Starch - the natural excipient choice

Dr Fred Heinze, business manager, Healthcare Europe, National Starch, highlights the role of the next generation of natural polymer functional excipients

Excipients are increasingly recognised for the critical role they play in pharmaceutical products. They have special functionalities in formulations and contribute enormously to the efficacy of a product. They bind tablets together under the stress of direct compression; control the release of active ingredients; help tablets disintegrate and dissolve efficiently and influence absorption.Formulators of finished dosage forms are dependent on excipient manufacturers to provide substances which are uniform in chemical and physical characteristics, offer processing benefits and meet the highest quality to - preferably - single global standards. New multi-functional excipients, which comply with all regional pharmacopoeia requirements simultaneously and can therefore be used worldwide, have been developed.

administration routes

The most commonly used route of administration is via solid dosage forms such as tablets, capsules and powders. This is the preferred method - over 90% of drugs are applicable to solid dosage, which offers several benefits: accurate dosing, inexpensive transportation and increased stability in comparison with liquid forms.

There are two main tableting techniques: wet granulation and direct compression. In wet granulation, the active ingredients and excipients are mixed together and then agglomerated with a wetting solution. This mixture is then dried and granulated. In direct compression, the dry ingredients are blended to a homogeneous mixture and put directly into the tablet press.

Starch, a natural polymer, is one of the most common excipients used in pharmaceutical solid dosage forms. It offers formulators the option of using a natural, renewable and abundant excipient ingredient to fulfil their needs. Its versatility allows experimentation with its properties and precise customisation. Latest advances in speciality pregelatinised starch technology bring new opportunities to tablet binding for both wet and dry dosage forms.

Pregelatinised starches are excipients that have been processed chemically and/or mechanically to rupture all or part of the granules in the presence of water and subsequently dried.

Of most interest and relevance to the pharmaceutical developer is the fact that compendial pregelatinised starch can be provided as a fully pregelatinised starch excipient or as a partially pregelatinised starch excipient.

Pregelatinised starches bring a number of benefits in both processing and performance: they enhance flow and compressibility and can be used as binders in direct compression as well as wet granulation. National Starch's multi-functional high purity pregelatinised starch excipients - the Uni-Pure range - have a number of advantages in use. They allow simplified processing as they swell in cold water and therefore reduce time/costs compared with traditional starch paste preparation.

wet granulation

In general, excipients are used as purchased, within the limits of the relevant pharmacopoeial monograph. Batch variations of excipients cannot be tolerated as functionality of the finished drug application might be affected. For drug quality and safety reasons, the highest achievable batch-to-batch consistency generally is required. The quality achieved from expert manufacture of pregelatinised starches makes significant differences for formulators in terms of purity and consistency.

Wet granulation is the chosen method for poorly compressible drugs such as acetaminophen. Most pharmaceutical actives are difficult to compress directly and therefore need to be granulated. Granulation can yield the following benefits: improved free-flowing properties, density of the bulk powder and homogenicity of the powder, better compressibility, enhanced drug release, reduced dust during process and finally, improved solid drug appearance.

The process starts with the wet massing of powders, wet sizing or milling, then proceeding to the drying step followed by dry sieving and compression.

National Starch recently conducted trials to compare its fully pregelatinised maize starch, Uni-Pure WG, with other commercially available binders. The objective of the tests was to investigate the functionality and tablet properties of different binders. The binders used in the study are shown in table 1. Table 2 shows the formulation, table 3 the method of preparation, and table 4 highlights the analysis undertaken.

Granulation was performed in a low shear Hobart mixer, where the pre-blended active ingredient, lactose and each binder were mixed for one minute prior to the addition of water. This was added in small quantities at a time and the powder was mixed until granulation was completed. The powder blends, with the added silica and Mg-stearate were compressed on an instrumented Picola 10-station rotary tablet press. Compression forces during tablet manufacture were recorded using the Director data acquisition system (SMI, NJ).

The trials showed that the compression profiles for products one, three and four were similar (figure 1), while tablets made from product two were slightly harder. Table 5 shows the disintegration times for tablets. The tablet formulation including the starch binder exhibited significantly shorter disintegration times compared with the tablets containing Povidone or HPMC. Binder selection has been identified as a significant variable affecting tablet disintegration. According to this study, Uni-Pure WG gives formulators the opportunity to manufacture tablets with strong binding properties and significantly faster disintegration than the synthetical excipients investigated.

This clearly adds value to the dissolution profile of active drugs granulated with the pregelatinised starch, figure 2.

Tablet formulations containing the starch binder released 100% of the drug within 30 minutes, thus fulfilling USP requirements. The tablets containing the Povidone and HPMC binders exhibited, in this model, sub-optimal drug release and dissolution characteristics.

strong benefits

Use of the starch product can, therefore, lead to highly efficient processing, resulting in strong benefits for final tablet properties; these include high mechanical resistance as well as excellent disintegration (figure 3) and dissolution.

Thus it also offers economical advantages over conventional synthetic polymer tablet binders. The optimum performance of excipients depends on various factors, including the physico-chemical properties of the drug, type of filler and the process used to make the granule, tablet or capsule.

Latest advances in natural polymer science meet specifications both in terms of functionality - they provide binding, act as filler/diluents and disintegrants - and regulatory requirements, including NF/USP, Ph Eur and JPE, while offering consistently high purity excipients.