Abstract
Fluid bed coating has been shown to be a suitable 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 scanning electron microscopy (SEM) and time of flight secondary ion mass spectrometry (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 of 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.
Highlights
The potential of solid dispersions to increase the apparent solubility/dissolution rate and the bio-availability of biopharmaceutics classification system (BCS) class II drugs has been widely demonstrated in the last couple of decades, there is still a huge discrepancy in the research input and the commercially available output
We recently reported that INDO-PVP coated beads (30-70% w/w) are forming a glass solution, i.e. one phase systems characterized by a single Tg where the drug is molecularly dispersed into the polymer matrix[12]
The composition and polymer distribution of complex coated systems was elucidated by combining complementary solid state analytical techniques
Summary
The potential of solid dispersions to increase the apparent solubility/dissolution rate and the bio-availability of biopharmaceutics classification system (BCS) class II drugs has been widely demonstrated in the last couple of decades, there is still a huge discrepancy in the research input and the commercially available output. Can long term stability issues potentially arise, processing solid dispersion powders into their final dosage form can lead to phase separation, as recently shown by Worku et al during the compression of Naproxen polyvinylpyrrolidone (PVP) solid dispersions[1] This is a hurdle which can be overcome by coating solid dispersions onto inert carriers and surpassing major additional downstream processing steps. Coated pellets in the size range of 100μm-1mm for controlled release purposes have already been demonstrated as beneficial as compared to controlled release coated tablets This is thought to be as they are less prone to variability in stomach emptying rates in the fasted state[2]. The surface of amorphous solid dispersion formulations has been shown to be more vulnerable to crystallization of the amorphous drug phase[5], an additional coating layer could potentially stabilize these formulations
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