1. Development and Assessment of Captopril Loaded Matrix-Type Pellets Roderick B. Walker 1, Sandile M.M. Khamanga and Samantha Y. Mukozhiwa Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa 1 Corresponding author: R.B.Walker@ru.ac.za CPT pellets with acceptable morphological and physicochemical characteristics were successfully manufactured using MCC, HPC and distilled water (Fig 1B). Formulations containing up to 20% w/w EC produced pellets with acceptable physicochemical characteristics. CPT content studies showed that the pellets typically ranged in content between approximately 88-101%. In vitro CPT release studies revealed that CPT was rapidly released from all matrix-type pellet formulations and CPT was released virtually in totality within 2 hours (Fig 2). Presented at the 41 st Annual Meeting & Exposition of the Controlled Release Society, July 13-16, 2014, Chicago, U.S.A. Introduction The use of multiparticulate drug delivery systems (MDDS) has been extensively studied in an effort to enhance the clinical benefits of well known compounds [1-5]. The quality and physicochemical characteristics of pellets manufactured by extrusion-spheronization are influenced by several factors including formulation composition and process parameters [6,7]. Objectives To manufacture CPT loaded matrix-type pellets using extrusion-spheronization. To determine the effects of formulation variables on the physicochemical properties of pellets and their formation. Experimental CPT pellets were manufactured using Caleva ® extrusion- spheronization equipment (Sturminster Newton, United Kingdom). All pellet formulations were manufactured using microcrystalline cellulose (MCC), hydroxypropyl cellulose (HPC) and distilled water. The dry excipients were blended for 20 minutes using a Kenwood ® FP693 mixer. A defined amount of distilled water was added to the powder blend to form a wet mass that was immediately transferred to a Caleva ® Extruder 20 (screen aperture diameter size = 1 mm) operated at 35 rpm. The extrudate was collected and spheronized for 2 minutes at 800 rpm in a Caleva ® Spheronizer MBS fitted with a model 250 bowl. A numerical optimization approach was used to predict a formulation composition that would produce minimal initial CPT release, a short FLT and maximum release after 12 hours of dissolution testing. The final product was tray dried at 35°C until a constant mass was achieved. The dried pellets were screened through 2000, 1250, 800 and 315 µm screens and stored at room temperature (22°C) prior to further analysis. The effects of the addition of different water soluble (e.g. hydroxypropyl methylcellulose (HPMC)) and insoluble (e.g. ethyl cellulose (EC)) excipients on pellet formation were investigated. The influence of high and low CPT loading and the feasibility of incorporating a hydrophilic swellable polymer such as HPMC into the formulation were also investigated. The flow properties, yield, CPT content and size distribution of the pellets were determined using appropriate methodologies. The surface morphology of the pellets was assessed using a Vega ® Scanning Electron Microscope (Tescan, Vega LMU, Czechoslovakia Republic). In vitro release studies were performed using USP Apparatus 2 (Model No 73-100-104, Hanson Research, Chatsworth, CA, USA) coupled to an auto sampler. Results and discussion The yields of the pellet batches ranged between 44 and 86%. Increasing the CPT load from 5% to 85% w/w resulted in decreased pellet yield and a shift in the mean size distribution of the pellets. Inclusion of 5% w/w HPMC in the formulation resulted in poor spheronization and dumbbell-shaped pellet formation due to the plasticity of HPMC (Fig 1A). Acknowledgements The authors are grateful for the financial support from the Henderson Scholarship (SYM) and the Rhodes University Research Committee (SMMK & RBW). References (1) Krogars K, Heinämäki J, Vesalahti J, Marvola M, Antikainen O, Yliruusi J. Extrusion-spheronization of pH-sensitive polymeric matrix pellets for possible colonic drug delivery. International Journal of Pharmaceutics 2000 Apr 20;199(2):187-94. (2) Gandhi R, Lal Kaul C, Panchagnula R. Extrusion and spheronization in the development of oral controlled-release dosage forms. Pharmaceutical Science & Technology Today 1999;2(4):160-70. (3) Goskonda SR, Hileman GA, Upadrashta SM. Development of Matrix Controlled Release Beads by Extrusion-Spheronization Technology Using a Statistical Screening Design. Drug development and industrial pharmacy 1994 Jan 1;20(3):279-92. (4) Rodrìguez M, Vila-Jato JL, Torres D. Design of a new multiparticulate system for potential site specific and controlled drug delivery to the colonic region. Journal of Controlled Release 1998; 55(1): 67-77. (5) Dey NS, Majumdar S, Rao MEB. Multiparticulate drug delivery systems for controlled release. Tropical journal of pharmaceutical research 2008;7(3):1067-75. (6) Dey NS, Majumdar S, Rao MEB. Multiparticulate drug delivery systems for controlled release. Tropical journal of pharmaceutical research 2008;7(3):1067-75. (7) Sousa JJ, Sousa A, Podczeck F, Newton JM. Factors influencing the physical characteristics of pellets obtained by extrusion-spheronization. International Journal of Pharmaceutics 2002 Jan 31;232(1-2):91-106. Conclusion The type and quantity of the polymers used for extrusion- spheronization influence the formation and quality of pellets. Careful selection of excipients for the extrusion-spheronization process is essential for the formulation and manufacture of pellets with acceptable characteristics for MDDS. The high water solubility of CPT and the large surface area of the pellets contribute to rapid release from the pellets. The application of a polymeric film to the pellets may be an approach for modulating CPT release in these systems. Figure 1. SEM images of typical pellets manufactured A: 15% w/w CPT, 74% w/w MCC, 1% w/w HPC and 10 % w/w HPMC and B: 15% w/w CPT, 1% w/w HPC and 84 % w/w MCC Figure 2: Dissolution profile for CPT release from pellets manufacture using 40% w/w CPT, 59% w/w MCC and 1% w/w HPC