Čvrste disperzije sa karbamazepinom: optimizacija formulacija, karakterizacija i ispitivanje dugoročne stabilnosti
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Abstract
U ovom radu je izvršena optimizacija formulacija čvrstih disperzija sa karbamazepinom, primenom metode D-optimalnog eksperimentalnog dizajna smeše, u cilju povećanja brzine rastvaranja navedene teško rastvorljive aktivne supstance. Primenom metode eksperimentalnog dizajna smeše, formulisane su čvrste disperzije variranjem udela karbamazepina (30‑50 %), Gelucire® 44/14 (20-40 %) i polimera Soluplus® (30-50 %) (ulazni parametri). Izrađeno je 16 formulacija, iz kojih je ispitana in vitro brzina rastvaranja karbamazepina. Kao izlazni parametri praćeni su procenti rastvorenog karbamazepina, nakon 10, 20, 30, 45 i
60 minuta. Najveći udeo oslobođenog karbamazepina iz čvrstih disperzija (preko 80 % zа
30 minutа) se postiže pri udelima aktivne supstance od oko 40 %, Soluplus® oko 45 % i Gelucire® 44/14 oko 25%. Nakon obrade podataka i optimizacije, iz različitih delova optimizacione oblasti odabrane su 3 formulacije za dalja ispitivanja. Rezultati ispitivanja odabranih optimizovanih uzoraka čvrstih disperzija nakon izrade, kao i nakon skladištenja 24 meseca pod ambijentalnim uslovima (25 °C, 40 % RH), dobijeni primenom metoda diferencijalne skenirajuće kalorimetrije (DSC), infracrvene spektroskopije sa Furijeovom transformacijom (FT-IR) i Ramanske spektoskopije potvrdili su njihovu stabilnost i očuvanje karbamazepina u polimrfnom obliku III, jedinom farmakološki aktivnom obliku. Primenom PAMPA (eng. Parallel Artificial-Membrane Permeability Assay) testa pokazano je da je u dve, od tri ispitivane optimizovane čvrste disperzije očuvana, odnosno blago povećana permeabilnost karbamazepina.
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