Design and development of long acting injectable microspheres of octreotide acetate and naltrexone

Abstract

Development of long acting injectable microsphere based formulation specially for a peptide molecule (i.e. octreotide acetate) with a very short half life, which are intended for chronic therapy for longer duration, have become more popular in few recent past decades. In this investigation, the use of biodegradable polymers for microencapsulation of octreotide acetate using different manufacturing techniques is investigated. The use of different process options and variables to prepare octreotide acetate microspheres is also studied. Octreotide acetate microspheres using bio-degradable poly(D,L-lactide-co-glycolide) prepared using solvent-evaporation technique had significantly less drug entrapment. Different process variables were tried to increase the drug entrapment of microspheres as solvent evaporation technique is the most preferred technique to have smooth scale up and commercialization. When w/o/w solvent evaporation technique was used, it faced issue of very low drug entrapment. Though few relevant process variables were changed, but still the issue of low drug entrapment was not completely resolved. Hence, a novel process using o/o solvent extraction process was tried and the issue of low drug entrapment was resolved. The microspheres obtained from final and optimized process were subjected to thorough characterization. All the relevant analytical technique used for characterization were appropriately developed before being used for characterization. Few lots of already commercialized internation brand (i.e. SANDOSTATING LAR) were fully characterized using well developed and optimized analytical methods. Few batches prepared using final optimized microsphere manufacturing process were fully characterized to understand the comparative in-vitro behaviour against internation brand product. The final batch was also subjected to stability conditions as per ICH requirements and all critical attributes were characterized on stability. The in vivo behaviour was also checked in comparison to reference product (S