Objectives

The course aims to provide the student with basics in formulation of biotechnological drugs, as well as, development of conventional and innovative pharmaceutical dosage forms. To this end, the course aims to give adequate theoretical bases in order to make the student able to comprehend the relation between the properties of the different dosage forms and their biopharmaceutical and pharmacokinetic fate in vivo, considering the physico-chemical properties of the drug as well as the therapeutic objective. At the same time, the course aims to provide deep knowledge on different formulation strategies and analytical techniques to characterize the pharmaceutical forms.
The course further aims to provide the student with knowledge about manufacturing, registration and commercialization of biotechnological drugs. Overall, the course aims to develop knowledge about the main formulation, manufacturing, quality and regulatory issues.
At the end of the course, the student should demonstrate:
1) Knowledge and understanding skills on the following topics:
- basics on formulation, manufacturing and quality control of the principal conventional and innovative dosage forms;
- technological characteristics of the excipients;
- theoretical bases of controlled release of drugs;
- pharmaceutical legislation and regulation with focus on biotechnological drugs.

2) Applying knowledge and understanding
The course aims to provide the student with general principles to optimize the efficacy of biotechnological drugs, taking into consideration the physico-chemical and stability properties of the active molecule as well as the administration route, the delivery vehicle and the targeting strategy more suitable to achieve the desired therapeutic effect. Therefore, the student will be able to follow the steps of the manufacturing process of medicines and to prepare the principal conventional and innovative dosage forms, taking into account potential formulation, regulatory and safety issues.
3) Making judgements
At the end of the course, the student will write a report to demonstrate its ability to evaluate the technological, regulatory and safety issues related to the manufacturing of a conventional or innovative dosage form.
4) Communication skills
During the course, some roundtables sessions will be carried forward under the direction of the professor to evaluate the communication skills of the student. These sessions will be important to develop the ability to critically evaluate technological, regulatory and safety issues related to the manufacturing of conventional or innovative dosage forms. They will also be useful to develop the ability to properly report this information to both expert and inexpert persons.

5) Lifelong learning skills
The course will provide the student with theoretical basis and tools to develop independent lifelong learning skills, in order to make it able to further enrich its knowledge, thus maintaining it on a constant level. This point is particularly important considering the quick and incessant evolution of the pharmaceutical technologies and legislation.

Channels

NESSUNA CANALIZZAZIONE

PATRIZIA PAOLICELLI PATRIZIA PAOLICELLI   Teacher profile

Programme

Topic 1 (9 hours). Design of pharmaceutical dosage forms. Biopharmaceutical aspects of pharmaceutical dosage forms. Therapeutic considerations in the design of pharmaceutical dosage forms. Routes of drug administration. Drug-related considerations in the design of pharmaceutical dosage forms. Therapeutic considerations in the design of pharmaceutical dosage forms. Therapeutic effect and bioavailability (absolute and relative) of drugs. Factors related to the drug and dosage form that affect bioavailability. Pharmacokinetics and pharmacodynamics. Absorption, distribution and elimination of drugs. Barriers to drug absorption. Pharmacokinetic parameters and their determination. Dosage regimen design. Influence on the plasma concentration-time profile of a drug in the body. Main factors influencing the plasma concentration of a drug. Dose and frequency of drug administration. Loading-dose concept. The Pharmacopoeias and their role for the quality of medicines. The Good Manufacturing Practice. Production and control of medicinal products. The concept of quality in the pharmaceutical industry from development to production. The pharmaceutical quality system. Pharmaceutical development: preformulation. Physical and chemical properties of the drug. Solubility. Dissolution. Partition coefficient. Dissociation constant. Stability of biotechnological drugs. Physical and chemical stability. Reactions of degradation in solution and in solid state.

Topic 2 (16 hours). Pharmaceutical development: pharmaceutical formulation. Components of the pharmaceutical preparation. Active ingredients and compatibility. Chemical-physical characteristics of the drugs. Excipients and not active components. Choice of excipients. Quality and quantity of the excipients. Pharmaceutical forms: classification according to the route of administration and classification according to the release rate. Conventional and innovative pharmaceutical forms. Water for pharmaceutical use. Water quality and water classification for pharmaceutical use. Water characteristics for pharmaceutical use and production technologies. Purified water, highly purified water and water for injection. Water treatments and conditioning. Dechlorination, demineralization, ion exchange resins, reverse osmosis, distillation (single and multiple-effect distillation).

Topic 3 (16 hours). Liquid pharmaceutical preparations. Solutions. Properties of solutions and their preparation. Advantages and disadvantages of pharmaceutical solutions. Solution stability. Isotonic pharmaceutical forms. Concepts of isotonicity. Methods for adjusting tonicity. Dispersed systems: colloidal systems. Electrical properties at interphase. Stability of colloids. Pharmaceutical applications. Suspensions. Particle wettability. Contact angle. Interactions between solid particles and liquid vehicle. Electric double layer theory and factors that influence it. DLVO theory. Diffusion and sedimentation. Free surface energy. Enlargement of the particles. Flocculation and deflocculation. Ostwald ripening phenomenon. Suspension formulation. Suspension stability. Bioavailability of suspended drugs. Quality control on suspensions. Emulsions. Types of emulsions. Emulsion stability. Surface tension. Surfactants: definition and classification. Definition of HLB. Micelle formation. Preparation of emulsions. Conce of required HLB. Quality controls on emulsions. Evaluation of the stability of emulsions.

