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Graphical Abstract:

Graphical Abstract:

Poor aqueous drug solubility represents a major challenge in oral drug delivery. A novel approach to overcome this challenge is drug amorphization inside a tablet, that is, on-demand drug amorphization. The amorphous form is a thermodynamically instable, disordered solid-state with increased dissolution rate and solubility compared to its crystalline counterpart. During on-demand drug amorphization, the drug molecularly disperses into a polymer to form an amorphous solid at elevated temperatures inside a tablet. This study investigates, for the first time, the utilization of photothermal plasmonic nanoparticles for on-demand drug amorphization as a new pharmaceutical application. For this, near-IR photothermal plasmonic nanoparticles were tableted together with a crystalline drug (celecoxib) and a polymer (polyvinylpyrrolidone). The tablets were subjected to a near-IR laser at different intensities and durations to study the rate of drug amorphization under each condition. During laser irradiation, the plasmonic nanoparticles homogeneously heated the tablet. The temperature was directly related to the rate and degree of amorphization. Exposure times as low as 180 s at 1.12 W cm-2laser intensity with only 0.25 wt % plasmonic nanoparticles and up to 50 wt % drug load resulted in complete drug amorphization. Therefore, near-IR photothermal plasmonic nanoparticles are promising excipients for on-demand drug amorphization with laser irradiation.

Drug release from a lipid-based drug delivery system (LbDDS) is typically studied in vitrousing a one-step intestinal digestion model. However, lately the importance of incorporating gastric digestion has been stressed. The aim of the present study was to compare a two-step gastro-intestinal (GI) in vitrodigestion model to the commonly used one-step intestinal digestion model. The models were evaluated by studying release of the model drug A1260 from two LbDDSs (F-I and F-II), for which in vivopharmacokinetic data from oral administration to beagle dogs were available. The amount of A1260 recovered in the aqueous phases during and after the GI digestion of F-I and F-II was related to the Cmaxand AUC0–48hof the plasma concentration–time profiles of each formulation and produced a rank order in vitro–in vivo(IVIV) relation. In comparison, a similar IVIV rank ordering was obtained when relating the amount of A1260 recovered in the aqueous phase prior (t= 0 min), and following 15 min of intestinal digestion, to the plasma concentration–time profiles. However, after 60 min of intestinal digestion, the LbDDSs performed equally in the one-step in vitrodigestion model, contrary to what was observed in the two-step digestion model, and in vivo. As the GI digestion model produced a clearer distinction in terms of LbDDS rank ordering of the two LbDDSs, compared to the intestinal digestion model, it was found to be a promising in vitromodel to study and estimate the LbDDS behavior in vivo.

The objective of the present study was to develop a combined dissolution-permeation model, compatible with the μDiss Profiler™ (μD/P model), to ensure continuous in situmonitoring of dissolved and permeated drug, respectively.

Lipid based drug delivery systems (LbDDSs) present an effective solution for increasing the apparent solubility and eliminating the slow dissolution process of many poorly water-soluble compounds. Typically, an initial step in designing a LbDDS is to measure the equilibrium solubility of the compound in various LbDDS excipients, which often are viscous. Equilibrium solubility is usually measured by the classical saturation shake-flask (SSF) method with centrifugation for phase separation. The concentration of the compound in the supernatant is determined as the solubility. As complete phase separation is necessary to determine the equilibrium solubility, but difficult to achieve in viscous solvents, the aim of the present study was to evaluate the effect of centrifugation speed on the measured solubility.