International Journal of Pharmaceutics 446 (2013) 136–144 Contents lists available at SciVerse ScienceDirect International Journal of Pharmaceutics jo ur n al homep age: www.elsevier.com/locate/ijpharm Formulation of lipid bearing pellets as a delivery system for poorly soluble drugs Shruti Chopra a , Natarajan Venkatesan b,∗ , Guru V. Betageri a a Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA b Chicago College of Pharmacy, Midwestern University, Downers Grove, IL 60515, USA a r t i c l e i n f o Article history: Received 10 October 2012 Received in revised form 10 January 2013 Accepted 11 February 2013 Available online xxx Keywords: Soy phosphatidylcholine Nisoldipine Solubility Extrusion Spheronization Pellets a b s t r a c t The aim of this study was to develop and characterize phospholipid bearing pellets for a poorly water- soluble drug, nisoldipine. Pellets were prepared using extrusion–spheronization technique containing microcrystalline cellulose, soy phosphatidylcholine (SPC), granulating fluid and lactose. Operational parameters such as extrusion speed, spheronization speed and residence time were evaluated. Opti- mal extrusion speed was found to be 50 rpm with a spheronization speed of 60 Hz and residence time of 2 min. Pellets were characterized for their size, shape, density, flow properties, friability, moisture content, surface morphology and thermal properties. Pellets were evaluated for their assay and in vitro drug release. Mathematical modeling was used to determine the release patterns of the pellets. Pellets were found to be spherical, 600–850 m size with <0.01% friability and had >70% yield. Scanning elec- tron microscopic (SEM) studies showed a smoother external surface and a porous internal matrix. SPC incorporated pellets resulted in improved dissolution of the drug. Pellets with SPC (20 and 30%) released >90% of the drug within 24 h. The dissolution profiles of the pellets were best fitted to Korsmeyer–Peppas kinetic model. In this study, we could successfully incorporate a lipid and a water-insoluble drug into a pellet formulation with improved dissolution profile. © 2013 Elsevier B.V. All rights reserved. 1. Introduction In the last decade, one of the major evolutions in the area of drug delivery is the recognition of formulating poorly water-soluble drugs in lipid based formulations. Various attributes of lipid based drug delivery systems being researched are augmenting drug solu- bility, bioavailability, retarding drug release, stimulating lymphatic absorption, better patient compliance by reducing side effects and taste masking (Fricker et al., 2010). Pellet based delivery is among the array of formulation approaches used for oral drug delivery systems. Their multiparticulate nature as a dosage form (filled into capsules) offers important pharmacological and technologi- cal advantages over conventional single-unit solid dosage forms. Pellets are known to overcome the poor and variable GIT absorp- tion of drugs and have shown the ability to reduce or eliminate the influence of food on bioavailability (Digenis et al., 1990; Sawicki, 2002; Basit et al., 2004). The pelletization process consists of the agglomeration of fine powders of active ingredient(s) and excipients into small spherical units. A satisfactory pellet formation process by this multi-step technique depends on optimized processing stages that include extrusion speed, spheronization speed, and residence time; ∗ Corresponding author. Tel.: +1 630 515 7104; fax: +1 630 515 6958. E-mail addresses: nvenka@midwestern.edu, natarajan.venkatesan@gmail.com (N. Venkatesan). formulation composition, moisture content of the extrudate, type of granulation liquid and physical properties of the materials used (Paker-Leggs and Neau, 2009; Hasznos et al., 1992; Pinto et al., 1993; Sousa et al., 1996, 2002). The physical characteristics of the pellets, which are directly affected by the process and formulation variables, highly influence the further manufacturing processes, such as film coating, capsule filling or tableting, and consequently the properties of the final dosage form and its biological perfor- mance (Zeeshan and Bukhari, 2010; Chopra et al., 2002; Rowe et al., 2005). Formulation of pellets may involve the use of vari- ous pharmaceutical excipients to modify the release of an active pharmaceutical ingredient. These components form a matrix sys- tem, which ensures appropriate release of the drug. The present study investigated the use of phospholipid in pellets. Various phospholipids, such as soy phosphatidylcholine (SPC), egg phos- phatidylcholine (EPC), or synthetic lecithin/phosphatidylcholine, as well as hydrogenated phosphatidylcholine (HPC), are commonly used in oral applications (Fricker et al., 2010). Phospholipids have a special amphiphilic character, making them most suitable to be used as excipients for poorly water-soluble drugs. Nisoldipine, a calcium channel blocker of the dihydropyridine class is used in the treatment of hypertension (Heinig, 1998). Nisoldipine is a BCS II drug having low solubility (5.77 × 10 -3 g/L of water) and high permeability (Yasir et al., 2010). In the present study we have made an attempt to incorpo- rate SPC along with nisoldipine into a pellet formulation. The role of SPC in the formulation was studied with respect to pellet 0378-5173/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijpharm.2013.02.029