A Rational Design of a Biphasic Dissolution Setup—Modelling of Biorelevant Kinetics for a Ritonavir Hot-Melt Extruded Amorphous Solid Dispersion

Abstract

Biphasic dissolution systems achieved good predictability for the in vivo performance of several formulations of poorly water-soluble drugs by characterizing dissolution, precipitation, re-dissolution, and absorption. To achieve a high degree of predictive performance, acceptor media, aqueous phase composition, and the apparatus type have to be carefully selected. Hence, a combination of 1-decanol and an optimized buffer system are proposed as a new, one-vessel biphasic dissolution method (BiPHa+). The BiPHa+ was developed to combine the advantages of the well-described biorelevance of the United States Pharmacopeia (USP) apparatus II coupled with USP apparatus IV and a small-scale, one-vessel method. The BiPHa+ was designed for automated medium addition and pH control of the aqueous phase. In combination with the diode array UV-spectrophotometer, the system was able to determine the aqueous and the organic medium simultaneously, even if scattering or overlapping of spectra occurred. At controlled hydrodynamic conditions, the relative absorption area, the ratio between the organic and aqueous phase, and the selected drug concentrations were identified to be the discriminating factors. The performance of a hot-melt extruded ritonavir-containing amorphous solid dispersion (ritonavir-ASD) was compared in fasted-state dissolution media leading to different dissolution-partitioning profiles depending on the content of bile salts. An advanced kinetic model for ASD-based well described all phenomena from dispersing of the ASD to the partitioning of the dissolved ritonavir into the organic phase.

Impact of HPMCAS on the Dissolution Performance of Polyvinyl Alcohol Celecoxib Amorphous Solid Dispersions

“…Lecithin and sodium taurocholate were purchased from Alfa Aesar (Haverhill, MA, USA). FaSSIF-V2 medium was prepared according to Denninger et al [30], in henceforth will be referred to as FaSSIF.…”

“…Biphasic dissolution was carried out using the BiPha+ apparatus, which was previously developed in our group [ 30 ]. Briefly, 50 mL of aqueous phase (FaSSIF adjusted to pH 6.8) was placed in the dissolution vessel at a temperature of 37 °C.…”

“…Biphasic dissolution was carried out using the BiPha+ apparatus, which was previously developed in our group [30]. Briefly, 50 mL of aqueous phase (FaSSIF adjusted to pH 6.8) was placed in the dissolution vessel at a temperature of 37 • C. Subsequently, the formulation to be tested was added to the aqueous phase and after 30 min 1-decanol was overlaid onto the aqueous layer.…”

Developing HME-Based Drug Products Using Emerging Science: a Fast-Track Roadmap from Concept to Clinical Batch

“…The exact in vitro/ex vivo simulation of in vivo situations is challenging since disintegration, drug solubilization, ASD surface plasticization, and supersaturation are connected events. However, the reasonable accuracy obtained by combining an advanced in vitro characterization with in silico models helps the formulators to choose and/or to modify the functional excipients, drug loading, and processing parameters while scaling up the HME process for the production of clinical supplies (68,69).…”

Impact of bile salts and a medium chain fatty acid on the physical properties of self-emulsifying drug delivery systems

“…To investigate drug release from SEDDS in the presence of bile salts and decanoate, we employed a biphasic release setup [24] with some modifications to ensure sink conditions without an extensive dilution of SEDDS. Quinine, a lipophilic drug with a logP value of 2.9 (octanol/water) was used as a model drug.…”