Functionality evaluation of co-processed excipients

Tablets constitute about 80–90% of dosage forms commonly prescribed by medical practitioners for therapeutic management of disease conditions. It is a solid dosage form that exercises advantages over other dosage forms because of its ease of administration, stability profile and amenable to large-scale production. Tablet making involves the addition of a category of substances known traditionally as excipients. Though commonly referred to as the inactive components of a tablet formulation, they are functional in nature because they contribute significantly to the processing, stability, manufacturability and performance of tablets as a dosage form. Depending on the functionality, excipients may be classified as diluents, disintegrants, binders, lubricants, glidants, etc. They are usually added in stated amounts to facilitate the development of a robust tablet product.

Most tablet formulations are prepared by wet granulation and require the addition of all the listed excipients. One critical excipient that is incorporated in tablet formulations by wet granulation is the diluent. Diluents also known as fillers or bulking agents are routinely added in formulation development to increase the bulk of the formulation and to bind other excipients with the active pharmaceutical ingredient (API). The use of diluents becomes more significant in tablet formulations of low-dose API where the diluent occupies a larger proportion of the formulation. Hence, the properties of diluents become extremely important and can significantly influence the final product property. Studies have been carried out to characterise the mechanical properties of widely used pharmaceutical diluent powders to understand how their mechanical properties impact on the manufacturing performance and properties of the final product (Zhang et al., 2017). These diluent powders are more or less single component excipients (SCEs) like lactose, starch, mannitol, microcrystalline cellulose (MCC), which have been used in tablet formulation by wet granulation. However, due to the limited functionality of SCEs in tablet formulation, attention has shifted to the development of novel excipients with improved functionality.

Co-processing as a particle engineering technique has been used to develop novel excipients with improved functionality. This technique involves the combination of two or more excipients in optimal proportions at the sub-particle level using a defined method that promotes synergy of properties in composite particles while minimising the limitations of the constituent excipient in the final product. Some of the functionality improvement recorded with co-processed excipients (C-PEs) includes enhanced flowability, compressibility, dilution potential and low lubricant sensitivity and/or moisture sensitivity (Nachaegari and Bansal, 2004). Many of these C-PEs have been designed originally as filler-binders in direct compression formulation (Wang et al., 2015), as superdisintegrating agents for orodispersible tablets (Daraghmeh et al., 2015) and as drug-release retardants in controlled release formulations (Choudhari et al., 2018). No study has reported the use of C-PEs as diluents in wet granulated tablet formulations.

Considering the improved tableting profile of C-PEs, changing the diluent type in a wet granulated tablet formulation from an SCE to a C-PE is likely to result in better tableting properties of the drug product. Hence, the aim of this study is to evaluate the tableting properties of C-PEs as diluents in a wet granulated formulation of metronidazole tablets. Two samples each of lactose-based C-PEs (Ludipress®, StarLac®) and MCC-based C-PEs (Prosolv®, AVICEL®HFE) were evaluated as diluents in comparison to their SCEs (lactose, MCC).

Download the full article here: Functionality evaluation of co-processed excipients as diluents in tablets manufactured by wet granulation

or continue reading here: Eshovo Apeji, Y., Muhammad, IY., Kehinde Olowosulu, A., Owoicho Okpanachi, G., & Rukayat Oyi, A. (2021). Functionality evaluation of co-processed excipients as diluents in tablets manufactured by wet granulation, European Pharmaceutical Journal (published online ahead of print 2021), 000010247820200010. doi: https://doi.org/10.2478/afpuc-2020-0010

Materials

Metronidazole (CDH laboratory Chemicals, India), lactose (DFE Pharma, Germany), maize starch (Burgoyne Burbidge & Co. India, Mumbai), Acacia (Kerry Ingredients and flavours Ltd, Ireland), StarLac® (Roquette Pharma, France), Ludipress^® (BASF SE, Germany), MCC, Prosolv^®, sodium stearyl fumarate (JRS Pharma, Germany), AVICEL®HFE (FMC BioPolymer AS, Norway), colloidal silicon dioxide (Evonik Industries, Germany), distilled water.