Formulation and pharmacology of long-acting rilpivirine

Williams, Peter; Crauwels, Herta; Basstanie, Esther D.

doi:10.1097/coh.0000000000000164

Cited by 74 publications

(43 citation statements)

References 23 publications

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“…However, the development of mechanical attrition processes [64] (for example nanomilling technologies and high pressure homogenisation) and non-attrition nanoparticle fabrication (for example emulsion-templated freeze drying) has allowed access to nano-scale solid drug particles (< 1 μm) [65-68]. The rilpivirine LA and cabotegravir LA options [6, 7] that are in extended clinical trials (including evaluation of simultaneous combination in LATTE 2) are based upon this technology.…”

Section: Emerging Technologies For La Formulationmentioning

confidence: 99%

“…The first of these, developed by Janssen is rilpivirine LA (Edurant ® ) [4-6] and the second, developed by ViiV Healthcare is cabotegravir LA [7, 8]. Both of these medicines are based upon the same nanotechnology that generates solid drug nanoparticle (SDN) suspensions via the process of wet bead milling (also known as nanomilling; see also section 4.1. below).…”

Section: Introductionmentioning

confidence: 99%

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

Owen

Rannard

2016

Advanced Drug Delivery Reviews

123

102

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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: Emerging Technologies For La Formulationmentioning

confidence: 99%

Section: Introductionmentioning

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

123

102

View full text Add to dashboard Cite

show abstract

“…Indeed, the exciting new developments for HIV prevention and therapy have involved the formation of SDNs of rilpivirine and cabotegravir, by the process of wet-bead milling. 19,20 These formulations are spearheading the advent of LA injectables for infectious diseases, and provide between 1 month and 3 months of therapeutic exposure from a single intramuscular depot. The two-drug combination of injectable long-acting cabotegravir with rilpivirine every 4 weeks or every 8 weeks was recently shown to be as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated.…”

Section: Introductionmentioning

confidence: 99%

Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges

Swindells

Siccardi

Barrett

et al. 2018

int j tuberc lung dis

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SUMMARY Long-acting/extended release drug formulations have proved very successful in diverse areas of medicine including contraception, psychiatry, and most recently, HIV disease. While challenging, application of this technology to TB treatment could have substantial impact. The length of treatment required for all forms of TB put existing regimens at risk for failure because of early discontinuations and treatment default. Long-acting injections, for example administered monthly, could improve patient adherence and treatment outcomes. We review the state of the science for potential long-acting formulations of existing TB drugs, and propose a Target Product Profile for new formulations to treat latent TB infection. The physicochemical properties of some TB drugs make them unsuitable for long-acting formulation, but there are promising candidates that have been identified through modeling and simulation, and other novel agents and formulations in preclinical testing. An efficacious long-acting treatment for latent TB infection, particularly for those co-infected with HIV, and if coupled with a biomarker to target those at highest risk for disease progression, would be an important tool to accelerate progress towards TB elimination.

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“…The use of nanoparticles (NPs) for drug delivery systems is an expanding area of research (Vadakkan et al 2013;Pedrosa et al 2014;Choudhary and Kusum Devi 2015;Patel et al 2013). The antimicrobial properties of some NPs are well documented (Donnellan immunodeficiency virus (HIV) (Mcdonald et al 2014;Williams et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Intracellular delivery of nano‐formulated antituberculosis drugs enhances bactericidal activity

Donnellan

Stone

Johnston

et al. 2017

J of Interdiscip Nanomed

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Tuberculosis kills more people worldwide than any other infectious disease. Treatment requires multiple drug therapy administered over long periods (6-24 months). The emergence of multidrug-resistant strains is a major problem, and with few new drugs in the pipeline, a novel modus operandi is urgently required. Solid drug nanoparticles (SDNs), a new development in nanomedicine, offer a fresh therapeutic approach. Here, we show that SDNs are more effective (50-fold) at killing pathogenic mycobacteria than aqueous forms of the same drug and can target mycobacteria internalised by macrophages, where bacilli reside. We demonstrate synthesis of dual and triple drug loaded SDNs, facilitating combination tuberculosis therapy. Our results suggest that by employing SDNs of existing antibiotics, it may be possible to improve drug delivery and therefore reduce drug dosage to lessen side effects and fight drug resistance.

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Formulation and pharmacology of long-acting rilpivirine

Abstract: By building on expertise with long-acting injectable antipsychotic agents, RPV has been formulated as an agent for infrequent intramuscular dosing, in addition to its conventional oral tablet forms. The advantages of adherence to a regimen of intermittent injections may be significant.

Cited by 74 publications

References 23 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

Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges

Intracellular delivery of nano‐formulated antituberculosis drugs enhances bactericidal activity

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