Page 24 - 2018

Ph.D.
(Pharmacy)
DESIGN AND DEVELOPMENT OF LONG ACTING INJECTABLE
MICROSPHERES OF OCTREOTIDE ACETATE AND NALTREXONE

Ph.D. Scholar : Patel Bhaveshkumar Vallabhbhai
Research Supervisor : Dr. R. P. Patel

Regi. No.: 11146021004
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
(Sandostatin LAR) in Animal Pharmacokinetic Study using Rat model. The in-vitro and in-
vivo data clearly indicated that the developed product was suitable as long actting
injectable depot product.

Keywords: Octreotide, Microsphere, Process, Drug Entrapment, Bio-degradable, Solvent
Evaporation

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