Problematika razvoja praškastih oblika lijeka za udisanje

Cilj istraživanja Cilj ovog rada je opisati svojstva i postupak razvoja lijekova za primjenu u dišne putove s ciljem lokalnog liječenja kroničnih bolesti pluća. Pri tome, opisat će se najvažniji čimbenici koji osiguravaju dostavu djelatne tvari izravno na mjesto djelovanja, u donje dijelove pluća. Istaknut će se najčešće korišteni sustavi za primjenu lijeka u pluća, a njihova svojstva bit će detaljno opisana analizirajući njihove prednosti i nedostatke. Krajnji cilj ovog rada je izdvojiti bitne čimbenike koje je potrebno uzeti u obzir tijekom razvoja prašaka inhalata s obzirom na njihov veliki potencijal u lokalnom liječenju kroničnih bolesti pluća. Materijal/ispitanici i metode Nakon što je Montrealskim protokolom iz 1987.g. zabranjena proizvodnja propelenata klorofluorougljika, a Kyotovskim protokolom iz 1997.g. iskazana potreba za smanjenjem primjene hidrofluorougljika kojima su zamijenjeni klorofluorougljici u stlačenim inhalatima, povećao se broj istraživanja na području razvoja prašaka inhalata. Atomizatori također nisu naišli na veću primjenu u svakodnevnom životu pacijenata s lokalnim bolestima pluća prvenstveno zbog neprikladnog prenošenja atomizatora. Iako svaki od analiziranih sustava za primjenu lijeka ima svoje prednosti, najmanje nedostataka pokazuju prašci inhalata. U istraživanju su korišteni podaci dobiveni pretraživanjem literaturnih baza podataka (Scopus i EBSCO – Elton B.Stephens Co. Inforamtion Services) prema ključnim riječima: inhalation drug development, lactose particles, inhalers characteristics, dry powder inhalers, inhalation flow. Relevantni članci kritički su proučeni s obzirom na problematiku razvoja praškastih oblika lijekova za primjenu u dišne putove. Razmotreni su zahtjevi kakvoće farmaceutskih oblika za primjenu lijeka u dišne putove u skladu s važećim europskim standardima. Problematika razvoja praškastih oblika lijeka za udisanje Rezultati Glavni čimbenici koje je potrebno uzeti u obzir tijekom razvoja prašaka inhalata su: 1) formulacija lijeka, 2) inhalator za primjenu praška inhalata, 3) tehnika udisanja bolesnika tijekom primjene lijeka. Iako postoji više strategija razvoja formulacije praška inhalata, najčešće se koristi formulacija u kojoj su čestice djelatne tvari vezane za nosač, najčešće laktozu. Također se intenzivno radi na razvoju novih, prikladnijih inhalatora čija bi učinkovitost manje ovisila o snazi udaha bolesnika. Zaključak Razvoj farmaceutskih oblika za primjenu lijeka u dišne putove je vrlo kompleksan, dugotrajan i skup postupak kojim je potrebno potvrditi učinkovitost i sigurnost primjene kao i kakvoću razvijenog farmaceutskog oblika lijeka. Potrebno je dokazati odgovarajuća svojstva formulacije te oslobađanje propisane doze lijeka preko inhalatora uzimajući u obzir ispravnu primjenu lijeka od strane bolesnika. Budućnost istraživanja usmjerena je na navedene čimbenike kako bi se razvio idealni lijek za lokalno liječenje kroničnih bolesti pluća.Objectives The aim of this work is to describe properties and development of inhalation drugs for local treatment of chronic pulmonary diseases such as astma and chronic obstructive pulmonary disease. Significant factors for inhalation drug development that ensure direct delivering of active substance into the lung will be analysed and described. The properties of the most oftenly used inhalation delivery devices will be described in details, pointing to their advantages and disadvantages. The main goal is to present significant factors in development of dry powder inhalers, taking into account their high potential in local treatment of chronic pulmonary diseases. Material/Patients and Methods Until recently, metered dose inhalers was mostly used in local treatment of chronic pulmonary diseases. The Montreal Protocol of 1987 was a global ban on the production of the five worst ozone-depleting chlorofluorocarbons (CFCs) and Kyoto Protocol of 1997 expressed need for reducing use of hydrofluorocarbons (HFCs or HFA) which have been widely investigated as alternatives to CFC propellants. After that, investigation was increased in the field of dry powder inhalers development. Nebulizers were not used as first patient choice in everyday treatment because of unsuitable transfer of device. Although each of three mentioned delivery systems has many advantages, dry powder inhalers have minimum of disadvantages. In research of this topic, data were obtained searching literature databases Scopus and EBSCO - Elton B.Stephens Co. Inforamtion Services according to key words: inhalation drug development, lactose particles, inhalers characteristics, dry powder inhalers, inhalation flow. Relevant articles were analyzed critical regarding to issues of dry powder inhalers development. All requirements which lead to inhalation drugs with appropriate quality, in line with European standards, were analyzed as well. Results Main factors which are important for dry powder inhaler development are as follows: 1) Drug formulation, 2) Drug delivery device, 3) Inhalation technic during drug administration. There are many different strategies of dry powder inhalers development. However, most often formulation of dry powder inhalers is the one with lactose as drug carrier. Investigation is intensive in the field of newer and better drug delivery devices which will be less dependent to patient inhalation force. Conclusion Inhalation drug development is very complex, longlasting and expensive process which should result with drug efficacy and safety as well as drug formulation quality. It is required to prove appropriate properties of drug formulation and drug delivery into the lung through adequate delivery device, taking into account correct drug administration. The future investigations are directed to development of mentioned significant factors which should result with ideal inhalation drug used in local treatment of chronic pulmonary diseases