Controlling the Release of Indomethacin from Glass Solutions Layered with a Rate Controlling Membrane Using Fluid-Bed Processing. Part 1: Surface and Cross-Sectional Chemical Analysis

Abstract

den Mooter, Guy (2017) Controlling the release of indomethacin from glass solutions layered with a rate controlling membrane using fluid-bed processing. A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. AbstractFluid bed coating has been shown to be an adequate manufacturing technique to formulate poorly soluble drugs in glass solutions. Layering inert carriers with a drug-polymer mixture enables these beads to be immediately filled into capsules, thus avoiding additional, potentially destabilizing, downstream processing. In this study fluid bed coating is proposed for the production of controlled release dosage forms of glass solutions by applying a second, rate controlling membrane on top of the glass solution. Adding a second coating layer adds to the physical and chemical complexity of the drug delivery system so a thorough understanding of the physical structure and phase behavior of the different coating layers is needed. This study aimed to investigate the surface and cross-sectional characteristics (employing SEM and ToF-SIMS) of an indomethacin-polyvinylpyrrolidone (PVP) glass solution, top-coated with a release rate controlling membrane consisting of either ethyl cellulose or Eudragit RL. The implications on the addition of a pore former (PVP) and the coating medium (ethanol or water) were also considered. In addition, polymer miscibility and the phase analysis of the underlying glass solution were investigated.Significant differences in surface and cross sectional topography of the different rate controlling membranes or the way they are applied (solution vs. dispersion) were observed. These observations can be linked to the polymer miscibility differences. The presence of PVP was observed in all rate controlling membranes, even if it is not part of the coating solution. This could be attributed to residual powder presence in the coating chamber. The distribution of PVP among the sample surfaces depends on the concentration and the rate controlling polymer used.Differences can again be linked to polymer miscibility. Finally, it was shown that the underlying glass solution layer remains amorphous after coating of the rate controlling membrane, whether formed from an ethanol solution or an aqueous dispersion.4

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

“…This method has been used to formulate both controlled- and immediate-release solid dispersions 192 , 193 . Direct formation of ASD granules by this method reduces additional downstream processing steps, which aids in avoiding potential stability issues during these processes 45 , 194 . In addition, such granules allow an additional coating of suitable excipients which can control the release profiles or enhance the ASD stability 195 .…”

“…In addition, such granules allow an additional coating of suitable excipients which can control the release profiles or enhance the ASD stability 195 . For example, indomethacin–PVP ASDs prepared by coating onto sugar spheres were further coated with various polymers to achieve the desired drug release and diffusion rates 194 .…”

Development of a Surface Coating Technique with Predictive Value for Bead Coating in the Manufacturing of Amorphous Solid Dispersions

“…In addition to process-related advantages, bead coating also offers interesting opportunities concerning clinical aspects. The resulting coated pellets formulation (i.e., multiparticulate dosage form) exhibits a better spread in the gastro-intestinal tract and thus involves a reduced risk of dose-dumping [13,14]. This ASD formulation also enables more flexible dose adjustments in the clinical phases of the drug development process, as compared to a single-unit tablet formulation, and can be considered an interesting choice to compose fixed-dose combinations [15].…”

“…Despite the successful development and marketing of Sporanox ® , few research attempts thoroughly examined bead coating as an ASD manufacturing technique and scientific literature is very scarce. Moreover, the main focus in the current literature lies on simply reporting of the dissolution behavior and does not encompass a profound understanding of the physical chemistry behind the manufacturing process and formulation [13,[16][17][18]. Longer processing times, as compared to spray drying, and the challenges often encountered in finding optimal parameter settings, so that agglomeration phenomena are avoided, might serve as a possible explanation.…”

Superiority of amino-modified chiral mesoporous silica nanoparticles in delivering indometacin

“…Poorly water-soluble indometacin (IMC), the acidic nonsteroidal anti-inflammatory drug that can cause irritation of the gastrointestinal mucosa [36], was chosen as guest molecules to construct drug delivery systems. Many formulation techniques, including cyclodextrins [38], microcapsules [39], microemuslsions [25] and solid dispersions [40][41][42][43], have been widely used to establish IMC drug delivery systems. In the current stage, IMC delivery systems constructed by nanotechnology, such as PLGA nanoparticles [44] and nano-solid dispersions [45], have been reported.…”