Objectives

General expected learning outcomes
The teaching of Applied Pharmaceutical Chemistry regards the study of the mechanisms of organic reactions involved in drug metabolism and related to the planning and action of drugs. Pre-formulation studies and accelerated storage tests are introduced in order to calculate the shelf-life of the formulations. Industrial methods to separate, sterilize and freeze-dry an active molecule are also studied.

Specific expected learning outcomes
1. Knowledge and understanding
The student will able to know and understand metabolic processes that drugs understand, valuing the problems of a specific drug, such as toxicity of itself and of its metabolites, as well as any problems of bioavailability and/or stability. The student will acquire knowledge about industrial processes such as filtration, sterilization and freeze-drying.

2. Applying knowledge and understanding
The student will be able to value the problems of a drug and to plane pharmaceutical formulations that allow of overcoming these problems, through chemical modifications of the active. The student will be able to determine the stability of the formulation and to value the deadline of the medicine. Starting to the knowledge of the industrial processes of sterilization, filtration and freeze-drying will be able to choose the best methodologies to apply at a specific drug.

3. Making judgements
The lessons will be interactive, with a continue comparison between teacher and students about the arguments with the aim to stimulate the interest of the students and to increase their critical sense. This discussion will allow calling back arguments already discussed in other teachings, and connected among them.

4. Communication skills
The rating of the student will be made through an oral examination that will have as subject one of the arguments treated during the lessons and applied to a specific drug and this will allow of valuing the making to correlate different aspects and to explain them with adequate scientific language.

5. Learning skills
The student will be able to search in the literature and to study critically the scientific papers related to the teaching. In this way, he will be able to elaborate the possible problems related to the drugs and to overcome them as requested by the industrial world.

Channels

NESSUNA CANALIZZAZIONE

MARIA ANTONIETTA CASADEI MARIA ANTONIETTA CASADEI   Teacher profile

Programme


CHAPTER 1. DRUG METABOLISM
1.1. ENZYMES AND COENZYMES IN DRUG METABOLISM (8 hours)
Introduction. Mechanisms of enzyme catalysis. Coenzyme catalysis. Pyridoxal 5’-phosphate (PLP): reactions catalyzed by PLP-dependent enzymes. Mechanism and Dunathan hypothesis. Racemases, decarboxylases, aminotransferases, B-elimination. Tetrahydrofolate: reactions catalyzed by tetrahydrofolate -dependent enzymes. Mechanism of carbon unit transfer. Flavins: reactions catalyzed by flavin-dependent enzymes. Mechanisms of regeneration of the oxidized coenzymes. Heme: reactions catalyzed by heme-dependent enzymes. Activation of the coenzyme and reactions of hydroxylation and epoxidation. Adenosine triphosphate (ATP) and coenzyme A (CoA): reactions and mechanisms.
1.2. PHASE I TRANSFORMATIONS (10 hours)
Introduction. Analytical methods in drug metabolism. Synthesis of radioactive compounds.
Oxidative reactions. Enzymatic involved systems. Aliphatic and aromatic hydroxylation.Alkene epoxidation. Oxidations of carbons adjacent to sp2 center. Oxidations of carbon-nitrogen, carbon-oxygen, carbon-sulfur systems. Other oxidative reactions.
Reductive reactions. Introduction. Carbonyl, nitro and azo reduction. Reductive dehalogenation.
Hydrolytic reactions.
1.3. CONJUGATION REACTIONS (6 hours)
Introduction. Reactions of glucuronic acid, sulphate, methyl, acetyl conjugation. Mechanisms and involved substrates. Conjugation reactions that involved CoA. Reactions of conjugation and redox with glutathione. Other conjugation reactions.
1.4. DRUG METABOLISM AND PHARMACEUTICAL SYNTHESIS (2 hours)
Structural modifications to modulate drug metabolism. Hard and soft drugs.
CHAPTER 2. PRODUGS (10 hours)
Utility of prodrugs. Types of prodrugs.
2.1. MECHANISMS OF ACTIVATION
Carrier-linked prodrugs. Carrier-linkages for various functional groups.
Examples of carrier-linked bipartite prodrugs. Prodrugs for increase water solubility, for improved absorption and distribution, for site specificity, for stability, slow and prolonged release, for minimize toxicity, to encourage patient acceptance, to eliminate formulation problems.
Macromolecular drug carrier systems. General strategy. Synthetic polymers. Poli-aminoacids. Other macromolecular supports.
Tripartate prodrugs.
Mutual prodrugs.
Bioprecursor prodrugs: origins. Oxidative activation. N- and O-dealkylations, oxidative deamination, N-oxidation, other oxidations. Reductive activation: azo, azido, sulfoxide, disulfide, nitro reduction. Nucleotide, phosphorylation, sulfatation, decarboxylation activation.
CHAPTER 3. DRUG STABILITY (6 hours)
Introduction. Chemical and physical decomposition. Kinetics of chemical decomposition in solution. Order of reaction. Determination of the order of reactions. Complex reactions. Kinetics of chemical decomposition in solid dosage forms.
Stability testing and prediction of shelf-life. Effect of temperature on stability. Protocol for stability testing.
CHAPTER 4. POLYMERS AND MACROMOLECULES (6 hours)
Pharmaceutical polymers. Definitions. Polydispersity. Solubility.Water-soluble polymers. General properties of polymer solutions. Viscosity. Gelling water-soluble polymers. Polymer complexes. Binding of ions to macromolecules. Some water-soluble polymers used in pharmacy and medicine. Carboxypolymethylene, cellulose, dextran.
Water-insoluble polymers and polymer membranes. Some applications of polymeric systems in drug delivery. Matrices. Microcapsules and microspheres.
CHAPTER 5. FUNDAMENTAL PROCESSES IN PHARMACEUTICAL INDUSTRY
5.1. FILTRATION (4 hours)
Introduction. Objectives. Types of materials to be filtered. Theory. Equations of Poiseuille, Darcy, Kozeny. Types of filters. Materials employed in filtration. Gravity filters. Rotative filter. Oliver filter. Pressure filters.
5.2 STERILIZATION (6 hours)
Physical means. Heat sterilization. Dry heat sterilization .Flame system. Equipment to air dry. Moist heat sterilization. Flowing steam, saturated steam under pressure. Advantages of the use of steam. Autoclaves. UV rays. Gamma rays. Beta rays. Advantages and disadvantages. Other physical methods: ultrasound, x-ray sterilization. Parameters for the evaluation of sterilization processes: D value, Z value, factor inactivation. Bactericides, disinfectants. Gas sterilization: ethylene oxide, beta - propiolactone. Mechanical methods: filtration. Filter Berkefeld, Chamberland and Selas, Seitz filters, Pal cartridges. Glass filters. Membrane filters. Aseptic preparation. Air treatment. Laminar flow hoods.
5.3 FREEZE-DRYING (6 hours)
Freezing rate and type of lyophilized obtained. Noyes -Whitney equation. Eutectic point. Drying under vacuum. State of aggregation of water. Heat of sublimation: Clapeyron equation. Heating of the sample. Vacuum pumps. Rotary pumps. Use of gas - ballast. Rotary pumps at one and two stages. Rotary piston pumps. Roots pumps. Elimination of water vapor chemical fixation, capacitors cold. Law Knudsen. Refrigerant mixtures. Final drying. Measuring equipment. Vacuum and temperature. Static and dynamic freezing. Pre-cooling in layers. Control cards. Residual moisture. Final treatment.

