Hot Melt Extruded Posaconazole-Based Amorphous Solid Dispersions—The Effect of Different Types of Polymers

Abstract

Four model polymers, representing (i) amorphous homopolymers (Kollidon K30, K30), (ii) amorphous heteropolymers (Kollidon VA64, KVA), (iii) semi-crystalline homopolymers (Parteck MXP, PXP), and (iv) semi-crystalline heteropolymers (Kollicoat IR, KIR), were examined for their effectiveness in creating posaconazole-based amorphous solid dispersions (ASDs). Posaconazole (POS) is a triazole antifungal drug that has activity against Candida and Aspergillus species, belonging to class II of the biopharmaceutics classification system (BCS). This means that this active pharmaceutical ingredient (API) is characterized by solubility-limited bioavailability. Thus, one of the aims of its formulation as an ASD was to improve its aqueous solubility. Investigations were performed into how polymers affected the following characteristics: melting point depression of the API, miscibility and homogeneity with POS, improvement of the amorphous API’s physical stability, melt viscosity (and associated with it, drug loading), extrudability, API content in the extrudate, long term physical stability of the amorphous POS in the binary drug–polymer system (in the form of the extrudate), solubility, and dissolution rate of hot melt extrusion (HME) systems. The obtained results led us to conclude that the physical stability of the POS-based system increases with the increasing amorphousness of the employed excipient. Copolymers, compared to homopolymers, display greater homogeneity of the investigated composition. However, the enhancement in aqueous solubility was significantly higher after utilizing the homopolymeric, compared to the copolymeric, excipients. Considering all of the investigated parameters, the most effective additive in the formation of a POS-based ASD is an amorphous homopolymer—K30.

Advances in the development of amorphous solid dispersions: The role of polymeric carriers

“…The increase of amorphousness of the polymer enhanced the physical stability of the ASDs. Compared to homopolymers, the ASDs formulated with copolymers exhibited greater homogeneity but less enhancement in aqueous solubility [270] .…”

“…constructed thermodynamic phase diagrams for ASD systems and utilized them to guide HME process [269] . They found that this approach ensured the desired quality of ASDs [269] .The type of polymers can affect the miscibility and homogeneity of ASD prepared by HME [270] . Kramarczyk et al.…”

“…Kramarczyk et al. studied the impact of four model polymers (Kollidon Ⓡ K30, Kollidon Ⓡ VA64, Parteck MXP and Kollicoat IR) on the physicochemical properties of the posaconazole ASD systems manufactured by HME [270] . The increase of amorphousness of the polymer enhanced the physical stability of the ASDs.…”

Polyvinyl Alcohol, a Versatile Excipient for Pharmaceutical 3D Printing

“…The value of this blend’s viscosity was between 10 3 and 10 4 Pa⋅s, in the suitable range that was also determined by other researchers beforehand. [ 59 ].…”

Polyelectrolyte-Complex-Based Hydrogel Inserts for Vaginal Delivery of Posaconazole and Probiotics

“…POS showed a sharp endothermic peak at 170.3 • C, indicating the melting point and crystalline nature of the POS. Kramarczyk et al [25] described this endothermic peak as the melting event of POS polymorphic form I, which is anhydrous. A small peak before the melting of drug, at 109.7 • C, indicated nematic phase transition, which is characteristic of POS and other triazoles [26].…”