An Introduction to Long Acting Injections and Implants

Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot

“…2 However, some time-drug plasma concentration profiles in published articles indicate an obvious burst release in the initial stages, while sustained but low steady plasma levels of drug have been observed at later stages. [16][17][18] In some cases, a small burst release is appropriate for the effect of the drug by rapidly reaching the effective drug concentration; however, an obvious burst release might trigger drug toxicity.…”

“…Currently, there are two main strategies by which hydrophilic macromolecular drugs can be made long-acting, ie, by extending drug release using sustained-release delivery systems or by improving the retention of the drug in plasma by modifying the drug chemically. 2 For the first strategy, in situ-forming systems (ISFS), especially poly( D,L -lactideco-glycolide) copolymer (PLGA) depots, which can be injected as a low viscous …”

“…They are based on biodegradable polymers with excellent biocompatibility, are approved for parenteral administration, can be easily modulated, and cover a wide range of release periods. [1][2][3] So far, there are two commercialized products (Eligard ® and Atridox ® ), both of which use N-methyl-2-pyrrolidone (NMP) as the solvent and polylactic acid or PLGA as the biodegradable, biocompatible, and water-insoluble matrix. For the second strategy, PEGylation, the process of covalent attachment of one or more polyethylene glycol (PEG) polymer chains to a therapeutic molecule, is now established as the method of choice for improving the pharmacokinetics and pharmacodynamics of parenteral agents.…”

“…PEG and its conjugates are cleared from the body mainly by the kidney, and the excretion rate has a sigmoidal relationship with the molecular weight of the polymer, showing a greatly reduced rate over approximately 40 kDa. 2 PEGs with a high molecular weight are eliminated slowly via the liver or become permanently entrapped into tissues or cells. Our previous studies indicated that, with proper design, PEGylated ROP that is both bioactive and long circulating in the blood could be obtained.…”

Comparison of the Local Tolerability to 5 Long-acting Drug Nanosuspensions with Different Stabilizing Excipients, Following a Single Intramuscular Administration in the Rat

“…Long-acting injectable (LAI) or implantable drug delivery systems are able to release a drug in a controlled manner, hence, enabling effective drug plasma concentrations and exposure at the site(s) of pharmacologic activity to be maintained for long periods of time (i.e., up to several months) following a single administration (Burgess and Wright 2012). The steady plasma concentrations that are achieved can benefit the clinical outcome through a variety of principles, including an improved treatment adherence, less frequent disease relapses, a potential lowered risk of therapy resistance development, lower equivalent daily doses and lower peak plasma concentrations and, therefore, potentially reduced frequency and/or severity of treatment-related adverse events.…”