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

Module 1 - Pharmaceutical Development (Dott. Leonardo Marchitto, 3 CFU)

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 2 - Technological controls (Dott. Leonardo Marchitto, 3 CFU)

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.

 

Modulo 3 - Drug delivery e Targeting (Prof. P. Blasi, 4 CFU)

Drug Delivery e del Drug Targeting: rational - Brief introduction on the terminology (medicinal products, conventional and modified release formulation) and on biopharmaceutics. Limits of the conventional pharmacological therapies: undesired biodistribution, low accumulation at the target site, toxicity and low compliance. Micrometrics and nanometrics carriers in drug delivery and targeting. The dimensions of objects at the micro and nano scale. Possible routes of administration of for micro- and nanocarriers.

Pharmaceutical microtechnologies - Pharmaceutical relevant microparticles and microcapsules: definitions, structures, and possible applications. Brief historical perspective on microencapsulation (es. B. Green, TMS Chang, ecc.). Application of microparticles in the pharmaceutical field: materials, preparation methods (spray-drying, spray-congealing, fluid bed, phase coacervation, solvent diffusion/evaporation, melting, ionotropic gelation) and possible administration routes. Micrometric carriers prepared by lactic and glycolic acid polymers and co-polymers (PLA/PLGA): production methods, structure, degradation and drug release. Examples of marketed medicinal products containing PLA/PLGA microparticles.

Pharmaceutical nanotechnologies and nanomedicine - Brief historical perspective on the evolution of pharmaceutical nanotechnology. The concept of drug targeting: EPR effect, passive and active targeting. General characteristics of pharmaceutical relevant nanocarriers: micelles, liposomes, dendrimers, metallic/metal oxide nanoparticles, lipid and polymer nanoparticles.

Liposomes: definition and classification. Phospholipid: structure, amphiphile behaviour in aqueous environment (soaps, phospholipids), supramolecular aggregation and critical packing parameter. Thermotropic behaviour of phospholipid membranes, main transition temperature (Tm), Tm and membrane composition (phospholipids, cholesterol). Liposomes in drug delivery and targeting. Main characteristics, production methods and loading of commercially available liposomal anthracycline formulations (Doxil^®/CAELYX^®, Myocet^® e DaunoXome^®).

Nanoparticles (NPs) in the drug targeting scenario. Polymeric NPs: definitions, polymer characteristics, structure and morphology, drug release modalities. Administration routes and NP fate: factors affecting NP fate/accumulation when administered by oral and intravenous routes. The protein corona in NP fate. Preparation methods: albumin NPs, PLGA NPs. From microemulsions and nanoemulsions to solid lipid nanoparticles (SLN). Lipid and methods to prepare SLN (hot and cold high-pressure homogenization, ultrasonication, solvent injection). Drug loading and release. Limits of the lipid crystallization (shape change, drug expulsion and aggregation) in SLN and possible solution. Differences between SLN and Nanostructured lipid carries (NLC).

 

Module 4 - Laboratory - Dr. Antonio Mazzucco (2 CFU)

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

P. Colombo et al., Principi di Tecnologia Farmaceutica, II Ed. CEA, 2015.

E. Aulton, et al., Tecnologie Farmaceutiche, EDRA, 2015.

J. Swarbrick, J.C. Boylan, Encyclopedia of Pharmaceutical Technology, Dekker, 1999-2005

R.C. Rowe et al., Handbook of pharmaceutical excipients, 6th ed. Pharmaceutical Press, 2009.

Lesson's notes.

Slides presented during the course can not be considered as a substitute of the reference texts suggested above.

Teaching methods

Lectures (module 1, 24 hours; module 2, 24 hours; and module 3, 32hours) and practical experience in the Galenic laboratory (module 4, 30 hours).

Assessment methods

Modules 1, 2 and 3 Oral exams.

Module 4 Preparation of a galenic formulation, calculation of price, packaging and labelling.

Teaching tools

Power Point presentations for the Modules 1, 2 and 3 and laboratory notes for the Module 4  (available in https://iol.unibo.it [https://iol.unibo.it/] ).

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