32046 - Pharmaceutical Technology and Law II

Learning outcomes

After completing the course the student knows the chemical and
physical characteristics of pharmaceutical excipients and methods
of preparation and functional assessment of pharmaceutical
formulations for controlled release and bio-distribution of drugs.
The student will be able to apply their knowledge to the
implementation and evaluation of innovative and conventional
pharmaceutical forms.

Course contents

(attendance at lectures is strongly recommended: from the teaching regulations of the CDS (article 4) the attendance requirement is satisfied with at least a 60% attendance of the lectures and 80% of the laboratory exercises)

Module 1: “PHARMACEUTICAL TECHNOLOGY AND LAW – TECHNOLOGICAL CONTROLS” dr L. Marchitto (3 ECTS)

Advanced technical, controls and quality procedures for medicines formulation: Quality of the raw materials: API’s EDMF (European Drug Master File), COS/CEP. European Pharmacopoeia Monography n°2034 “Substance for Pharmaceutical Use”. Management and risk assessment for organic impurities, genotoxic impurities, residual solvents, elemental impurities. Quality of used excipients.

Dissolution test for a new solid dosage form development. design, test run and data analysis. UE and USA guidelines

Stability studies on medicines (fondamentals)

Pharmaceutical packaging technology: characteristics and used materials, primary packaging, role in the formulation and stability of a medicinal product, "extractable and leachable", secondary packaging, purpose and role of communication to users Stability studies for medicines. (fundamentals)

Pharmaceutical pre-formulation: pre-formulation as part of the development of a medicinal product, objectives of studies, characterization of the active substance: fundamental properties and derived properties, organoleptic characteristics: color, odor, flavor, properties of drugs and excipients in solid form: crystal habit, analysis of the solid state, polymorphism and bioavailability of drugs, partition coefficient oil / water solubility and intrinsic solubility, degree of ionization of an active and salting. Drug /excipients compatibility studies.

Module 2: “BOPHARMACEUTICS - DRUG DELIVERY” Prof. P.Blasi (4 ECTS)

Pharmacokinetic model of the drug disposition in the body related to therapeutic system. Therapeutic systems. Release, absorption, distribution, metabolism and elimination of drugs. Dose and dose bioavailable. AUC. Absolute bioavailability and relative bioavailability. Bioequivalence: chemically equivalent and bioequivalent alternative products. Dosing regimens and blood levels. Loading doses and maintenance doses. Dosing regimens ideal. Control of plasma by formulation variables. Biopharmaceutical aspects in pharmaceutical systems for immediate release or modified release. Pharmaceutical forms and nano-particulate. Passive targeting, active and physical. Polymeric nanoparticles, solid lipid nanoparticles, dendrimers, liposomes, macromolecular systems and self-assembling. polymers. Systems for the gene-delivery. Chemical and physical characteristics of the drug-carrier systems, preparative technologies and functional characteristics.

MODULE 3 : “FORMULATION AND PHARMACEUTICAL DEVELOPMENT- DRUG TARGETING ” - dr. Leonardo Marchitto (3 ECTS)

Technical regulation for drug development and regulatory affairs: basic definitions, European guidelines for medicine development and registration. European Medicines Agency (EMA), European and Italian legislation for a medicinal product. Marketing Authorisation procedures, procedures for registration a medicinal product, “variation” and Italian Drug Agency (AIFA), authorization for production, Common Technical Document (CTD / Dossier): content, activities for development a new medicinal product.

Medicinal product, strategies and development pathways for: “generics product”, “medicine whit modified formula or administration“; “new API- new medicinal product” . EMA/ICH guidelines for formulation and registration a medicinal product: ICH «Q8A- Pharmaceutical Development» guideline. EMA/ICH guideline for a new medicinal product specification definition (fundamental)

Advanced Formulation Technologies and development for liquid and semi-solid pharmaceutical forms: Industrial development and validation of oral liquid and semi-solid dosage forms. Choice of surfactant system and wetting agent, choice of antimicrobic and antioxidant system, choice of viscosity agent. Dispensing of oral drops and oral liquid dosage forms: droppers and other dispensing devices for liquid. Microemulsions: characteristics, use, formulation and development. Nanosuspension: characteristics, use, formulation and development.

Transdermal Systems, iontophoresis, sonophoresis, micro-needle, Jet Injection (needle free injection)

Muco-adhesive formulations: oro-mucosal, ophthalmic, nasal, vaginal.

Advanced Formulation Technologies and development for Areosols and inhalation dosage forms: anatomy and physiology of respiratory tract, inhalatory biopharmaceutics, inhalation technology and nebulization; pressurized Metered Dose Inhaler (pMDI) formulation, production and controls; Dry Powder Inhalers (DPI): formulation, production and controls. Dispensing inhalation dosage form. Use of spacer for children and adult people.

Advanced Pharmaceutical Technologies for solid oral dosage forms development: Industrial development and validation of solid dosage forms, pellets and pellet production. Scored tablets, formulation approach, “Breakability

test”. The “Snaps-Tabs” and tablet-splitter”, pharmaeconomics /therapeutics needs for tablet scoring. Dispensing scored tablets. Fast release: ODT, Oro-dispersible granules and tablets, ODF: Oro-dispersible film-strip, "Taste Masking" technologies.

Solid dosage forms and modified release: delayed -release, sustained release and targeting.

Formulation and pharmaceutical development of medicines for paediatric use: guideline

Module 4: Laboratory - Dr. Antonio Mazzucco (2 ETCS)

1: Preparing a mucilage base

Preparation of a wet granulate; using granulator

Preparing oleogel and hydrogel

Uniformity of weight of tablets

2: Dimensional analysis using sieves, vibrating screen

Measuring angle of repose of a granular material

Prepare a paste and demonstration of the Refiner

emulgel preparing

3: Measurement of the density of a powder with a hydrometer

Monsanto hardness tester; Friabilometer; De-aggregator

Preparation of an emulsion and analysis using Microscope

Suppositories with the method of the double fusion

Ointment preparation.

4: Manual Capsule filling machine (and uniformity of mass on the capsules)

Demonstration and explanation of the operation of the tabletting machine

Measurement of the content of a tablet using spectrophotometer

Readings/Bibliography

1) P. Colombo et al., Principles and Pharmaceutical Technologies, Editrice Ambrosiana, Milan, I Ed. 2004
2) Swarbrick, BOYLAN, Encyclopedia of Pharmaceutical Technology, Dekker, 1999-2005.
3) Handbook of pharmaceutical excipients, 6th ed. Edited by Raymond C. Rowe, Paul J. Sheskey, Sian C. Owen, Pharmaceutical Press and American Pharmacists Association, Chicago, 2009.
4) Principles of Pharmaceutical Technology - M. Amorosa - Libreria Universitaria Tinarelli - Bologna.
5) Class notes

Teaching methods

theoretical lessons and Laboratory exercises

Assessment methods

Oral exam and possibly a written test (will be communicated by the teacher)

The final evaluation for the course on " Pharmaceutical Technology amd Law II" will be taken from the average of the evaluation obtained by the student in the theoretical modules 1 and 3 (Dr. L. Marchitto) and the theoretical module 2 (prof. Blasi) as well as from the passing of the practical laboratory test (dr Antonio Mazzucco)

Teaching tools

Computer: power point presentations, video projector

Office hours

See the website of Paolo Blasi

See the website of Leonardo Marchitto

See the website of Leonardo Marchitto

See the website of Antonio Mazzucco