Long-acting injectable formulation technologies: challenges and opportunities for the delivery of fragile molecules

Gonella, Andrea; Grizot, Sylvestre; Liu, Fang; Noriega, Adolfo Lopez; Richard, J.

doi:10.1080/17425247.2022.2105318

Cited by 17 publications

(4 citation statements)

References 128 publications

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“…LA products may be technologically challenging to manufacture, requiring a substantial amount of expertise and experience for successful generic version development [ 43 , 72 , 73 , 74 , 75 , 76 ]. Inherent product characteristics, including complex manufacturing processes, often relying on specialized machinery or infrastructure—especially where LA properties of a formulation depend on niche formulation technologies—may also complicate product development [ 75 , 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Voluntary licensing of long‐acting HIV prevention and treatment regimens: using a proven collaboration‐ and competition‐based mechanism to rapidly expand at‐scale, sustainable, quality‐assured and affordable supplies in LMICs

Gaayeb,

Das,

James

et al. 2023

J Int AIDS Soc.

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Introduction:Emerging long-acting (LA) prevention and treatment medicines, technologies and regimens could be gamechanging for the HIV response, helping reach the ambitious goal of halting the epidemic by 2030. To attain this goal, the rapid expansion of at-scale, sustainable, quality-assured, and affordable supplies of LA HIV prevention and treatment products through accelerated and stronger competition, involving both originator and generic companies, will be essential. To do this, global health stakeholders should take advantage of voluntary licensing of intellectual property (IP) rights, such as through the United Nations-backed, not-for-profit Medicines Patent Pool, as a proven mechanism to support broad access to existing HIV medicines across low-and middle-income countries (LMICs). Discussion: While voluntary licensing may unlock the possibility for generic competition to take place ahead of patent expiry, there are additional elements-of amplified importance for more complex LA HIV medicines-that need to be taken into consideration. This paper discusses 10 enablers of voluntary licensing of IP rights as a model to rapidly expand at-scale, sustainable, quality-assured, and affordable supplies of LA HIV prevention and treatment regimens in LMICs: 1. Identifying promising LA technology platforms and drug formulations at an early developmental stage and engaging with patent holders 2. Consolidating a multidisciplinary network and strengthening early-stage coordination and collaboration to foster innovation 3. Embedding public health considerations in product design and delivery 4. Building innovative partnerships for product development and commercialization 5. Raising awareness of and creating demand for emerging LA products 6. Estimating the market size, ensuring sufficient competition and protecting sustainability 7. Using technology transfer and hands-on technical support to reduce product development timelines and costs 8. Exploring de-risking mechanisms and financial incentives to support generic manufacturers 9. Optimizing strategies for generic product development and regulatory filings 10. Aligning and coordinating efforts of stakeholders across the value chain.Conclusions: Rapid access to emerging LA prevention and treatment regimens and technologies can be facilitated by voluntary licensing-catalyzed and supplemented by enabling collaborative and non-duplicative efforts of various other stakeholders. This can effectively lead to improved-accelerated and cheaper-access to quality-assured medicines for populations in LMICs.

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Section: Discussionmentioning

confidence: 99%

Voluntary licensing of long‐acting HIV prevention and treatment regimens: using a proven collaboration‐ and competition‐based mechanism to rapidly expand at‐scale, sustainable, quality‐assured and affordable supplies in LMICs

Gaayeb,

Das,

James

et al. 2023

J Int AIDS Soc.

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“…PLGA is the most commonly used polymer in long-acting injections because of its safety profile, biocompatibility, and biodegradability. It has been successfully used in commercial products for non-vaccine-controlled release applications such as Lupron®, Trelstar®, Bydureon®, Signifor® LAR, Sandostatin® LAR, Somatuline® Depot for more than 30 years [ 21 ]. Furthermore, PLGA is a synthetic polymer allowing tuning of the release profile by changing its characteristics such as the molecular weight, lactic/glycolic acid ratio or polymer end chemistries [ 22 ].…”

Section: Formulation Challenges Of Sav Technologiesmentioning

confidence: 99%

Single administration vaccines: delivery challenges, in vivo performance, and translational considerations

Michaelides,

Prasanna,

Badhan

et al. 2023

Expert Review of Vaccines

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Introduction With a limited global supply of vaccines and an increasing vaccine hesitancy, improving vaccination coverage has become a priority. Current vaccination regimes require multiple doses to be administered in a defined schedule where missed doses may lead to incomplete vaccine coverage and failure of immunization programmes. As such, there is an ever-increasing demand to convert multi-dose injectable vaccines into single-dose formats, often called single administration vaccines (SAVs). Areas covered This review summarizes recent developments in the field of SAVs, with a focus on pulsatile or controlled-release formulations. It will identify the technical challenges, translational as well as commercial barriers to SAVs development. Furthermore, the progress of SAV formulations for hepatitis B and polio vaccines will be reviewed thoroughly as case studies, with a focus on the development challenges and the preclinical immunogenicity/reactogenicity data. Expert opinion Despite the efforts to develop SAVs, few attempts have advanced to Phase-I trials. Considering the SAV development journey and bottlenecks, including commercial barriers from the early stages, may overcome some of the hurdles around the technology. The renewed global focus on vaccines since the COVID-19 pandemic could facilitate development of a new generation of technologies for pandemic preparedness including strategies for SAVs.

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Section: Introductionmentioning

confidence: 99%

“…Long-acting injectable (LAI) formulations are parenteral delivery systems that provide a sustained release and thereby a steady exposure to APIs intended to be delivered for prolonged periods that range from days to months, in contrast to oral formulations [ 1 , 2 , 3 , 4 ]. LAI formulations improve quality of life and patient compliance by substantially minimizing administration frequency as well as undesired side effects [ 1 , 4 , 5 ]. 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 ].…”

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

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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.

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Long-acting injectable formulation technologies: challenges and opportunities for the delivery of fragile molecules

Cited by 17 publications

References 128 publications

Voluntary licensing of long‐acting HIV prevention and treatment regimens: using a proven collaboration‐ and competition‐based mechanism to rapidly expand at‐scale, sustainable, quality‐assured and affordable supplies in LMICs

Voluntary licensing of long‐acting HIV prevention and treatment regimens: using a proven collaboration‐ and competition‐based mechanism to rapidly expand at‐scale, sustainable, quality‐assured and affordable supplies in LMICs

Single administration vaccines: delivery challenges, in vivo performance, and translational considerations

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

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