AN OUTLINE OF VARIABLES IN PELLETIZATION BY EXTRUSION AND SPHERONIZATION Review Article RAKESH V. MISHRA * Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 411018, Maharashtra, India Email: mishrarakesh287@gmail.com , SHUBHAM G. PALDEWAR, TANAJI D. NANDGUDE Received: 26 Feb 2020, Revised and Accepted: 18 May 2020 ABSTRACT Pelletization is an agglomeration process which converts fine granules or powders of bulk drugs into small, free-flowing, spherical units, known as pellets. The pelletization can be achieved either through agitation, compaction (extrusion-spheronization), drug layering and globulation. Among the various pelletization techniques extrusion–spheronization process is preferred over other methods for the preparation of pellets as it allows the incorporation of the higher amount of drug, modified physical characteristics of the drug (density, sphericity, narrow size distribution, smoother surface) and multiple drugs can be easily combined in the same unit. This current review summarizes the findings or investigations by the researchers on various variables, including process parameters, equipment parameters and formulation parameters influencing the quality of pellets. The article also focuses on process optimization and additives used in pellets formulation. To prepare the current review search criterion used was the parameters affecting final pellet characterization in the extrusion spheronization process. The sources were peer-reviewed relevant scientific articles of recognized journals. Keywords used as filters were extrusion, spheronization, formulation parameters, process parameters, equipment parameters, moisture content, granulating liquid, drying rate, extrusion temperature, spheronizer load, pelletization. Literature survey has been done in a range of years (1992-2019) regarding the various variables of the extrusion spheronization process, which affects and has foremost impact on the final quality of pellets so as to make the review updated and comprehensive. Keywords: Pelletization, Extrusion, Spheronization, Pellets, Process parameter and Formulation parameter © 2020 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijap.2020v12i4.37277. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Pelletization is a size-enlargement process that converts small fine particles of bulk drugs and excipients into small, free-flowing, spherical units known as pellets. The pellet size range typically lies in the range of 500 to 1500 µm. Pellets as multiparticulate dosage forms are preferable over single unit dosage forms because of their potential bene fits like predictable gastric emptying, uniformity of dose, prevention of dust formation, no risk of dose dumping, flexible release patterns, less inter and intra-subject variability [1]. Pellets are commonly filled into hard ge latin capsules but can also be compressed to tablets. The pellet preparations can be coated with different polymers in order to obtain a sustained-release effect [2]. The thickness and composition of the polymer affects the release pattern. The most straight forward strategy for formulating pellets is by the extrusion spheronization method. This method was first introduced by Reynolds (1970) and by Conine and Hadley (1970), which includes four stages [3]: • Formation of the wet mass (granulation) • Forming the wet mass into extrudates (extrusion) • Separating the extrudate and adjusting of the particles into spherical form with the help of friction plate (spheronisation) • Drying of the pellets Growth mechanism of pellet The pellet growth mechanism consists of four steps as mentioned below: • Nucleation • Coalescence • Layering • Abrasion transfer and size reduction In nucleation, step particles are drawn together to form three-phase (air-water–solid) nuclei as shown in fig 1. The collision of well- formed nuclei to form larger size particles is called as coalescence. The continuous addition of material on already formed nuclei is termed as layering. Transfer of material from one particle to another without any linking in either direction is abrasion transfer. During pelletization, the three factors responsible for size reduction is either due to attrition, breakage and shatter [4]. Fig. 1: Growth mechanism of pellet (A) Nucleation, (B) Coalescence, (C) Layering and (D) Abrasion transfer [1] To prepare the current review search criterion used was the parameters affecting final pellet characterization in extrusion spheronization process. The sources were peer-reviewed relevant scientific articles of recognized journals. Keywords used as filter were extrusion, spheronization, formulation parameters, process parameters, equipment parameters, moisture content, granulating liquid, drying rate, extrusion temperature, spheronizer load, pelletization. Literature survey has been done in a range of years (1992-2019) regarding the various variables of the extrusion spheronization process, which affects and has a foremost impact on the final quality of pellets so as to make the review updated and comprehensive. Additives used in pellet formulation A wide range of materials has been investigated as additives to improve ease of processing, physical properties of the final pellets or for modifying the drug release profile (sustained release or immediate release) as indicated in table 1. International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 12, Issue 4, 2020