Čvrste disperzije sa karbamazepinom: optimizacija formulacija, karakterizacija i ispitivanje dugoročne stabilnosti

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Marko Zoran Krstić
Igor Lukić
Alma Bušatlić
Nenad Lazarević
Dragana Vasiljević

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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How to Cite
Krstić, M. Z., Lukić, I., Bušatlić, A., Lazarević, N., & Vasiljević, D. (2018). Čvrste disperzije sa karbamazepinom: optimizacija formulacija, karakterizacija i ispitivanje dugoročne stabilnosti. HEMIJSKA INDUSTRIJA (Chemical Industry), 72(4), 191–204. https://doi.org/10.2298/HEMIND171025013K
Section
Chemical Engineering - Pharmaceutical Engineering
Author Biographies

Marko Zoran Krstić, Farmaceutski fakultet, Katedra za farmaceutsku tehnologiju i kozmetologiju, Univerzitet u Beogradu, Vojvode Stepe 450, 11221 Beograd

Katedra za farmaceutsku tehnologiju i kozmetologiju

Dragana Vasiljević, Farmaceutski fakultet, Katedra za farmaceutsku tehnologiju i kozmetologiju, Univerzitet u Beogradu, Vojvode Stepe 450, 11221 Beograd

Katedra za farmaceutsku tehnologiju i kozmetologiju

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