Izazovi in vitro karakterizacije nebioloških kompleksnih lekova - primer parenteralnih preparata sa liposomskim nosačima lekovitih supstanci

Abstract

Parenteralnim putem se primenjuju različiti tipovi farmaceutskih preparata čiji sastav može biti jednostavan (vodeni rastvori) i manje ili više kompleksan (emulzije, suspenzije, liposomi kao nosači lekovitih supstanci, čestični sistemi, čvrsti implanti/implantati). Napredak u bio- i nanotehnologiji omogućio je razvoj nove klase kompleksnih lekova, bioloških i tzv. nebioloških kompleksnih lekova (i njihovih „similara”- sličnih lekova), čiji dalji razvoj se očekuje u bliskoj budućnosti, a koji se, u velikom broju slučajeva, primenjuju parenteralnim putem. Parenteralni preparati koji u svom sastavu sadrže lekovite supstance koje su inkapsulirane u nosače tipa liposoma predstavljaju nebiološke kompleksne lekove koji su do sada najduže u upotrebi i čije su osobine i definisana svojstva kvaliteta najviše ispitivana. U radu je dat pregled obaveznih i dodatnih (specifičnih) in vitro ispitivanja liposomskih nosača lekovitih supstanci za primenu parenteralnim putem. Činjenica da postupci izvođenja ovih ispitivanja u osnovi nisu propisani u relevantnim farmakopejama (Ph. Eur., USP i JP) i da se mogu značajno razlikovati između laboratorija, doprinosi velikoj varijabilnosti dobijenih rezultata i ograničenjima u njihovom međusobnom poređenju. Regulatorna tela EMA i FDA učestvovala su u pripremi određenih dokumenata i razvoju odgovarajućih standarda i smernica u pogledu ispitivanja kvaliteta farmaceutskih oblika sa liposomskim nosačima lekovitih supstanci za parenteralnu primenu.

A greater variety of pharmaceutical preparations can be administered by the parenteral route, the composition of which can be simple (aqueous solutions) and more or less complex (emulsions, suspensions, liposomes as carriers of active pharmaceutical ingredients, particle systems, solid implants/implants). In addition, advances in bio- and nano- technology have enabled the development of new classes of complex drugs, so-called non-biological complex drugs (and their similars) whose further development is expected in the near future, and which are in many cases applied by parenteral route. Parenteral preparations containing active substances encapsulated in the liposome-type carriers represent a class of non-biological complex drugs which have the longest use so far and whose properties and defined quality characteristics are being most examined. In this paper, an overview of mandatory and additional (specific) in vitro tests for parenteral liposomal drug carriers is presented. The fact that standard testing procedures are often not available in relevant pharmacopoeias (Ph. Eur., USP and JP), so that they can vary significantly between laboratories, contributes to the great variability of the results obtained and constraints in their mutual comparison. EMA and FDA, as regulatory agencies, have also participated in the preparation of certain documents and development of appropriate standards and guidelines for quality control of liposomal drug carriers for parenteral application.