| Abstract | Cilj istraživanja
Cilj ovog specijalističkog rada je opisati bitne značajke i posebnosti mikroigli kao suvremenih
načina (trans)dermalne primjene lijekova. Primjenom tekućih ili polučvrstih farmaceutskih
oblika lijekova uz pomoć mikroigli moguće je u značajnoj mjeri poboljšati ishod liječenja u
odnosu na konvencionalne načine intramuskularne i supkutane primjene lijeka.
Materijali i metode
Provedena istraživanja u okviru ovoga specijalističkog rada su teorijskog karaktera i uključuju
detaljan pregled dostupne literature prema temi istraživanja, predmetu istraživanja, autorima
i časopisu. Pretraživati će se od općih prema specijaliziranim člancima pri čemu će se
odabirati članci relevantni za problematiku ovoga specijalističkog rada.
U pretraživanju su korištene dostupne bibliografske baze podataka i servisi: PubMed,
ScienceDirect i ResearchGate, te baze podataka dostupne na web stranicama FDA, EMA –
e i ICH.
Rezultati
Koža je idealno mjesto za lokalnu i sistemsku primjenu lijekova. Iako je TDD neinvazivna
metoda dostave lijeka i osigurava određene prednosti u odnosu na oralnu i parenteralnu
primjenu, koža je impresivna barijera za prodiranje većine lijekova. Kako bi se svladala
kožna barijera te olakšao brzi i učinkoviti prijenos šireg raspona molekula, već dugi niz
godina razvijaju se odgovarajuće strategije i različiti sustavi za transdermalnu dostavu
lijekova. Mikroigle predstavljaju napredan i učinkovit sustav za TDD koji osim bezbolne
primjene posjeduje i razne druge prednosti u odnosu na druge postupke primjene lijeka kroz
kožu. Najznačajnije prednosti su izbjegavanje razgradnje lijeka u probavnom sustavu,
zaobilaženje prvog prolaska kroz jetru, poboljšana bioraspoloživost, primjena niže doze lijeka
te dobra podnošljivost bez eritrema ili edema. Nedostaci primjene lijekova mikroiglama su
manja preciznost doziranja u odnosu na supkutanu primjenu, kao i varijabilnost dubine
penetracije MN ovisno o individualnim razlikama u debljini SC i drugih slojeva kože. Također,
koža pruža otpor pri penetraciji mikroigli u kožu. MN se mogu podijeliti čvrste, šuplje i
hidrogel formirajuće MN, koje su relativno nova vrsta MN. Svaka vrsta MN ima određene
karakteristike, prednosti, ali i nedostatke. Iako postoji tržište za industrijsku proizvodnju MN
još uvijek ne postoje prihvaćeni reglatorni standardi kao ni jasni standrdi kvalitete jer još
uvijek komercijalno nisu dostupne prave MN.
Zaključak
Mikroigle se mogu uspješno koristiti za ciljanu isporuku malih molekula, makromolekula,
cjepiva i nukleinskih kiselina u specifična tkiva, te za primjenu lijekova koji se prenose
pasivnom difuzijom kroz SC. Zbog mnogobrojnih prednosti primjene mikroigli znanstvenici
pokazuju veliko zanimanje za tehnologiju mikroigli što pokazuje brzorastući broj znanstvenih
radova i patentnih publikacija pa je njihova primjena proširena i na okularnu i ciljanu dostavu
lijekova.
Tržište za uspješnu industrijsku proizvodnju mikroigli postoji, ali industrijska proizvodnja još
uvijek nije u potpunosti istražena zbog težine prebacivanja proizvodnje iz laboratorijskih
veličina serija u komercijalne te zbog ne postojanje prihvaćenih regulatornih standarda ni
jasno definiranih standarda kvalitete.
EMA je objavila novi dokument o izradi smjernica o zahtjevima kvalitete lijekova koji sadrže
medicinski proizvod za dostavu ili uporabu lijeka „EMA/CHMP/QWP/BWP/661488/2016
Concept paper on developing a guideline on Quality requirements of medicinal products
containing a device component for delivery or use of the medicinal product“. Mikroigle mogu
prodrijeti i kroz naudaljenije slojeve kože što ukazuje na drugačiji mehanizam djelovanja
naspram konvencionalnih transdermalnih flastera koji se primjenjuju samo na površinu kože
te se iz regulatorne perspektive može zaključiti da će biti definirane kao novi dozni oblik. |
| Abstract (english) | Objectives
The aim of this paper is to describe the essential characteristics and features of
microneedles as modern transdermal drug delivery system. Applications of liquid or semisolid
pharmaceutical formulation by microneedles improve the outcome of the treatment
compared to conventional methods (im. sc.) significantly. biopharmaceutical peculiarities of
inhaled medicinal products and contribute to the understanding of guidelines for preparation
of documentation for marketing authorization laid down by the European Medicines Agency
(EMA), which are related to drug development, production, quality control and stability
testing.
Materials and Methods
Research of this work is theoretical and detailed search of available literature was done by
topic and subject of research, authors and journals from general to specialized articles and
guidelines relevant to the issues of this paper. The following bibliographic databases and
services were researched: PubMed, ScienceDirect and ResearchGate and databases
available on the website of the FDA, EMA and ICH.
Results
For thousands of years the preparations are applied to the skin because the skin is an ideal
place for local and systemic drug administration. Although TDD is a non-invasive drug
delivery method and provides certain advantages over oral and parenteral administration,
skin is an impressive barrier to penetrate most of the drugs. For many years scientist are
developing strategies and various transdermal delivery systems in order to overcome the
skin barrier and to facilitate rapid and effective leakage of the broader range of molecules.
MN presents an advanced and effective TDD system that, besides painless applications,
also has various other advantages over other methods of drug administration. The most
important advantages are avoiding degradation of the drug in the gastrointestinal system,
bypassing the first passage through the liver, improved bioavailability, lower doses of the
drug and good tolerability without erythema or edema. The disadvantages of TDD by MN are
lower dosage precision compared to subcutaneous administration, as well as MN penetration
variability depending on the individual differences in the thickness of SC and other skin
layers. Also, the skin provides resistance to penetration of the MN into the skin. MN can be
divided into solid, hollow and hydrogel-forming MN, which is a relatively new species of MN.
Each type of MN has certain characteristics, advantages and disadvantages. Although there
is a market for mass production of MN, regulatory standards and clear quality standards are
not defined since the actual MN is still not commercially available.
Conclusion
Microneedles can be successfully used for the targeted delivery of small molecules,
macromolecules, vaccines and nucleic acids into specific tissues, and for the use of drug
products that pass by passive diffusion through the SC. Due to the numerous advantages of
microneedles, increasing interest of microneedle technology is registered which results with
rapidly growing number of scientific papers and patent publications, so application of
microneedles has been extended to both, ocular and targeted delivery of drug products. The
market for successful mass production of microneedles exists, but mass production has not
yet been fully explored due to the difficulty of transferring production from laboratory to
commercial batches, and because of the lack of accepted regulatory standards or clearly
defined quality standards.
EMA has published a new concept document on the development of guidelines on the quality
requirements of medicines containing a medicinal product for the delivery or use of the
medicinal product „EMA/CHMP/QWP/BWP/661488/2016 Concept paper on developing a
guideline on Quality requirements of medicinal products containing a device component for
delivery or use of the medicinal product“.
Microneedles can penetrate through the outermost layers of the skin indicating a different
mechanism of action compared to conventional transdermal patches that apply only to the
skin surface and from a regulatory perspective, it can be concluded that the MN will be
defined as a new dosage form. |
