Trehalose Limits BSA Aggregation in Spray-Dried Formulations at High Temperatures: Implications in Preparing Polymer Implants for Long-Term Protein Delivery

Rajagopal, Karthikan; Wood, Joanne V.; Tran, Benjamin; Patapoff, Thomas W.; Nivaggioli, Thierry

doi:10.1002/jps.23634

Cited by 40 publications

(30 citation statements)

References 38 publications

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“…Several agents have been developed to increase the stability of biologics 182 . These include the use of small sugars such as trehalose 183,184 and polysaccharides such as dextrans 185 . Pluronics are also used to reduce the tendency to aggregate.…”

Section: Figurementioning

confidence: 99%

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Mitragotri

Burke

Langer

2014

Nat Rev Drug Discov

1,382

1,037

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The formulation and delivery of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, poses substantial challenges owing to their large size and susceptibility to degradation. In this Review we highlight recent advances in formulation and delivery strategies — such as the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs — and discuss their advantages and limitations. We also highlight current and emerging delivery routes that provide an alternative to injection, including transdermal, oral and pulmonary delivery routes. In addition, the potential of targeted and intracellular protein delivery is discussed.

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Section: Figurementioning

confidence: 99%

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Mitragotri

Burke

Langer

2014

Nat Rev Drug Discov

1,382

1,037

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show abstract

“…With advances in formulation design, the complexity of the formulations that are designed to enhance the solubility of insoluble drugs and provide greater stability for concentrated biologicals which tend to undergo aggregation, deamination, denaturation, hydrolysis, or oxidation has also changed dramatically (2)(3)(4). Multiple excipients, agents, and environmental factors have been investigated that can ensure both physical and chemical stability of biopharmaceuticals including the use of small sugars such as trehalose (5,6), dextran (7), surfactants like pluronic, polysorbate (8), and influence of pH, temperature, and ionic strength. Although peptides and proteins have high specificity and potency, in many cases, concerns related to the high dose of proteins with varying viscosities as often concentrated formulations with several hundred milligrams per milliliter are required especially to satisfy the limited volume allowed for subcutaneous injection as often preferred by FDA and patients.…”

Section: Introductionmentioning

confidence: 99%

Delivery Considerations of Highly Viscous Polymeric Fluids Mimicking Concentrated Biopharmaceuticals: Assessment of Injectability via Measurement of Total Work Done “WT”

Fassihi

2018

AAPS PharmSciTech

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Abstract.An account is given of the recent development of the highly viscous complex biopharmaceuticals in relation to syringeability and injectability. The specific objective of this study is to establish a convenient method to examine problem of the injectability for the needle-syringe-formulation system when complex formulations with diverse viscosities are used. This work presents the inter-relationship between needle size, syringe volume, viscosity, and injectability of polymeric solutions having typical viscosities encountered in concentrated biologics, by applying a constant probe crosshead speed on the plunger-syringe needle assembly and continuously recording the force-distance profiles. A computerized texture analyzer was used to accurately capture, display, and store force, displacement, and time data. The force-distance curve and area under the curve are determined, and total work done for complete extrusion of the syringe content was calculated automatically by applying an established Matlab program. Various concentrations (i.e., 0.5-4% w/v of polymeric fluids/ dispersions) of polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) with viscosity ranges of 5-100 cP mimicking concentrated monoclonal antibody solutions and complex biopharmaceutical formulations are investigated. Results indicate that calculated values of total work done to completely extrude the syringe content are the most appropriate parameter that describes viscosity-injection force of dispersed formulations. Additionally, the rheological properties of HPMC and PEO fluids in the context of syringeability and injectability are discussed.

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“…PLA, PGA, PLGA or copolymers of e-caprolactone and L,D-lactide or glycolide [88,89] and further poly(ortho esters), polyanhydrides, polyurethanes have been extensively investigated for the preparation of depot formulations by HME. Encapsulation of proteins into PLGA polymers was extensively investigated, showing that lysozyme could be completely recovered from implants in an active form and that complete release could be achieved [90].…”

Section: Biodegradable Water-insoluble Polymersmentioning

confidence: 99%

Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization

Stanković

Frijlink

Hinrichs

2015

Drug Discovery Today

107

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Trehalose Limits BSA Aggregation in Spray-Dried Formulations at High Temperatures: Implications in Preparing Polymer Implants for Long-Term Protein Delivery

Cited by 40 publications

References 38 publications

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Delivery Considerations of Highly Viscous Polymeric Fluids Mimicking Concentrated Biopharmaceuticals: Assessment of Injectability via Measurement of Total Work Done “WT”

Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization

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