Spray Drying and Scale‐Up

Dobry, Daniel E.; Settell, Dana M.; Baumann, John M.

doi:10.1002/9780470571224.pse530

Cited by 11 publications

(12 citation statements)

References 9 publications

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“…Adequate removal of the residual solvent from the final product is particularly crucial when toxic organic solvents have been employed 90 , 91 . Therefore, ASD preparation by solvent evaporation-based method is usually followed by secondary drying 92 , 93 , 94 , 95 . Other important considerations for a solvent–evaporation based method are operator exposure to harmful organic solvents and the environmental impact of solvent waste.…”

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

250

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

250

131

View full text Add to dashboard Cite

show abstract

“…Acetone and methanol (MeOH) are two preferred spray solvents, due to their high volatility, ability to dissolve a wide range of APIs and useful dispersion polymers, relatively low solution viscosity, equipment compatibility, and safety and environmental considerations [ 15 ]. The maximum dissolved solids concentration in the spray solution can be limited by the maximum viscosity for atomization, or by the solubility of the drug, or of the dispersion polymer or other formulation excipients in the spray solvent [ 16 ]. With an increasing number of NCEs exhibiting poor organic solubility, including many ‘brick dust’ APIs having very low solubility (e.g., <~1 wt%) in most solvents, the dissolved solids concentration in the spray solution is frequently limited by API solubility.…”

Section: Introductionmentioning

confidence: 99%

Acetic Acid as Processing Aid Dramatically Improves Organic Solvent Solubility of Weakly Basic Drugs for Spray Dried Dispersion Manufacture

et al. 2022

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Many active pharmaceutical ingredients (APIs) in the pharmaceutical pipeline require bioavailability enhancing formulations due to very low aqueous solubility. Although spray dried dispersions (SDDs) have demonstrated broad utility in enhancing the bioavailability of such APIs by trapping them in a high-energy amorphous form, many new chemical entities (NCEs) are poorly soluble not just in water, but in preferred organic spray drying solvents, e.g., methanol (MeOH) and acetone. Spraying poorly solvent soluble APIs from dilute solutions leads to low process throughput and small particles that challenge downstream processing. For APIs with basic pKa values, spray solvent solubility can be dramatically increased by using an acid to ionize the API. Specifically, we show that acetic acid can increase API solubility in MeOH:H2O by 10-fold for a weakly basic drug, gefitinib (GEF, pKa 7.2), by ionizing GEF to form the transient acetate salt. The acetic acid is removed during drying, resulting in a SDD of the original GEF free base having performance similar to SDDs sprayed from solvents without acetic acid. The increase in solvent solubility enables large scale manufacturing for these challenging APIs by significantly increasing the throughput and reducing the amount of solvent required.

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“…First of all, the rates of aerosol generation and transport will change. A large-scale aerosol generation is already done, especially in the context of spray drying . Additionally, the aerosol transport in the industrial process has to be in the order of tens to hundreds of meters for safety reasons since the solvents used are often flammable and have to be kept far from the deposition site.…”

Section: Process Scale-upmentioning

confidence: 99%

Mathematical Modeling for the Design and Scale-Up of a Large Industrial Aerosol-Assisted Chemical Vapor Deposition Process under Uncertainty

Filho

Carmalt

Angeli

et al. 2020

Ind. Eng. Chem. Res.

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Aerosol-assisted chemical vapor deposition (AACVD) can be used to produce coatings and thin films such as transparent conducting oxide (TCO) films, which are used in self-cleaning surfaces, solar cells, and other electronic and optoelectronic applications. A process based on AACVD consists of a number of steps: aerosol generation, aerosol transport, aerosol delivery, and chemical deposition. Predicting the behavior of such a process at an industrial scale is challenging due to a number of factors: the aerosol generation creates droplets of different sizes, losses are incurred in the transport, the delivery must evaporate the solvent to release the precursors, and the reactions on the surface of the deposition target may be complex. This paper describes a full process model, including the prediction of the size distribution of the generated aerosol, the number and size of droplets delivered, the carrier gas temperature profile at the reaction site, the solvent evaporation time, and the rate of film formation. The key modeling challenges addressed include incorporating the impact of uncertainties in parameters such as heat and mass transfer coefficients and reaction rate constants. Preliminary simulations demonstrate a proof of concept for the use of simulation for gaining insights into the feasibility of a process scale-up for an industrial-scale AACVD.

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Spray Drying and Scale‐Up

Cited by 11 publications

References 9 publications

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Acetic Acid as Processing Aid Dramatically Improves Organic Solvent Solubility of Weakly Basic Drugs for Spray Dried Dispersion Manufacture

Mathematical Modeling for the Design and Scale-Up of a Large Industrial Aerosol-Assisted Chemical Vapor Deposition Process under Uncertainty

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