Long-Acting Injectable Hormonal Dosage Forms for Contraception

Wu, Liangliang; Janagam, Dileep R.; Mandrell, Timothy D.; Johnson, James R.; Lowe, Timothy J.

doi:10.1007/s11095-015-1686-2

Cited by 37 publications

(48 citation statements)

References 68 publications

(145 reference statements)

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“…Injectable drug suspensions were first approved by the FDA at the end of 1960 in the form of an intramuscular contraceptive injection. Drug release from solid drug particles has been achieved for several months due to the slow dissolution of crystals from the suspension, and crystalline prodrugs can maintain release profiles through a combination of dissolution and parent drug formation rates [53]. …”

Section: Technologies That Have Been Clinically Successful For La mentioning

confidence: 99%

Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy

Owen

Rannard

2016

Advanced Drug Delivery Reviews

117

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Advances in solid drug nanoparticle technologies have resulted in a number of long-acting (LA) formulations with the potential for once monthly or longer administration. Such formulations offer great utility for chronic diseases, particularly when a lack of medication compliance may be detrimental to treatment response. Two such formulations are in clinical development for HIV but the concept of LA delivery has its origins in indications such as schizophrenia and contraception. Many terms have been utilised to describe the LA approach and standardisation would be beneficial. Ultimately, definitions will depend upon specific indications and routes of delivery, but for HIV we propose benchmarks that reflect perceived clinical benefits and available data on patient attitudes. Specifically, we propose dosing intervals of ≥ 1 week, ≥ 1 month or ≥ 6 months, for oral, injectable or implantable strategies, respectively. This review focuses upon the critical importance of potency in achieving the LA outcome for injectable formulations and explores established and emerging technologies that have been employed across indications. Key technological challenges such as the need for consistency and ease of administration for drug combinations, are also discussed. Finally, the review explores the gaps in knowledge regarding the pharmacology of drug release from particulate-based LA injectable suspensions. A number of hypotheses are discussed based upon available data relating to local drug metabolism, active transport systems, the lymphatics, macrophages and patient-specific factors. Greater knowledge of the mechanisms that underpin drug release and protracted exposure will help facilitate further development of this strategy to achieve the promising clinical benefits.

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Section: Technologies That Have Been Clinically Successful For La mentioning

confidence: 99%

Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy

Owen

Rannard

2016

Advanced Drug Delivery Reviews

117

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“…These include non-biodegradable plastics such as polyethylene, polypropylene and PMMA, non-biodegradable elastomers such as silicones and polyurethanes, synthetic bio-degradable polymers such as poly-lactic, poly-glycolic acids and polycaprolactone, naturally derived biodegradable materials such as collagen, gelatin, hyaluronic acid and demineralized bone, and inorganic fillers such as calcium hydroxyapatite and calcium sulfate [60, 85, 86]. Further, excipients and formulation technologies utilized in implantable [88, 89] and parenteral [90, 91] drug delivery dosage forms might be adapted for combination products to modulate an antimicrobial agent’s release profile.…”

Section: Requirements For Local Antimicrobial Delivery Systems Andmentioning

confidence: 99%

Beyond conventional antibiotics — New directions for combination products to combat biofilm

Bayramov

Neff

2017

Advanced Drug Delivery Reviews

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Medical device related infections are a significant and growing source of morbidity and mortality. Biofilm formation is a common feature of medical device infections that is not effectively prevented or treated by systemic antibiotics. Antimicrobial medical device combination products provide a pathway for local delivery of antimicrobial therapeutics with the ability to achieve high local concentrations while minimizing systemic side effects. In this review, we present considerations for the design of local antimicrobial delivery systems, which can be facilitated by modeling local pharmacokinetics in the context of the target device application. In addition to the need for local delivery, a critical barrier to progress in the field is the need to incorporate agents effective against biofilm. This article aims to review key properties of antimicrobial peptides that make them well suited to meet the demands of the next generation of antimicrobial medical devices, including broad spectrum activity, rapid and biocidal mechanisms of action, and efficacy against biofilm.

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“…The results of vaccine studies to-date indicate that a feasible, highly-effective, and durably-protective vaccine will not be available soon (2). At the same time, an increasing body of information has demonstrated the safety and efficacy of long-acting injectable (LAI) medications to treat other conditions (3)(4)(5)(6), and pilot studies have shown durable protection against malaria in mice after intramuscular (IM) drug injection (7,8). Together, these observations prompted the Medicines for Malaria Venture (MMV) to develop the first drug TPP for long-acting injectable chemoprotection (LAI-C) against malaria (9).…”

Section: Introductionmentioning

confidence: 99%

ELQ-331 as a prototype for extremely durable chemoprotection against malaria

Smilkstein

Pou

Krollenbrock

et al. 2019

Preprint

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Background:The potential benefits of long-acting injectable chemoprotection (LAI-C) against malaria have been recently recognized, prompting a call for suitable candidate drugs to help meet this need. On the basis of its known pharmacodynamic and pharmacokinetic profiles after oral dosing, ELQ-331, a prodrug of the parasite mitochondrial electron transport inhibitor ELQ-300, was selected for study of pharmacokinetics and efficacy as LAI-C in mice.Methods: Four trials were conducted in which mice were injected with a single intramuscular dose of ELQ-331 or other ELQ-300 prodrugs in sesame oil with 1.2% benzyl alcohol; the ELQ-300 content of the doses ranged from 2.5 to 30 mg/kg. Initial blood stage challenges with Plasmodium yoelii were used to establish the model, but the definitive study measure of efficacy was outcome after sporozoite challenge with a luciferase-expressing P.yoelii, assessed by whole-body live animal imaging. Snapshot determinations of plasma ELQ-300 concentration ([ELQ-300]) were made after all prodrug injections;after the highest dose of ELQ-331 (equivalent to 30 mg/kg ELQ-300), both [ELQ-331] and [ELQ-300] were measured at a series of timepoints from 6 hours to 5 ½ months after injection.

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Long-Acting Injectable Hormonal Dosage Forms for Contraception

Cited by 37 publications

References 68 publications

Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy

Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy

Beyond conventional antibiotics — New directions for combination products to combat biofilm

ELQ-331 as a prototype for extremely durable chemoprotection against malaria

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