Comparative Assessment of Miniaturized Screening Approaches for Selection of Polymers for Amorphous Drug Stabilization

Banda, Alamelu; Manchanda, Arushi; Zhang, Wei; Alba, Grace May; Nagapudi, Karthik

doi:10.1016/j.xphs.2017.11.006

Cited by 9 publications

(4 citation statements)

References 30 publications

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“…One method to mitigate this issue involves addition of polymeric crystallization inhibitors to stabilize amorphous solids, which form so-called ASDs. [15][16][17][18][19] It has been reported that the high physical stability of ASDs are due to molecular interactions between API and polymer. [20][21][22] For example, hydrogen bonding could improve the structural properties and stability of solid dispersions.…”

Section: Introductionmentioning

confidence: 99%

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

Zheng

Lin

Capece

et al. 2019

Journal of Pharmaceutical Sciences

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The effect of particle size on the dissolution behavior of the particles of amorphous solid dispersions (ASDs) of griseofulvin (GF), with 0%-50% Kollidon ® VA 64 as a crystallization inhibitor is investigated. Both the final dissolved GF concentration and the dissolution rate of GF ASDs were found to be inversely proportional to the particle size. The solution concentrations for the smallest (45-75 mm) size group with different polymer loadings were significantly higher than those for the largest (250-355 mm) group regardless of the initial GF amount. Specifically, the dissolution rate of GF ASDs with 50% polymer loading for the finest group was 2.7 times higher than for the largest group under supersaturating conditions. The rates of dissolution and recrystallization were assessed through surface concentration (C s) and Avrami recrystallization rate kinetics, where the solid-state recrystallization was confirmed using Raman spectroscopy. Outcomes indicated that particle size reduction enhanced ASD drug loading by reducing the amount of polymer necessary as finest size ASDs initially dissolve faster, negating their higher recrystallization rate. Kollidon® VA 64 at 30% loading was sufficient to inhibit the GF recrystallization. Overall, the combination of particle size reduction and recrystallization inhibition is effective for improved dissolution behavior of GF ASDs.

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Section: Introductionmentioning

confidence: 99%

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

Zheng

Lin

Capece

et al. 2019

Journal of Pharmaceutical Sciences

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“…Inherently, increased amounts of data are necessary to describe such a system with a sufficient generalization for future applications. This can be mitigated by standardized screenings [29,80] with a high throughput or robotic laboratory automation of such formulation assays. In those cases, established data-driven models can reduce the future experimental effort for new active pharmaceutical ingredients (API).…”

Section: Conclusion and Unmet Needsmentioning

confidence: 99%

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

Uhlemann

Diedam

Hoheisel³

et al. 2020

Pharmaceutics

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Crystalline organic nanoparticles and their amorphous equivalents (ONP) have the potential to become a next-generation formulation technology for dissolution-rate limited biopharmaceutical classification system (BCS) class IIa molecules if the following requisites are met: (i) a quantitative understanding of the bioavailability enhancement benefit versus established formulation technologies and a reliable track record of successful case studies are available; (ii) efficient experimentation workflows with a minimum amount of active ingredient and a high degree of digitalization via, e.g., automation and computer-based experimentation planning are implemented; (iii) the scalability of the nanoparticle-based oral delivery formulation technology from the lab to manufacturing is ensured. Modeling and simulation approaches informed by the pharmaceutical material science paradigm can help to meet these requisites, especially if the entire value chain from formulation to oral delivery is covered. Any comprehensive digitalization of drug formulation requires combining pharmaceutical materials science with the adequate formulation and process technologies on the one hand and quantitative pharmacokinetics and drug administration dynamics in the human body on the other hand. Models for the technical realization of the drug production and the distribution of the pharmaceutical compound in the human body are coupled via the central objective, namely bioavailability. The underlying challenges can only be addressed by hierarchical approaches for property and process design. The tools for multiscale modeling of the here-considered particle processes (e.g., by coupled computational fluid dynamics, population balance models, Noyes–Whitney dissolution kinetics) and physiologically based absorption modeling are available. Significant advances are being made in enhancing the bioavailability of hydrophobic compounds by applying innovative solutions. As examples, the predictive modeling of anti-solvent precipitation is presented, and options for the model development of comminution processes are discussed.

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“…To enable effective and efficient development of SD for early stage research compound, several studies reported miniaturized method for polymer screening of solid dispersion. 2,14,[18][19][20] In this study, solvent evaporation method followed by miniaturized two-step kinetic solubility was employed to facilitate the polymer screening with minimal consumption of the compound which is a key element in SD formulation. This method allows quick identification of the most promising polymers that could improve the kinetic solubility in biorele-vant media.…”

Section: Sd Formulation Screening By Solvent Evaporationmentioning

confidence: 99%

Preliminary Development of Solid Dispersion for an Insoluble Compound ZL006 by Miniaturized Hot Melt Extrusion

Zhang

Luan

et al. 2019

Pharmaceutical Fronts

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The purpose of this study was to develop a solid dispersion (SD) by miniaturized hot-melt extrusion (HME) for an insoluble molecule ZL006 which showed potency of increasing leukocytes. A preliminary formulation screening was conducted using solvent evaporation method. The selected SD formulation was further optimized and scaled up using a miniaturized twin-screw extruder. Solid-state characterizations of the scale-up SD and its corresponding physical mixture (PM) were performed by X-ray powder diffraction (XRPD), modulated differential scanning calorimetry (mDSC), and Fourier's transform infrared spectroscopy (FTIR). XRPD and mDSC results indicated the formation of amorphous SD. FTIR spectrum indicated the possible hydrogen bond formation between the compound and the excipient. A discriminating non-sink condition micro-dissolution of SD showed the fast release of ZL006 which was approximately two-fold and three-fold of dissolution of PM and pure crystalline compound, respectively. The preliminary in vivo pharmacokinetics (PK) study in rats showed 71% oral bioavailability from the SD, while the bioavailability of ZL006 conventional suspension was less than 1%. Thus, an SD formulation for ZL006 with improved solubility and bioavailability was developed by miniaturized HME with minimal amount of compound at early preclinical stage, which could enable the preclinical evaluation.

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Comparative Assessment of Miniaturized Screening Approaches for Selection of Polymers for Amorphous Drug Stabilization

Cited by 9 publications

References 30 publications

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

Preliminary Development of Solid Dispersion for an Insoluble Compound ZL006 by Miniaturized Hot Melt Extrusion

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