Discuss the nature of surface tension at liquid surface and distinguish between surface tension and interfacial tension between liquids. Explain values of surface and interfacial tension across various liquids and the underlying reasons for the different values. Describe the spreading coefficient and the factors on which it depends. Describe and compare the different methods for measuring surface tension such as stalagmometry, capillary methods, and detachment methods. Discuss the principles of adsorption at phase interfaces and explain the terms positive and negative adsorption and their impact on drug delivery systems.
Surfactants Define and correctly use the terms surfactant, amphiphilic compound, solubilizer, emulsifier, detergent, wetting agent, critical micellar concentration (CMC), micelle, hydrophilic-lipophilic balance (HLB), macrogol esters, polysorbates, poloxamers. Describe the nature of surface-active agents and identify the structural characteristics necessary for surface activity. Discuss the classification of surfactants including differentiations based on the structure of the hydrophilic and lipophilic segments. Explain the role of surfactants in pharmaceutical applications, including solubilization, emulsification, and wetting. Explain the HLB system for surfactant classification and compare the calculation of HLB values using Griffin’s and Davies’ methods, assessing their applicability to different types of surfactants. Describe micelles, explain their formation, and evaluate their importance in pharmaceutical formulations. Define the critical micellar concentration (CMC) and describe the physicochemical changes that occur as surfactant concentration increases. Describe different ionic and nonionic surfactants together with their characteristics and relevant examples with their HLB values. Discuss the emulsion formulation and the role of HLB values in emulsion type and stability. Describe surfactant applications in pharmaceutical suspensions and their role in stabilizing dispersed systems. Explain the function of wetting agents and describe their significance in formulation science.
Polymers 1 and 2 Define and correctly use the terms macromolecule, monomer, oligomer, polymer, linear polymer, branched polymer, homopolymer, heteropolymer, copolymer, block copolymer, grafted copolymer, atactic polymer, isotactic polymer, and symmetric polymer. Describe the differences between addition and condensation polymerization methods and discuss the conversion degree over the process of the two methods. Describe the methods for the polymer molecular weight determination, including laser diffraction, viscometry, chemical analysis, gel chromatography, MALDI-TOF, and elemental analysis of copolymers. Discuss the distinction between number-average and weight-average molecular weights. Define polymer polydispersity, discuss its possible values, and explain how it influences polymer properties. Discuss the concept of polymer crystallinity and explain how it is affecting the polymer properties. Describe the polymer glass transition temperature and analyze the factors influencing it. Discuss how polymer structure impacts glass transition temperature. Discuss the applications of polymers in pharmaceutical sciences. Describe polymer swelling and dissolution, distinguishing between polymer solutions and gels. Describe stimuli-responsive polymers and discuss their potential applications in pharmaceutical formulations.
Dispersed Systems Define and correctly use the terms dispersed system, continuous phase, dispersed phase, colloidal dispersion, coarse dispersion, lyophilic colloid, lyophobic colloid, association colloid, suspension, emulsion, zeta potential, electrical double layer, Nernst potential, Stern potential, DLVO theory, and controlled flocculation. Classify dispersed systems based on particle size and describe the key differences between various types. Describe colloidal dispersions and their stability and analyze how electrolytes influence their behavior. Describe the electrical double layer at phase interfaces and explaining the principles of Nernst potential and zeta potential. Discuss the role of these potentials in the stability of dispersed systems. Classify the different types of instability in dispersed systems and propose appropriate stabilization strategies. Explain the concept of controlled flocculation, its objectives, and the necessary parameters and excipients required to achieve controlled flocculation. Discuss the advantages of flocculated suspensions and the risks associated with deflocculated suspensions.
Nanotechnology Define and correctly use the terms nanomaterial, nanoparticle, and nanopharmaceuticals. Describe the rationale of nanoparticles for drug delivery and distinguish between pharmacokinetics and particokinetics. Discuss the different parts of nanoparticles and explain the importance of particle size for the properties of nanoparticles. Discuss the physicochemical characterization of nanoparticles in relation to their use and in relation to preparation and properties. Describe different methods for the preparation of nanoparticles together with the key steps of each procedure. Describe the structure of dendrimers and their differences from the classical polymers.
Last update: Paraskevopoulos Georgios, doc. Dr., Ph.D. (26.09.2025)
|