B016598 - APPLIED PHARMACEUTICAL CHEMISTRY

italian

Solid state properties important in drug development. Thermoanalysis, X-ray diffractometry and other techniques for solid state characterization. Diffusion and dissolution of drugs. Biopharmaceutic and pharmacokinetics principles. Preformulation studies. Stability studies. Drug delivery systems with modified- and/or targeted-release for different administration routes. Polymers of pharmaceutical interest. Biotechnologies in preparation, release and targeting of drugs.

PHYSICAL PHARMACY, Martin, Swarbrick, Cammarata, Lea & Febiger Eds., Philadelphia. Chapters 5, 13, 14, 15, 22 (

THE THEORY AND PRACTICE OF INDUSTRIAL PHARMACY, Lachman, Lieberman, Kanic, Lea & Febiger Eds., Philadelphia. Chapters 8, 9, 14

BIOFARMACEUTICA E FARMACOCINETICA, Shargel, Ed. Masson

REMINGTON'S PHARMACEUTICAL SCIENCES. Chapters 16, 18, 36, 75, 81, 91

The aim of this course is the study of the physicochemical properties of the drug and of the excipients presents in the different dosage forms, in order to optimize and tune the drug therapeutic efficacy. The course provides the methodologies and the knowledge necessary to solve the chemical-physical and technological problems to transform the drug in the final dosage form, improve its biopharmaceutical properties, develop the most suitable formulation, modulate the release rate and direct the drug to the target site.

As by the study plan

The course is based on theory lessons, theoretical exercises, and laboratory demonstrations

Files of all the slides of the course are available for the students. Time of reception: all days, by prior appointment

The final examination consists of an oral exam aimed at verify the knowledge of all the topics. Examination dates are indicated on the website of the Degree Course. Online registration is required.

From therapeutic idea to pharmaceutical product: overview of problems connected with the drug development from its discovery up to the medicinal product registration. Solid state properties important for drug development: amorphous and crystalline state: habitus and internal structure (elementary cell, crystalline systems); polymorphism: structural and thermodynamic aspects, enantiotropy and monotropy; pseudo-polymorphism; solid state and relationships with solubility, dissolution and absorption of drugs. Thermoanalytical techniques in the solid state investigation of drugs: Principles of TGA, EGA, DTA, DSC (heat flux and power compensation), HSM and TMA. Applications: characterization of raw materials (fusion, desolvation, polymorphic transitions, decomposition), studies of binary systems, phase diagrams, compatibility studies, stability studies, development of galenic forms, control of finite forms. X-ray diffractometry in drug solid state investigation: X-ray characteristics (Bragg's law); powder method, characterization of amorphous and crystalline substances in quali-quantitative analysis of mixtures. Single crystal analysis. Other methods of solid state investigation: applications of FTIR and NIR spectroscopy.
Diffusion and dissolution of drugs: mass transport through membranes and natural and artificial barriers; diffusion and permeability coefficients; applications of I and II Fick's law; diffusion from solutions, suspensions, matrices, gels or ointments (Higuchi equations). Solubility: determination and factors that influence it. Dissolution rate; kinetic models; laws of Noyes-Whitney and Nernst-Brunner; "Sink conditions", intrinsic dissolution rate (Wood method); Hixson-Crowell equation. Factors related to the drug physico-chemical properties, dosage form and dissolution test parameters influencing the dissolution rate; official (USP, FUI) and not official apparatus for dissolution test. Preformulation studies in drug development: Evaluation and optimization of the drug molecule. Approaches to improve the solubility of poorly water-soluble drugs: a) intervention on the drug molecule; b) changes in drug solid state; c) solid dispersions; d) other methods; e) complexation; complexes with cyclodextrins. Properties of natural and derived cyclodextrins, thermodynamic aspects of the interaction with drugs in aqueous solution and in the solid state; other uses of cyclodextrins
Principles of biopharmaceutics and pharmacokinetics: types of equivalence of pharmaceutical forms; bioequivalence. Absolute and relative bioavailability; biological, chemical-physical and technological factors that can influence it. In vivo and in vitro (simulated absorption tests) evaluation of bioavailability Amidon. BCS classification. Vivo-vitro correlations. Plasma level-time curves. Pharmacokinetic models and parameters. Dose calculation in modified release formulations. Principles of chemical kinetics and drug stability studies: Types of stability and factors influencing. Rate and order of reaction, kinetic equations, half-life and shelf-life. Arrhenius equation, accelerated isothermal and non-isothermal stability tests. Statistics on the estimate of shelf life of solid pharmaceutical forms. Approaches for the stabilization of drugs against the main decomposition reactions. Stability requirements and problems of physical stability of various galenic forms.
Therapeutic systems with modified and/or site-specific release: definitions and terminology. Main mechanisms of drug release control. Methods and approaches for obtaining a modified release. Classification according to the drug release mechanism. Oral solid pharmaceutical forms (reservoir-membrane systems, matrix, ion exchange systems, osmotic systems, prodrug) and parenteral (intramuscular injection, subcutaneous, intravaginal, intrauterine, intraocular, transdermal systems, nasal powders). "Right time" systems. Methods for delaying the gastrointestinal transit. Colonic release. Targeted delivery systems: microparticles, nanoparticles (liposomes, niosomes, polymeric and lipid nanoparticles), monoclonal antibodies, immunotoxins. Biotechnological methods in drug preparation, release and targeting. Polymeric materials of pharmaceutical interest: Average molecular weights and substitution degree; polymer-water interactions; structure, crystallinity degree, glass transition, and mechanical properties (Hooke's law, stress-strain curves) of polymers in the solid state. Polymers in U.S.P. and F.U.I.; applications in the pharmaceutical field.