In vitro-in vivo correlation for pharmaceutical alternatives of dronedarone hydrochloride

Glavni cilj tijekom razvoja dozirnih oblika u farmaceutskoj industriji je dobro razumijevanje in vitro i in vivo ponašanja dozirnih oblika. Jedan od izazova tijekom istraživanja je i koreliranje in vitro ponašanja lijeka različitih formulacija s in vivo profilom – izrada in vitro–in vivo korelacija (IVIVK). Razvoj takvog alata smanjuje vrijeme razvoja lijeka, ekonomizira resurse i omogućava bolju kvalitetu proizvoda. Sve veća upotreba IVIVK govori o njihovom velikom značaju za farmaceutsku industriju. Dronedaron-hidroklorid (DNR) kao djelatna tvar korišten je za izradu farmaceutskih alternativa oralnih dozirnih oblika; peleta, 3D tiskanih tableta i kapsula te mikrokapsula oblaganih različitim polimerima. Ispitano je in vitro oslobađanje djelatne tvari, a softverom GastroPlusTM izrađene simulacije in vivo ponašanja i pripadne farmakokinetike. Na temelju dobivenih podataka izrađene su korelacije koje opisuju ponašanje pojedinog dozirnog oblika. Rezultati ispitivanja pokazali su izvrsno slaganje za impregnirane i obložene pelete manjeg sadržaja DNR, 3D tiskane kapsule s debljinom stijenke od 0,50 mm te mikrokapsule oblagane metakrilatnim kopolimerom. Za daljnja istraživanja pogodne su i 3D tablete s najmanjom gustoćom ispune (25 %) te 3D tiskane kapsule većih debljina stijenke (0,75 i 1 mm).A key goal in pharmaceutical development of dosage forms is a good understanding of the in vitro and in vivo performance of dosage forms. One of the challenges in their research is correlating in vitro drug release information with the in vivo drug profiles – establish of in vitro–in vivo correlations (IVIVC). Such a tool shortens the drug development period, economizes the resources and leads to improved product quality. Increased activity in developing IVIVCs indicates their value to the pharmaceutical industry. Dronedarone hydrochloride was used as active pharmaceutical ingredient for making pharmaceutical alternatives of oral dosage forms; pellets, 3D printed tablets and capsules and microcapsules coated with polymers. In vitro release profiles were obtained and software GastroPlusTM was used to create simulations of in vivo behaviour and pharmacokinetics. Based on the data obtained, correlations that describe behavior of dosage forms were established. The research results showed good agreement for impregnated and coated pellets with lower dose of DNR, 3D printed capsules with 0.50 mm wall thickness and microcapsules coated with methacrylate copolymer. 3D printed tablets with 25 % of tablet infill and 3D printed capsules with thicker walls (0.75 and 1 mm) are suitable for further research