Preparation and scale up of extended-release tablets of bromopride

Guilherme Neves Ferreira,Aline Guerra Manssour Fraga,Carlos Rangel Rodrigues,Luiz Cláudio Rodrigues Pereira da Silva,Lucio Mendes Cabral,Valéria Pereira de Sousa,Luiz Marcelo Lira,Marcos Giovani Rodrigues Silva,Helena Carla Castro

doi:10.1590/s1984-82502014000200008

Abstract

Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE) can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm) software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm) software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.

Highlights

The international quality standards of pharmaceuticals, as recommended by pharmacopeias and regulatory agencies, state the importance of robust manufacturing processes, in order to ensure both minimal variation between batches and adequate formulation development
All matrix concentration that do not led to a controlled release profile were excluded from the study, by listing in Table I only those that showed a sustained release profile of BPD
hydroxypropyl methylcellulose (HPMC) and ethyl cellulose matrices are usually used in sustainedrelease tablet preparation (Velasco et al, 1999; AbdelRahman, Mahrous, El-Badry, 2009)

Summary

Introduction

The international quality standards of pharmaceuticals, as recommended by pharmacopeias and regulatory agencies, state the importance of robust manufacturing processes, in order to ensure both minimal variation between batches and adequate formulation development. Among the different techniques used for manufacturing tablets, direct compression is the most practical and cost-effective (Jivraj, Martini, Thomson, 2000; McCormick, 2005). For this process, tablets are obtained from the mixture of active ingredient and diluents, followed by the addition of lubricants, disintegrants and, by compression of the final mixture. Tablets are obtained from the mixture of active ingredient and diluents, followed by the addition of lubricants, disintegrants and, by compression of the final mixture This method may be employed for immediate and extended-release forms (Skelly et al, 1993). The development of new sustained-release BPD tablets represents an industrial solution for cost reduction, leading to a more reproducible batch to batch drug release profile

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