Polymer incorporation method affects the physical stability of amorphous indomethacin in aqueous suspension

Surwase, Sachin Appasaheb; Itkonen, Lauri; Aaltonen, Jaakko; Saville, Dorothy J.; Rades, Thomas; Peltonen, Leena; Strachan, Clare J.

doi:10.1016/j.ejpb.2015.06.005

Cited by 40 publications

(26 citation statements)

References 42 publications

(29 reference statements)

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“…9A). It is known that molecular mixing between IND and SOL in one-phase SD completely inhibited drug release (Surwase et al, 2015). The release of IND from the corresponding PMs within the first 10 min was close to that obtained with pure γ-IND at pH 6.8 (11.8 ± 1.7% and 7.1 ± 0.6%).…”

Section: Dissolutionsupporting

confidence: 67%

“…The desired SD structure for improving drug dissolution would be one-phase homogeneous solid solution (Brough and Williams, 2013). However, the opposite effect has been observed with one-phase SDs with no detectable drug dissolution due to the formation hydrogen bonds between the drug and carrier material (Surwase et al, 2015). Two-phase glassy suspensions and amorphous precipitation systems may circumvent this problem, and thus, they have also a great potential to achieve these goals (Thommes et al, 2011;Thommes, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions

Semjonov

Salm

Lipiäinen

et al. 2018

International Journal of Pharmaceutics

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Solid dispersions (SDs) hold a proven potential in formulating poorly water-soluble drugs. The present paper investigates the interfacial phenomena associated with the bulk powder flow, water sorption, wetting and dissolution of the SDs prepared by a modified melt and quench-cooling (QC) method. Poorly water-soluble indomethacin (IND) was QC molten with solubilizing graft copolymer (Soluplus®) or polyol sugar alcohol (xylitol, XYL). The interfacial interactions of SDs with air/water were found to be reliant on the type (amorphous/crystalline) and amount of the carrier material used. The final SDs were composed of fused agglomerates (SOL) or large jagged particles (XYL) with good wetting and powder flow properties. The initial dissolution of IND was accelerated by both carrier materials studied. The QC molten SDs with amorphous Soluplus® significantly improved the dissolution rate of IND at pH 6.8 (79.9 ± 0.2% at 30 min) compared to that of pure crystalline drug. The substantial improvement in the dissolution rate of IND was in connection with the amorphous state of the drug being stabilized by Soluplus® in the QC molten SDs. However, it is evident that a strong H-bond formation between the components in some regions of the QC molten SDs can limit the dissolution of IND. The QC molten two-phase SDs with a polyol carrier (XYL) showed rapid and continuous drug release without reaching a plateau.

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Section: Dissolutionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions

Semjonov

Salm

Lipiäinen

et al. 2018

International Journal of Pharmaceutics

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“…98 Polymeric excipients that increase aqueous solubility (by inhibiting precipitation of the dissolved drug) can retard the nucleation rate by decreasing the free drug concentration available for nuclei/ seed formation. 99 Polymer also increases the viscosity of the system which may alter the frequency of atomic/molecular transport at the surface of the nucleus. 100 Moreover, they have sufficiently high configurational entropy due to their large, complex, and flexible structures; their high molecular weights; and their ability to exist in many conformations.…”

Section: Crystallization Inhibitionmentioning

confidence: 99%

Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs

Baghel

Cathcart

O’Reilly

2016

Journal of Pharmaceutical Sciences

749

452

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Poor water solubility of many drugs has emerged as one of the major challenges in the pharmaceutical world. Polymer-based amorphous solid dispersions have been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. The principle drawback of this approach is that they can lack necessary stability and revert to the crystalline form on storage. Significant upfront development is, therefore, required to generate stable amorphous formulations. A thorough understanding of the processes occurring at a molecular level is imperative for the rational design of amorphous solid dispersion products. This review attempts to address the critical molecular and thermodynamic aspects governing the physicochemical properties of such systems. A brief introduction to Biopharmaceutical Classification System, solid dispersions, glass transition, and solubility advantage of amorphous drugs is provided. The objective of this review is to weigh the current understanding of solid dispersion chemistry and to critically review the theoretical, technical, and molecular aspects of solid dispersions (amorphization and crystallization) and potential advantage of polymers (stabilization and solubilization) as inert, hydrophilic, pharmaceutical carrier matrices. In addition, different preformulation tools for the rational selection of polymers, state-of-the-art techniques for preparation and characterization of polymeric amorphous solid dispersions, and drug supersaturation in gastric media are also discussed.

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“…These differences were attributed to the differing molecular interactions between the drug and polymer molecules in the various solvents. In a recent study, stability of amorphous indomethacin and solubility in supersaturated suspensions was found to depend on the polymer and method of incorporation …”

Section: Introductionmentioning

confidence: 99%

Atypical effects of incorporated surfactants on stability and dissolution properties of amorphous polymeric dispersions

Al-Obaidi

Lawrence

Buckton

2016

Journal of Pharmacy and Pharmacology

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Polymer incorporation method affects the physical stability of amorphous indomethacin in aqueous suspension

Cited by 40 publications

References 42 publications

Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions

Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions

Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs

Atypical effects of incorporated surfactants on stability and dissolution properties of amorphous polymeric dispersions

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