Dissolution and permeability properties of co-amorphous formulations of hydrochlorothiazide
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CitationRuponen, Marika. Rusanen, Henna. Laitinen, Riikka. (2020). Dissolution and permeability properties of co-amorphous formulations of hydrochlorothiazide. Journal of pharmaceutical sciences, 109 (7) , 2252-2261. 10.1016/j.xphs.2020.04.008.
A biopharmaceutics classification system class IV drug, hydrochlorothiazide (HCT), was combined with co-formers of L-and d-arginine (ARG) and sodium lauryl sulphate (SLS) by cryomilling in 1:1 molar ratio. Co-amorphization was observed with L- and D-ARG. These mixtures showed a single glass transition, evidence of possible salt formation and improved physical stability at elevated temperatures and/or humidity when compared with amorphous HCT. The co-amorphous formulations, along with the combinations of HCT and HCT:L-ARG with polyvinylpyrrolidone (PVP) in 1:1 mass ratio, were investigated with a simultaneous dissolution/permeation setup using parallel artificial membrane permeability assay (PAMPA) or Madine Darby kidney cells (MDCKII) as the permeation barrier. It was observed that co-amorphization with L-ARG and D-ARG was able to induce a supersaturated state for HCT, possibly through intermolecular interactions, but there was virtually no difference between the dissolution properties of the mixtures formed with the 2 optical isomers of ARG. The permeability of HCT was found to be dependent on the dissolution properties of the formulations in both PAMPA and cellular barrier experiments. Thus, co-amorphization of HCT with L- and D-ARG demonstrated the possibility to enhance the dissolution and thereby the permeation potential of a BCS class IV drug.
Subjectsamorphism amorphous solid dispersions (ASD) arginine dissolution MDCK cells permeability solid-state
Link to the original itemhttp://dx.doi.org/10.1016/j.xphs.2020.04.008
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