Research Article FORMULATION AND EVALUATION OF OCTREOTIDE ACETATE LOADED PLGA MICROSPHERES L. MARY SONY PHILO 1 , SUMIT SHAH 2 , A.V BADARINATH 1 , C.GOPINATH 1 1 Annamacharya college of pharmacy, Rajampet, Kadapa, 2 Celon Laboratories Limited, Hyderabad, Andhra Pradesh, India. Email: Sonyphilo5@gmail.Com Received: 15 Jun 2013, Revised and Accepted: 09 Jul 2013 ABSTRACT Objective: The objective of the present work was to formulate and evaluate controlled release Octreotide acetate microspheres for subcutaneous administration for treating symptoms associated with metastatic carcinoid and vasoactive intestinal peptide tumors (VIP- secreting tumors) and acromegaly effectively and also to improve patient compliance with fewer side effects. Octreotide is a long acting cyclic octapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin. It inhibits growth hormone, glucagon, and leutinizing hormone response to Gonadotropin releasing hormone, serotonin gastrin, vasoactive intestinal peptide, motilin and pancreatic polypeptide. Method: Different formulations were prepared by following solvent evaporation technique (double emulsion) using biodegradable poly (Lactide-co- Glycolide) acid and evaluated for percentage yield, entrapment efficiency, surface morphology (SEM), particle size analysis, in-vitro drug release and stability studies. Results: The prepared microspheres were white, free flowing and spherical in shape. The mean Particle size of the microspheres was found in the range of 26 to 206μm. The drug-loaded microspheres showed 70-86% of entrapment and release was extended up to 6 to 8 h releasing 93% of the total drug from the microspheres. The infrared spectra showed stable character of octreotide in the drug-loaded microspheres and revealed the absence of drug-polymer interactions. Scanning electron microscopy study revealed that the microspheres were spherical and porous in nature. Conclusion: The octreotide is uniformly distributed within the microspheres which are made of a biodegradable D,L-lactic and glycolic acids copolymer. The optimized formulations of Octreotide acetate microspheres with controlled release were attempted for a release upto atleast one month. Keywords: Bioavailability, Controlled release, Microspheres, Octreotide acetate, PLGA polymer, SEM, Subcutaneous. INTRODUCTION Many proteins currently being developed are aimed at chronic conditions where therapy may be required over months or years. Alternative administration by frequent injections to keep the protein drug at effective concentrations is tedious, expensive, and has poor patient compliance. Therefore, development of sustained release injectable dosage forms becomes necessary to improve the efficacy of peptide drugs and eliminate the need for frequent administration [1]. Octreotide is a long acting cyclic octapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin. It inhibits GH, glucagon, LH response to GnRH ,serotonin gastrin, vasoactive intestinal peptide ,motilin and pancreatic polypeptide. Octreotide is used to treat the symptoms associated with metastatic carcinoid and vasoactive intestinal peptide tumors (VIP-secreting tumors). Octreotide normalizes the growth hormone levels in acromegaly patients. The goal of treatment in acromegaly is to reduce GH and IGF levels to normal. Octreotide can be used in patients who had an inadequate response to surgery or in those for whom surgical resection is not an option. It may also be used in patients who have received radiation and have had an inadequate therapeutic response. Marketed formulation of octreotide is available as Sandostatin ® LAR Depot (octreotide acetate for injectable suspension) which is a somatostatin analogue. Its effects in the body are similar to those of the naturally occurring hormone, except that Sandostatin ® LAR Depot remains active much longer than somatostatin.Sandostatin ® LAR Depot binds to the somatostatin receptors, and thereby suppresses the release of the peptides and amines from the tumor and inhibits their action, suppressing the severe diarrhoea and flushing associated with this disease. Rapid gastrointestinal (GI) transit leads to accumulation of fluid in the colon and profuse volumes of watery stool Sandostatin ® slows GI transit and increases fluid absorption by over 300%. The aim of the present research was to formulate and evaluate octreotide acetate microspheres for subcutaneous administration for period on one month controlled release delivery system. Biodegradable microspheres were shown to improve the bioavailability of peptides by protecting them from physical degradation and proteolysis in body fluids. Poly (D,L-lactide) (PLA) and poly (D,L-lactide-co-glycolide) (PLGA) are the most widely used and well-characterized materials for the preparation of biodegradable microspheres. MATERIALS AND METHODS Materials Octreotide acetate was purchased from Hemmo pharmaceutical PVD (Mumbai). Poly (D, L-Lactic-co-glycolic acid) 50:50 (PLGA 50:50) Resomer®RG 504 and Resomer®RG 504H were supplied by Evonik/Boehringer-Ingelheim (Germany). Poly (vinyl alcohol) (PVA) (MW 22000, 88% hydrolyzed) and ethyl acetate were supplied by Merck (India). Dichloromethane, Tween 80, Sodium chloride, Potassium chloride, di-sodium hydrogen phosphate, Potassium dehydrogenate phosphate and sodium azide were obtained from J. T. Baker (India). Preparation of octreotide acetate microspheres Octreotide acetate-loaded microspheres were prepared by a double emulsion-solvent evaporation technique. Briefly, 500 mg PLGA 5050 was dissolved in 5 mL dichloromethane (oil phase). An aqueous solution containing 50 mg of octreotide acetate in 1 ml of phosphate buffer pH 7.4 was prepared separately (inner aqueous phase or W1). The first aqueous (W1) phase was emulsified into the oil phase (containing PLGA), using a high-speed homogenizer (T18 basic, IKA, Germany) at 2-8 °C using different speeds and time durations to form water in oil primary emulsion. This primary emulsion was added in to 100 ml of external aqueous phase containing 1 % PVA solution to form secondary emulsion at 6000 rpm speed for 3 mins at 2-8°C International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 5, Suppl 3, 2013 A A c c a a d d e e m mi i c c S Sc c i i e e n n c c e e s s