Topic 4 (16 hours). Innovative and modified-release pharmaceutical forms. Delayed and controlled release pharmaceutical forms. Active and passive drug targeting. Polymeric materials for the development of modified-release pharmaceutical forms. Definition, classification and characteristics of polymers. Polyesters. Cellulose. Polyurethanes. Polyacrylates. Microparticulate carriers of drugs. Classification and properties of microparticles. Preparation methods and characterization of microparticles. Nanoparticulate carriers of drugs. Classification and properties of nanoparticles. Lipid and polymeric nanoparticles. Methods of preparation of nanoparticles. Methods of characterization of nanoparticles. Overview of light diffusion. Routes of administration, distribution and in vivo fate of the nanoparticles. Therapeutic applications. Vesicular vectors: liposomes. Definition and classification of liposomes. Mechanism of formation of liposomes. Critical packing parameter. Thermotropic phase transitions and their effect on the properties of liposomes. Overview of differential scanning calorimeters. Preparation and characterization of liposomes. Concept of trapped volume and its determination. Stability of liposomes. Routes of administration and therapeutic applications of liposomes. Evolution of liposomes: development of stealth liposomes. Hydrogels. Definition and classification. Properties of physical and chemical hydrogels. Methods of preparation of physical hydrogels. Methods of preparation of chemical hydrogels. Injectable and in-situ gelling polymeric systems. Characterization of hydrogels. Principles of rheology. Newtonian and non-Newtonian fluids. Time-dependent behavior: thixotropy. Viscometers and rheometers. Viscoelasticity. Application of rheology to pharmaceutical formulations. Hydrogel evolution: interpenetrate systems, double-network systems and cryogel systems. Concept of cryogelation and its effect on hydrogel properties.
Topic 5 (16 hours). Sterile and pyrogen-free pharmaceutical forms. Kinetics of microbial inactivation (D and Z value). Sterilization and depyrogenation methods. Sterilization with dry and moist heat. Antimicrobial effects of dry heat and moist heat. Resistance of microorganisms to dry and moist heat and factors that influence it. Use of the autoclave in the sterilization process. Sterilization with ethylene oxide and factors influencing it. Sterilization with other chemical agents. Sterilization by ionizing radiation. Particle and electromagnetic radiation. Effect of ionizing radiation on materials. Factors that influence the resistance of microorganisms to radiation. Sterilization with UV radiation and factors that influence UV resistance. Sterilization by filtration. Effectiveness and limits of sterilization methods. Sterility evaluation test. Validation of a sterilization process. Environments for the production of sterile pharmaceutical forms. Classification of sterile premises. Air sterilization. Cleaning and sterilization of the sterile block. Checking the contaminations of the sterile block. Packaging of medicinal products. Primary and secondary packaging. Packaging materials. Glass. Plastics. Rubbers and elastomers. Metals. Laminates. Drying processes: lyophilization and spray-drying. Definition and properties of freeze-dried products. Stages of the freeze-drying process. Freezing stage. Primary and secondary drying. Use of cryoprotectants and lioprotectors. Quality control of the lyophilization process.
Topic 6 (24 hours). National and supranational institutions. Rules concerning the production and marketing of medicinal products for human use. Biosimilar medicines. Pharmacovigilance. Traceability of medicines. Medical devices.

Adopted texts

1) Aulton ME, Tylor KMG. Tecnologie farmaceutiche. Progettazione e allestimento di medicinali
2) Colombo P et al. Principi di Tecnologia farmaceutica
3) Farmacopee Ufficiali (Current editions)
4) Fabris L, Rigamonti A. La fabbricazione industriale dei medicinali
5) Minghetti P. Legislazione farmaceutica
6) Brusa P, Baratta F. Manuale di Legislazione Farmaceutica
7) Material provioded bi the teacher

Prerequisites

To comprehend the lessons of Pharmaceutical Technology and Legislation it is useful to have acquired knowledge of general chemistry, organic chemistry, biochemistry and applied biochemistry

Exam modes

The competence of the student is assessed through the preparation of a written report on a topic agreed upon with the teacher. The student will have to demonstrate independent learning ability. The work produced by the student will be presented and discussed during the oral examination. The oral exam lasts an average of one hour per student. During this time, the teacher verifies the student's knowledge and reasoning skills on the main conventional and innovative dosage forms and on the regulations concerning the preparation and marketing of medicines. The arguments presented should be treated with an appropriate language.

Exam reservation date start Exam reservation date end Exam date
01/02/2020 19/02/2020 21/02/2020
01/04/2020 13/04/2020 15/04/2020
01/06/2020 28/06/2020 30/06/2020
01/07/2020 25/07/2020 27/07/2020
01/08/2020 13/09/2020 15/09/2020
02/11/2020 14/11/2020 16/11/2020
01/12/2020 12/12/2020 14/12/2020
28/12/2020 16/01/2021 18/01/2021
Course sheet
  • Academic year: 2019/2020
  • Curriculum: Curriculum unico
  • Year: Second year
  • Semester: First semester
  • Parent course:
    1041404 - PHARMACEUTICAL TECHNOLOGIES AND LEGISLATION
  • SSD: CHIM/09
  • CFU: 9
Activities
  • Attività formative caratterizzanti
  • Ambito disciplinare: Discipline farmaceutiche
  • Lecture (Hours): 72
  • CFU: 9.00
  • SSD: CHIM/09