Current State and Opportunities with Long-acting Injectables: Industry Perspectives from the Innovation and Quality Consortium “Long-Acting Injectables” Working Group

Bauer, Andrea; Berben, Philippe; Chakravarthi, Sudhir S.; Chattorraj, Sayantan; Garg, Ashish; Gourdon, Betty; Heimbach, Tycho; Huang, Ye; Morrison, Christopher D.; Mundhra, Deepak; Palaparthy, Ramesh; Saha, Pratik; Siemons, Maxime; Shaik, Naveed A; Shi, Yi; Shum, Sara; Thakral, Naveen K.; Urva, Shweta; Vargo, Ryan; Koganti, Venkat R.; Barrett, Stephanie E.

doi:10.1007/s11095-022-03391-y

Cited by 14 publications

(18 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, Model B (Equation ( 5)) was fitted in JMP in this way with reasonable guesses for each parameter as starting points. The reverse-transformed Equation (5), with reference values substituted following Equation (9), would be as shown in Equation (10).…”

Section: Reversing the Transformmentioning

confidence: 99%

“…The term Kt j in the above equation was derived as an Arrhenius equation in Section 3.2.2, but in the interest of brevity, this substitution is not shown explicitly. In our studies, we fitted Equation (10) directly to the data from our case studies, solving for the product-specific terms A j , B j , N j , x j,inf and the temperature term K2 j for each size quantile and the nonlinear exponents (N 1 − N 4 ) on ω, BL, D b , and ρ b , which were shown to be consistent in value across all studies and thus product independent, as will be illustrated in Sections 4.1 and 4.2. We note that not all power-law exponents can be estimated in every case study, as the relevant process parameter might not have been investigated in the experimental design, in which case the associated exponents were fixed to those in Equation ( 6) (Model C).…”

Section: Reversing the Transformmentioning

confidence: 99%

See 1 more Smart Citation

Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

Clancy,

Guner,

Chattoraj

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

This study aimed to develop a practical semi-mechanistic modeling framework to predict particle size evolution during wet bead milling of pharmaceutical nanosuspensions over a wide range of process conditions and milling scales. The model incorporates process parameters, formulation parameters, and equipment-specific parameters such as rotor speed, bead type, bead size, bead loading, active pharmaceutical ingredient (API) mass, temperature, API loading, maximum bead volume, blade diameter, distance between blade and wall, and an efficiency parameter. The characteristic particle size quantiles, i.e., x10, x50, and x90, were transformed to obtain a linear relationship with time, while the general functional form of the apparent breakage rate constant of this relationship was derived based on three models with different complexity levels. Model A, the most complex and general model, was derived directly from microhydrodynamics. Model B is a simpler model based on a power-law function of process parameters. Model C is the simplest model, which is the pre-calibrated version of Model B based on data collected from different mills across scales, formulations, and drug products. Being simple and computationally convenient, Model C is expected to reduce the amount of experimentation needed to develop and optimize the wet bead milling process and streamline scale-up and/or scale-out.

show abstract

Section: Reversing the Transformmentioning

confidence: 99%

Section: Reversing the Transformmentioning

confidence: 99%

Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

Clancy,

Guner,

Chattoraj

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…For this reason, LAIs can provide huge benefits for patients suffering from dysphagia or chronic diseases, such as mental disorders, HIV infection, tuberculosis, and hormone replacement treatments, where limited patient adherence may have a negative outcome on treatment efficacy [ 6 , 7 , 8 , 9 ]. LAIs are primarily delivered through the intramuscular (IM) or subcutaneous (SC) routes as oil solutions, in situ forming gels, microspheres, implants, or micro- or nanosuspensions [ 3 , 10 , 11 ]. Owing to concerns over side effects, patient tolerance, and pain upon injection in most of the delivery systems, the micro- and nanosuspension technology has significantly advanced, and many of the more recent approved LAIs are either nano- or microsuspensions [ 4 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting Injectable Formulations

Nandi,

Verstrepen,

Hugo Silva

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

A bottom-up approach was investigated to produce long-acting injectable (LAI) suspension-based formulations to overcome specific limitations of top-down manufacturing methods by tailoring drug characteristics while making the methods more sustainable and cost-efficient. A Secoya microfluidic crystallization technology-based continuous liquid antisolvent crystallization (SCT-CLASC) process was optimized and afterward compared to an earlier developed microchannel reactor-based continuous liquid antisolvent crystallization (MCR-CLASC) setup, using itraconazole (ITZ) as the model drug. After operating parameter optimization and downstream processing (i.e., concentrating the suspensions), stable microsuspensions were generated with a final solid loading of 300 mg ITZ/g suspension. The optimized post-precipitation feed suspension consisted of 40 mg ITZ/g suspension with a drug-to-excipient ratio of 53:1. Compared to the MCR-CLASC setup, where the post-precipitation feed suspensions contained 10 mg ITZ/g suspension and had a drug-to-excipient ratio of 2:1, a higher drug concentration and lower excipient use were successfully achieved to produce LAI microsuspensions using the SCT-CLASC setup. To ensure stability during drug crystallization and storage, the suspensions’ quality was monitored for particle size distribution (PSD), solid-state form, and particle morphology. The PSD of the ITZ crystals in suspension was maintained within the target range of 1–10 µm, while the crystals displayed an elongated plate-shaped morphology and the solid state was confirmed to be form I, which is the most thermodynamically stable form of ITZ. In conclusion, this work lays the foundation for the SCT-CLASC process as an energy-efficient, robust, and reproducible bottom-up approach for the manufacture of LAI microsuspensions using ITZ at an industrial scale.

show abstract

“…Long-acting injectable (LAI) formulations represent a means for achieving sustained drug release to enable less frequent dosing. − The most common LAI formulation strategies are biodegradable/biocompatible polymeric or oil-based formulations or crystalline drug suspensions. However, these strategies suffer from either the inability to handle high drug load as would be required for monthly or less frequent dosing of ASOs where weekly/monthly doses are in the order of 100s of milligrams ,, or are suitable only for poorly soluble drugs.…”

Section: Introductionmentioning

confidence: 99%

Injectable Biodegradable Silica Depot for Controlled Subcutaneous Delivery of Antisense Oligonucleotides with beyond Monthly Administration

McGowan,

Gennemark,

Akieh-Pirkanniemi

et al. 2023

Mol. Pharmaceutics

View full text Add to dashboard Cite

Current State and Opportunities with Long-acting Injectables: Industry Perspectives from the Innovation and Quality Consortium “Long-Acting Injectables” Working Group

Cited by 14 publications

References 112 publications

Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting Injectable Formulations

Injectable Biodegradable Silica Depot for Controlled Subcutaneous Delivery of Antisense Oligonucleotides with beyond Monthly Administration

Contact Info

Product

Resources

About