Development of a Control Strategy for Benzene Impurity in HPMCAS-Stabilized Spray-Dried Dispersion Drug Products Using a Science-Based and Risk-Based Approach

Yue, Hongfei; Nicholson, Sarah J.; Young, Joel; Hsieh, Daniel; Ketner, Rodney J.; Hall, R. G.; Sackett, Jeremy; Banks, Elizabeth; Castoro, John A.; Randazzo, Michael E.

doi:10.1007/s11095-015-1649-7

Cited by 4 publications

(2 citation statements)

References 7 publications

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“…The solvent should not affect the physical or chemical stability of the formulation constituents during the manufacturing process before being evaporated from the system. The amount of residual solvent(s) in the final ASD products must be within the acceptable values of the International Council for Harmonization Q3C (R6) guideline 88 , 89 . This guideline defines three different classes of solvents: Classes I, II, and III.…”

Section: Manufacturing Methods For Preparing Amorphous Solid Dispersionsmentioning

confidence: 99%

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Bhujbal

Mitra

Jain

et al. 2021

Acta Pharmaceutica Sinica B

276

131

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Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

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Section: Manufacturing Methods For Preparing Amorphous Solid Dispersionsmentioning

confidence: 99%

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Bhujbal

Mitra

Jain

et al. 2021

Acta Pharmaceutica Sinica B

276

131

View full text Add to dashboard Cite

show abstract

“…A strategy to mitigate the risk of ICH Class 1 impurity benzene reaching drug product in spray dried dispersions was reported (Yue et al, 2015). The risk assessment considered the likelihood of residual benzene from primary spray solvents being concentrated in the product.…”

Section: Selecting An Appropriate Solvent and Monitoring Residual Sol...mentioning

confidence: 99%

Recent strategies in spray drying for the enhanced bioavailability of poorly water-soluble drugs

Davis

Walker

2018

Journal of Controlled Release

130

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Poorly water-soluble drugs are a significant and ongoing issue for the pharmaceutical industry. An overview of recent developments for the preparation of spray-dried delivery systems is presented. Examples include amorphous solid dispersions, spray dried dispersions, microparticles, nanoparticles, surfactant systems and self-emulsifying drug delivery systems. Several aspects of formulation are considered, such as pre-screening, choosing excipient(s), the effect of polymer structure on performance, formulation optimisation, ternary dispersions, fixed-dose combinations, solvent selection and component miscibility. Process optimisation techniques including nozzle selection are discussed. Comparisons are drawn with other preparation techniques such as hot melt extrusion, freeze drying, milling, electro spinning and film casting. Novel analytical and dissolution techniques for the characterization of amorphous solid dispersions are included. Progress in understanding of amorphous supersaturation or recrystallisation from solution gathered from mechanistic studies is discussed. Aspects of powder flow and compression are considered in a section on downstream processing. Overall, spray drying has a bright future due to its versatility, efficiency and the driving force of poorly soluble drugs.

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The Secondary Drying and the Fate of Organic Solvents for Spray Dried Dispersion Drug Product

et al. 2014

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The diffusion process is dependent upon temperature. The key to a successful scale up of the secondary drying is to control the drying temperature. The fate of primary solvents including methanol and acetone, and their potential impurity such as benzene can be described by the Fickian diffusion model. A mathematical relationship based upon the ratio of diffusion coefficient was established to predict the benzene concentration from the fate of the primary solvent during the secondary drying process.

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Development of a Control Strategy for Benzene Impurity in HPMCAS-Stabilized Spray-Dried Dispersion Drug Products Using a Science-Based and Risk-Based Approach

Abstract: Two critical control points were established to eliminate any risk of residual benzene reaching patients: (1) upstream control of benzene in solvents (≤10 ppm) and (2) IPC of residual solvents in polymer-stabilized SDDs.

Cited by 4 publications

References 7 publications

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Recent strategies in spray drying for the enhanced bioavailability of poorly water-soluble drugs

The Secondary Drying and the Fate of Organic Solvents for Spray Dried Dispersion Drug Product

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