Abstract
Despite the fact that an amorphous solid dispersion (ASD)-coated pellet formulation offers potential advantages regarding the minimization of physical stability issues, there is still a lack of in-depth understanding of the bead coating process and its value in relation to spray drying. Therefore, bead coating and spray drying were both evaluated for their ability to manufacture high drug-loaded ASDs and for their ability to generate physically stable formulations. For this purpose, naproxen (NAP)–poly(vinyl-pyrrolidone-co-vinyl acetate) (PVP-VA) was selected as an interacting drug–polymer model system, whilst naproxen methyl ester (NAPME)–PVP-VA served as a non-interacting model system. The solvent employed in this study was methanol (MeOH). First, a crystallization tendency study revealed the rapid crystallization behavior of both model drugs. In the next step, ASDs were manufactured with bead coating as well as with spray drying and for each technique the highest possible drug load that still results in an amorphous system was defined via a drug loading screening approach. Bead coating showed greater ability to manufacture high drug-loaded ASDs as compared to spray drying, with a rather small difference for the interacting drug–polymer model system studied but with a remarkable difference for the non-interacting system. In addition, the importance of drug–polymer interactions in achieving high drug loadings is demonstrated. Finally, ASDs coated onto pellets were found to be more physically stable in comparison to the spray dried formulations, strengthening the value of bead coating for ASD manufacturing purposes.
Highlights
Publisher’s Note: MDPI stays neutralAt present, about 90% of new chemical entities (NCE) in drug discovery pipelines are characterized by a low aqueous solubility [1,2]
Regarding the classification set forth by Van Eerdenbrugh et al, it can be concluded that both model compounds can be classified as glass forming ability (GFA) Class I compounds in MeOH [20,21]
A direct comparison was made between bead coating and spray drying related to their ability to manufacture high drug-loaded amorphous solid dispersion (ASD) in combination with a physical stability evaluation of the resulting formulations
Summary
Publisher’s Note: MDPI stays neutralAt present, about 90% of new chemical entities (NCE) in drug discovery pipelines are characterized by a low aqueous solubility [1,2]. One of the most successful approaches is to disperse a poorly water-soluble drug on a molecular level within an inert polymer matrix in the solid state, thereby creating an amorphous solid dispersion (ASD) [4,5]. An ASD or glass solution is, only thermodynamically stable (i.e., the drug will never crystallize), in case the drug content is below its thermodynamic solubility limit in the polymer [10,11]. The persisting trend to lower the pill burden to promote patient therapeutic compliance requires the implementation of as high as possible drug loadings within the polymer [5,12,13]. Such high drug-loaded ASDs can imply physical stability issues during down-stream processing, with regard to jurisdictional claims in published maps and institutional affiliations
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
