The aim of our presentation is introducing - PDF document

1 The aim of our presentation is introduci
The aim of our presentation is introducing BEPO®, a long - acting injectable proprietary technology that forms a bioresorbable polymeric depot once administered in the body. BEPO® belongs to in situ forming depot technology (ISFD) whereby a solvent - exchange process is the mediating mechanism that elicit s the precipitation of the polymer leading to the formation of a drug releasing matrix in situ . The concept of solvent - removal in s itu polymer precipitation was first introduced by Dunn et al. in 1990 (1) and subsequent developments that led to approved drug products (ie Atridox, Eligard, S ublocade TM ) were based on the utilization of either poly(D,L - Lactide) (PLA) or PLGA random copol ymers (Jain et al . (2)) . Except PLGA - PEG - PLGA Triblock copolymers which have been clinically used in the thermosensitive hydrogel forming platform Regel (Elstad et al. (3)) developed by MacroMed, no depot - forming controlled drug delivery system based on th e utilization of PEG - Polyester block copolymers has been approved in drug products. BEPO® 's core components comprise a mixture of two block copolymers , a triblock and a diblock, made of Polyethylene glycol (PEG) and Poly(D,L - Lactid e ) (PLA), a biocompatib le solvent whose role is to dissolve the copolymers , and a Pharmaceutically A ctive Ingredient (API) that can be either solubilized (solution) or dispersed (suspension). As functional excipients, t he copolymers are amphiphilic due to the presence of a hydrophilic block (PEG) and a hydrophobic block (PLA). They are designed to be essentially non - aqueous soluble and precipitate upon contact with aqueous fluids . In addition to introducing the scientific elements req uired to the understanding of our drug delivery platform, we also present two case studies aiming at exemplifying why and how BEPO® is bringing the

2 required flexibility to formulate a wid
required flexibility to formulate a wide variety of APIs and adress various unmet medical needs. When comes into consideration the systemic delivery of a drug, our long - acting formulations can be injected subcutaneously. Designing the optimal release profile requires an in - depth understanding of how input parameters do affect the rate and duration of release of a drug. O ne of the critical step with in - situ forming depot technology lies in the phase inversion dynamic that takes place upon the solvent exchange process leading to the precipitation of the polymer (4) . Our data have shown how the modulation of the pol ymeric composition has a significant impact on the solvent exchange rate between the organic solvent and the surrounding aqueous medium which subsequently determines the microstructure of the resulting depot s . This has been demonstrated studying the in vit ro release of two model molecules: bupivacaine and ivermectin . The other case study will show how BEPO® can be used to locally deliver a drug in the intra - articular space. The local delivery of a drug is another technological aspect that makes our technolo gy versatile. We will present data showing how the polymeric composition has gu ided the choice of a lead formulation exhibiting desired release profile of Celecoxib, an NSAID drug, but also desired mechanical characteristics to make the depot morcellizable (5) . In vitro and in vivo data will be presented to exemplify this case . List of References: (1) Dunn R. L . , US Patent 4,938,763 (1990) (2) Jain et al., Adv Drug Deliv Rev 107 (2016) 213 – 227 (3) Alstad et al. , Adv Drug Deliv Rev. 2009 Aug 10;61(10):785 - 94 (4) Parent et al., J Control Release. 2013 Nov 28;172(1):292 - 304 (5) Hurtig et al., Osteoarthritis and Cartilage, April 2016 Volume 24, Supplement 1, Pages S524 – S52