Research paper The role of formulation excipients in the development of lyophilised fast-disintegrating tablets Rahul Chandrasekhar, Zahra Hassan, Farhan AlHusban, Alan M. Smith, Afzal R. Mohammed * Medicines Research Unit, Aston University, Birmingham, UK article info Article history: Received 30 September 2008 Accepted in revised form 21 November 2008 Available online 3 December 2008 Keywords: Fast-disintegrating tablets Gelatin Saccharides Lyophilisation Pluronic F127 Carbopol 974P abstract Despite recent success, many fast-disintegrating tablets (FDTs) still face problems of low mechanical strength, poor mouth-feel and higher disintegration times. This study aimed to optimise FDTs using a progressive three-stage approach. A series of hardness, fracturability and disintegration time tests were performed on the formulations at each stage. During Stage I, tablets were prepared in concentrations between 2% and 5% w/w, and were formulated at each concentration as single and combination bloom strength gelatin (BSG) using 75 and 225 BSGs. Analysis revealed that both hardness and disintegration time increased with an increase in gelatin concentration. A combination (5% gelatin) FDT comprising a 50:50 ratio of 75:225 BSGs (hardness: 13.7 ± 0.9 N and disintegration time: 24.1 ± 0.6 s) was judged the most ideal, and was carried forward to Stage II: the addition of the saccharides sorbitol, mannitol and sucrose in concentrations between 10% and 80% w/w. The best properties were exhibited by manni- tol-containing formulations (50%-hardness: 30.9 ± 2.8 N and disintegration time: 13.3 ± 2.1 s), which were carried forward to the next stage: the addition of viscosity-modifying polymers to improve mouth-feel and aid pre-gastric retention. Addition of carbopol 974P-NF resulted in the enhancement of viscosity with a compromise of the hardness of the tablet, whereas Pluronic F127 (6%) showed an increase in disintegration time and viscosity with retention of mechanical properties. Ó 2008 Elsevier B.V. All rights reserved. 1. Introduction Oral fast-disintegrating dosage forms, also known as ‘fast-melt’, ‘ fast-disintegrating’ or ‘ fast-dissolving’ dosage forms, are a relatively novel dosage technology that involves the rapid disintegration or dissolution of the dosage form, be it a tablet (the most common form) or a capsule [1–3], into a solution or suspension in the mouth without the need for water [4,5]. The dosage form begins to disin- tegrate immediately after coming into contact with saliva, with complete disintegration normally occurring within 30–50 s after administration [6]. The solution containing the active ingredients is swallowed, and the active ingredients are then absorbed through the gastrointestinal epithelium to reach the target and produce the desired effect. Oral fast-disintegrating tablets (FDTs) are designed for the pur- pose of improving patient acceptance and compliance. A survey of 6158 GP patients conducted in Norway indicated that approxi- mately 26% of all patients do not take their prescribed medication as they encountered problems when swallowing conventional tab- lets. Often, the main complaints are the size, surface and taste of the tablets [7,8]. Oral FDTs help overcome some of these problems: the rapid disintegration of the tablet into a solution (containing the drug) enables those who find difficulty in or experience discomfort when swallowing, to have a more ‘patient friendly’ experience. Target groups for oral FDTs are wide-ranging as people of all ages can experience difficulty in swallowing conventional tablets and capsules. This includes children and the elderly who either experience difficulty and cannot swallow or have not learnt to swallow the conventional solid dosage forms. In addition, institu- tionalised psychiatric patients as well as hospitalised or bedridden patients suffering from a variety of disorders such as stroke, thy- roid disorders, Parkinson’s disease and other neurological disorders such as multiple sclerosis and cerebral palsy [4] also find difficulty in swallowing and require ‘fast-melt’ tablets because of their phys- ical condition. The convenience and ease of using FDTs is also important to normal consumers, with some adults preferring these dosage forms as they are easy to handle and swallow, can be taken without water and have a rapid onset of action [1,9]. For example, patients with a limited access to water would also find such FDTs extremely beneficial [2,4]. In addition to improving patient compliance, FDTs have been investigated for their potential in increasing the bioavailability of poorly water soluble drug through enhancing the dissolution pro- file of the drug [10,11]. Moreover, pharmaceutical companies also have commercial reasons for formulating FDTs. As a drug reaches the end of its patent, the development and formulation of the drug 0939-6411/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2008.11.011 * Corresponding author. Aston Pharmacy School, Aston University, Aston Trian- gle, Birmingham B4 7ET, UK. Tel.: +44 121 2044183. E-mail address: a.u.r.mohammed@aston.ac.uk (A.R. Mohammed). European Journal of Pharmaceutics and Biopharmaceutics 72 (2009) 119–129 Contents lists available at ScienceDirect European Journal of Pharmaceutics and Biopharmaceutics journal homepage: www.elsevier.com/locate/ejpb