Adopted texts

1) R. B. Silverman "The Organic Chemistry of Drug Design and Drug Action" Academic Press, 2a edizione, 2004.
2) "Burger's Medicinal Chemistry and Drug Discovery" - 5a edizione, Volume I-M. E. Wolff editore - J. Wiley, 1995
3) G. S. Banker - C. T. Rhodes "Modern Pharmaceutics" 3a edizione- M. Dekker, 1996.

Prerequisites

Essential preconditions: Organic Chemistry, Biochemistry Important: Physiology, Pharmacology and Toxicology Useful: Inorganic Chemistry, Drug analyses, Food Chemistry.

Study modes

The teaching of Applied Pharmaceutical Chemistry consists of frontal lessons and one or two seminars. The lessons are interactive. The teacher tries to stimulate the students, highlighting the contact points among the different teachings, in order to give a full and homogeneous vision of the degree course. The multidisciplinary is a characteristic of the graduate in Drug Chemistry and Technology that makes him suitable for different jobs in the pharmaceutical world. The students get the teaching materials necessary for the study during the first lesson (program, books…). The teacher during the frontal lessons presents the arguments and practical examples of drugs formulations. The frequency of the lessons is not mandatory but is recommended.

Exam modes

At the end of the teaching, the student has to pass an oral examination. Eight exam appeals are fixed on Infostud in one year; one of each is opened for ten days, so that students can avoid overlaps with other examinations of the same period. The students that do not pass the examination can recur it during the following appeal. The time of the exam is variable. If the student is able to range over the arguments of the program, and to carry out connections among the different aspects of the proposed subject the examination time can be of about half an hour. Otherwise, more than one hour can be necessary to help the student to have a full vision of the drug problems. The aim of the test is to verify the knowledge and understanding of the students about drug problems and the modifications that is possible to introduce on the molecule in order to overcome them. The students have to communicate their knowledge clearly and with adequate language.
The valuation elements are: knowledge of the subjects, suitable language, involvement at the lessons, ability to connect the arguments of the teaching to the already studied ones, ability to solve a specific problem related to the formulation of a specific drug, ability to study autonomously.
A sufficient knowledge of the arguments is required to pass the examination with the minimum mark. To obtain the maximum mark, the student has to show a very good knowledge of all the arguments and to be able to present them logically and with suitable scientific language.
A sufficient knowledge of the arguments is required to pass the examination with the minimum mark. To obtain the maximum mark, the student has to show a very good knowledge of all the arguments and to be able to reply to the required questions clearly and with suitable scientific language.

Exam reservation date start Exam reservation date end Exam date
02/01/2022 16/01/2022 18/01/2022
01/02/2022 13/02/2022 15/02/2022
01/04/2022 11/04/2022 13/04/2022
28/05/2022 08/06/2022 10/06/2022
20/06/2022 02/07/2022 04/07/2022
08/09/2022 17/09/2022 20/09/2022
10/10/2022 23/10/2022 25/10/2022
12/11/2022 27/11/2022 29/11/2022
02/01/2023 18/01/2023 20/01/2023
Course sheet
  • Academic year: 2021/2022
  • Curriculum: Curriculum unico
  • Year: Fourth year
  • Semester: First semester
  • SSD: CHIM/09
  • CFU: 8
Activities
  • Attività formative caratterizzanti
  • Ambito disciplinare: Discipline Chimiche, Farmaceutiche e Tecnologiche
  • Lecture (Hours): 64
  • CFU: 8
  • SSD: CHIM/09