In Vitro Drug Release Testing and In Vivo/In Vitro Correlation for Long Acting Implants and Injections

Abstract

An advantage of long acting implants and injections is their ability to maintain a relatively constant drug concentration at the site of interest. In vitro drug release testing, particularly where an in vivo / in vitro relationship has been established, can help in ensuring in vivo performance. There are various in vitro release testing methods, which are chosen, based on availability, dosage form specifi cations and drug properties. These are categorized into three groups: sample and separate, fl ow-through and dialysis. Although there are currently no standard methods for in vitro release testing of controlled release parenterals, standard dissolution apparatus specifi ed by the United States Pharmacopeia have been adapted in some cases and the development of compendial monographs is anticipated. An in vivo / in vitro correlation can predict the bioavailability characteristics of a product based on release in vitro .

Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics

“…The standard drug solution achieved 81.30%±4.22% of drug release within 8 h, followed by a slower release till it reached a total drug release of ~98.20%±3.51% within 24 h. At this point, the drug had reached the steady-state equilibrium in which no significant increase in the rate of cefuroxime released into the tested medium after 36 h. CLN had a similar release profile as the drug solution but at a slower rate as compared to the standard solution and achieved maximum drug release 87.50%±4.22% after 36 h. CLN presented 80% release of drug, the generally acceptable value in the dosage form that should be released from a long-term drug delivery system. 45 The CLN release curve showed a rapid initial burst (from the small droplets' size) and an extended tail (from larger droplets) that may be attributed to its PDI. 44 This result was supported by Ritger and Peppas (1987) 46 who demonstrated the effect of PDI (particle size distribution) on drug release behavior.…”

In vitro dissolution testing strategies for nanoparticulate drug delivery systems: recent developments and challenges

“…In order to ensure product performance and assist in product development, extensive efforts have been made to develop suitable in vitro dissolution/release testing methods for nanoparticulate delivery systems (13–16). These methods can be broadly divided into three categories: i) membrane diffusion methods (such as the dialysis methods); ii) sample and separation methods; and iii) continuous flow methods.…”

Analytical Techniques for the Characterization of Bioactive Coatings for Orthopaedic Implants

“…In addition, they reduce the experimental time, lower expenses, and are undoubtedly more ethical. Much research effort has been invested into the development of appropriate in vitro release testing methods and technologies to ensure simplicity, batch-to-batch reproducibility, and comparability with real in vivo body conditions [ 202 , 203 ]. In this regard, a variety of methods have been developed for in vitro drug release testing, generally involving the immersion of the carrier containing the selected drug in the prepared dissolution media, such as SBF, under well-defined conditions.…”

“…This step is followed by sampling at different time intervals, supplying fresh dissolution media, the filtration/centrifugation of the sample taken [ 204 ], and drug detection in the sample using UV-Vis spectroscopy [ 108 ], enzyme-linked immunosorbent assay (ELISA) [ 40 ], or high-performance liquid chromatography (HPLC) [ 92 ]. Seven variants of United States Pharmacopeia (USP) apparatuses [ 202 ] (USP apparatus type I is shown on Figure 5 ) or other designs (e.g., Franz diffusion cells) are currently the most frequently used for in vitro drug release testing [ 57 , 203 ].…”