Investigating the Potential of Ethyl Cellulose and a Porosity-Increasing Agent as a Carrier System for the Formulation of Amorphous Solid Dispersions

Abstract

In the present work, an insoluble polymer, i.e., ethyl cellulose (EC), was combined with the water-soluble polyvinylpyrrolidone (PVP) as a carrier system for the formulation of amorphous solid dispersions. The rationale was that by conjoining these two different types of carriers a more gradual drug release could be created with less risk for precipitation. Our initial hypothesis was that upon contact with the dissolution medium, PVP would be released, creating a porous EC matrix through which the model drug indomethacin could diffuse. On the basis of observations of EC as a coating material, the effect of the molecular weight of PVP, and the ratio of EC/PVP on the miscibility of the polymer blend, the solid state of the solid dispersion and the drug release from these solid dispersions were investigated. X-ray powder diffraction, modulated differential scanning calorimetry, and solid-state nuclear magnetic resonance were used to unravel the miscibility and solid-state properties of these blends and solid dispersions. Solid-state nuclear magnetic resonance appeared to be a crucial technique for this aspect as modulated differential scanning calorimetry was not sufficient to grasp the complex phase behavior of these systems. Both EC/PVP K12 and EC/PVP K25 blends were miscible over the entire composition range, and addition of indomethacin did not alter this. Concerning the drug release, it was initially thought that more PVP would lead to faster drug release with a higher probability that all of the drug molecules would be able to diffuse out of the EC network as more pores would be created. However, this view on the release mechanism appeared to be too simplistic as an optimum was observed for both blends. On the basis of this work, it could be concluded that drug release from this complex ternary system was affected not only by the ratio of EC/PVP and the molecular weight of PVP but also by interactions between the three components, the wettability of the formulations, and the viscosity layer that was created around the particles.

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

“…To improve the drug release from these systems, a hydrophilic polymeric carrier was used as a pore former by some researchers [ 82 , 83 ]. In a similar study by Everaerts et al [ 84 ], Indomethacin ASD was manufactured using spray-drying, using Ethyl cellulose as a polymeric backbone and investigating two different grades of PVP (povidone), PVPK12 and PVP K25, respectively as water-soluble pore formers. Owing to the poor solubility of the drug in acidic media, the authors explored various amounts of the water-soluble carrier (PVP K12 and PVP K25) to evaluate its effect on improving drug release in acidic media.…”

Enhanced Oral Bioavailability of Rivaroxaban-Loaded Microspheres by Optimizing the Polymer and Surfactant Based on Molecular Interaction Mechanisms

“…The paddle speed and temperature were maintained at 50 rpm and 37 ± 0.5 °C, respectively. The dissolution medium (3 mL) was collected at several time points (5,10,15,30,45,60, and 120 min) and then filtered through a nylon filter (0.45 μm). The drug concentration in the medium was analyzed using HPLC, as described above.…”

“…Various formulation strategies have been used to overcome the poor aqueous solubility of RXB, including co-crystallization, self-microemulsifying drug delivery systems, micronization, cyclodextrin inclusion, micelle solubilization, solid dispersion, , and encapsulation in nanoparticles . Among the various solubilizing techniques available to increase solubility and dissolution, solid dispersion is commonly used to enhance the aqueous solubility, dissolution, and oral bioavailability of RXB, a poorly water-soluble drug. , Solid dispersion is generally used for a group of solid products, such as hydrophobic drugs, consisting of a hydrophilic matrix and two or more other components . Amorphous solid dispersion is a promising strategy to improve the solubility and bioavailability of poorly soluble drugs.…”

“…9 Among the various solubilizing techniques available to increase solubility and dissolution, solid dispersion is commonly used to enhance the aqueous solubility, dissolution, and oral bioavailability of RXB, a poorly water-soluble drug. 3,10 Solid dispersion is generally used for a group of solid products, such as hydrophobic drugs, consisting of a hydrophilic matrix and two or more other components. 11 Amorphous solid dispersion is a promising strategy to improve the solubility and bioavailability of poorly soluble drugs.…”

Role of Microstructure in Drug Release from Chitosan Amorphous Solid Dispersions

“…In turn, the solubility of the polymer itself is an important factor in achieving an adequate release of the active principle by maintaining supersaturation in solution, and it can condition the release mechanism. An adequate selection of the polymer is crucial to achieve an effective controlled release behaviour [ 4 ].…”