Lipid based intramuscular long-acting injectables: Current state of the art

Wilkinson, Janine M.; Ajulo, Damilola; Tamburrini, Valeria; Gall, Gwénaëlle Le; Kimpe, Kristof; Holm, René; Belton, Peter; Qi, Sheng

doi:10.1016/j.ejps.2022.106253

Cited by 31 publications

(16 citation statements)

References 133 publications

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“…The lipophilic OD‐based parenteral LA system has been clinically employed for diverse diseases, especially schizophrenia and hormone replacement therapy 2,27 . Compared with other parenteral depot principles, OD system has a simple manufacturing process and an excellent long‐term storage stability, preventing the oxidation or hydrolysis of active compounds.…”

Section: Resultsmentioning

confidence: 99%

“…The lipophilic OD-based parenteral LA system has been clinically employed for diverse diseases, especially schizophrenia and hormone replacement therapy. 2,27 Compared with other parenteral depot principles, OD system has a simple manufacturing process and an excellent long-term storage stability, preventing the oxidation or hydrolysis of active compounds. Moreover, an extended duration of action is achieved by employing a suitable lipophilic vehicle possessing high affinity to drug candidates, retarding the transfer of lipophilic prodrugs into the interstitial fluid surrounding the injection site.…”

Section: Preparation and Characterization Of Ev-p Od Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Parenteral long‐acting (LA) delivery systems have been increasingly explored to provide steady therapeutic exposure for long periods of time (weeks to months) following a single injection, thereby improving patient compliance 1,2 . Several pharmaceutical approaches have been constructed to formulate LA systems, including polymer‐ or lipid‐based particulates, drug suspensions, in situ forming‐gel and oil depots (OD) 2–5 . In these LA injectable systems of chemicals, therapeutic agents principally remain at the injection site with the help of polymer‐ or lipid‐based physical barriers or due to the intrinsically low solubility at the injection site, exhibiting continuous drug dissolution, partition, and subsequent absorption into the bloodstream 1,4,6 .…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Several pharmaceutical approaches have been constructed to formulate LA systems, including polymeror lipid-based particulates, drug suspensions, in situ forming-gel and oil depots (OD). [2][3][4][5] In these LA injectable systems of chemicals, therapeutic agents principally remain at the injection site with the help of polymer-or lipid-based physical barriers or due to the intrinsically low solubility at the injection site, exhibiting continuous drug dissolution, partition, and subsequent absorption into the bloodstream. 1,4,6 The OD system is principally a liquidstate formula, in which a lipophilic (pro)drug is dissolved in a lipophilic oily vehicle.…”

Section: Introductionmentioning

confidence: 99%

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Exploration of lipidic prodrug‐loaded oil depot system for intramuscular prolonged delivery of entecavir

Jeong

Choi

et al. 2023

Bulletin Korean Chem Soc

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Entecavir (EV) is a first‐line antiretroviral agent to treat chronic hepatitis B. However, its oral administration is challenging, due to food effect on intestinal absorption. Therefore, in order to afford improved patient's compliance, a novel long‐acting injectable oil depot (OD) system of entecavir‐3‐palmiate (EV‐P), a lipidic ester prodrug of EV, was formulated. The OD consisted of oleic acid and benzyl alcohol as oily vehicles, with a suitable viscosity (38.6 centipoise with shear rate of 1 s−1). The prodrug was gradually released from the OD under sink conditions, providing delayed liberation than that by the hydrophilic parent compound. Following the intramuscular injection in rats, EV‐P OD provided a markedly protracted EV profile compared to oral EV; the EV levels in plasma were expanded over 2 weeks, with elimination half‐life of about 7 days. Therefore, we concluded that EV‐P OD can be a promising approach for a prolonged delivery of EV.

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Section: Resultsmentioning

confidence: 99%

Section: Preparation and Characterization Of Ev-p Od Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Exploration of lipidic prodrug‐loaded oil depot system for intramuscular prolonged delivery of entecavir

Jeong

Choi

et al. 2023

Bulletin Korean Chem Soc

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Tricaprylin‐based drug crystalline suspension for intramuscular long‐acting delivery of entecavir with alleviated local inflammation

Jeong,

Ho,

Park

et al. 2024

Bioengineering & Transla Med

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In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin‐based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3‐palmitate (EV‐P), an ester lipidic prodrug for entecavir (EV), was employed. The EV‐P‐loaded TS was prepared by ultra‐sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 μm), crystallinity (melting point of 160–165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS‐injected site, drug aggregates of up to 500 μm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS‐injected site, with >4 weeks remaining of the oily vehicle in micro‐computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long‐acting delivery, with improved local tolerability.

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Biodegradable Long-Acting Injectables: Platform Technology and Industrial Challenges

Duvnjak

Villois

Ramazani

2023

Handbook of Experimental Pharmacology

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Lipid based intramuscular long-acting injectables: Current state of the art

Cited by 31 publications

References 133 publications

Exploration of lipidic prodrug‐loaded oil depot system for intramuscular prolonged delivery of entecavir

Exploration of lipidic prodrug‐loaded oil depot system for intramuscular prolonged delivery of entecavir

Tricaprylin‐based drug crystalline suspension for intramuscular long‐acting delivery of entecavir with alleviated local inflammation

Biodegradable Long-Acting Injectables: Platform Technology and Industrial Challenges

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