Tvari koje se ekstrahiraju i otpuštaju iz farmaceutskih spremnika

professional thesis

• Author: Marko Šuvak
• Mentor: Ivica Malnar (mentor); MBZ: 174371
• Committee member: Anita Hafner (predsjednik povjerenstva)
• Committee member: Ivica Malnar (član povjerenstva); MBZ: 174371
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2017, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Cilj ovoga rada bio je prikupiti saznanja o tvarima koje se ekstrahiraju i otpuštaju iz materijala od
kojih su izrađeni farmaceutski spremnici, metodama ispitivanja ovih tvari te razmotriti pristupe
proizvođača lijekova u procjeni rizika, uz osvrt na regulatorne zahtjeve, uključujući postojeće
smjernice i preporuke.
Za izradu specijalističkog rada provedeno je pretraživanje bibliografske baze podataka (Science
Direct) prema zadanim ključnim riječima. Na temelju proučenih literaturnih podataka izvedena su
vlastita razmatranja koja su sastavni dio rasprave ovog specijalističkog rada. Također su pregledane
odgovarajuće smjernice i preporuke vezane uz farmaceutske spremnike.
Farmaceutski spremnici izrađeni od plastike i gume najznačajniji su izvor tvari koje se otpuštaju u
lijek. Proizvođač je obvezan tijekom farmaceutskog razvoja svakog lijeka provesti procjenu rizika
kako bi osigurao da je lijek opremljen u odgovarajući spremnik koji neće otpuštati tvari i posljedično
imati utjecaj na kakvoću, sigurnost i djelotvornost lijeka. Procjena rizika ponajviše ovisi o
farmaceutskom obliku i putu primjene lijeka. Raspoložive smjernice i preporuke pružaju osnovne
upute o ispitivanjima koje je potrebno provesti. Dobivene rezultate potrebno je priložiti u
dokumentaciju o lijeku koju proizvođač lijeka/podnositelj zahtjeva predaje regulatornom tijelu na
ocjenu.
Farmaceutski pripravci i njihovi sastojci mogu stupiti u doticaj s komponentama i materijalima
proizvodne opreme, kao i s komponentama primarnih i sekundarnih spremnika tijekom proizvodnje,
opremanja, skladištenja, distribucije i primjene lijeka. Takav doticaj može dovesti do interakcije
između farmaceutskog pripravka i navedenih komponenti i materijala. Jedna od takvih interakcija je
migracija ili otpuštanje tvari iz bilo kojih od ovih komponenti i materijala u farmaceutski oblik nakon
čega posljedično te tvari dolaze do pacijenta tijekom primjene lijeka. Kako bi se ocijenili sigurnosni
rizici i moguće inkompatibilnosti, potrebno je identificirati ove tvari i njihove količine koje se mogu
akumulirati u lijeku do kraja roka valjanosti. Proizvođač lijeka mora učiniti sve da koncentracija
štetnih otpuštenih tvari ne poraste do razine koja će ugroziti zdravlje i život pacijenta, a ispitivanja
treba započeti u ranoj fazi farmaceutskog razvoja lijeka.

Abstract (english)

The aim of this research was to gather information on substances that can be extracted and
leached from the material the pharmaceutical containers are made of, methods for control of these
substances and to examine the approach to the risk assessment that drug manufacturers have to make,
with an overview of the regulatory requirements, including existing guidelines and recommendations.
The bibliographic databases (Science Direct) have been searched by default keywords. On the
basis of the examined literature and its analysis the discussion has been written forming the integral
part of this research. The relevant guidelines and recommendations related to pharmaceutical
containers have also been reviewed.
Pharmaceutical containers made of plastic and elastomers are the most significant source of
substances that are leached into drug products. During the pharmaceutical development the drug
manufacturer is obliged to carry out a risk assessment to ensure that the drug is packaged in a suitable
container that will not leach substances and consequently have an impact on the quality, safety and
efficacy. Risk assessment largely depends on the pharmaceutical form and route of administration.
Available guidelines and recommendations provide basic instructions on the tests to be carried out.
The obtained results have to be included in the documentation of the drug which drug manufacturer /
applicant submits to the regulatory body for assessment.
During the production, packaging, storage, distribution and use, pharmaceutical preparations and
their ingredients can come into contact with components and materials of the manufacturing
equipment as well as those of primary and secondary packaging. Such contact can result in
interactions between the pharmaceutical preparation and the above mentioned materials. One such
interaction is the migration or leaching of the substance of any of these components and materials into
the formulation and consequently come to the patient during the administration of the drug product. In
order to assess security risks and potential incompatibilities, it is necessary to identify these substances
and their quantities that can accumulate in the drug product by the end of the shelf life. The drug
product manufacturer has to do everything to accomplish that the concentration of harmful leached
substances does not rise to a level that would endanger the health and life of the patient.

• Keywords: farmaceutski spremnici; otpuštanje tvari
• Keywords (english): pharmaceutical containers; substance leaching
• Language: croatian
• URN:NBN: urn:nbn:hr:163:594262
• Study programme: Title: Drug development; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni magistar/sveučilišna magistra razvoja lijekova (sveučilišni magistar/sveučilišna magistra razvoja lijekova)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-09-15 11:55:27