34 DRUG DISCOVERY AND DEVELOPMENT
Saving time and money with small-scale formulation development
Dr Michael Gamlen reports on a bench-top instrumented single- punch tablet press, a tablet testing and evaluation instrument.
U
nder the Quality by Design (QbD) paradigm new pharmaceutical
products must be correctly designed to take into account the disease and its impact on the patient; the patient population; the drug properties; the preferred route of administration (from a clinical and a marketing perspective); and the requirements of the organisation manufacturing the product.
Te preferred dosage form will frequently be an oral solid dosage form (OSD), usually a tablet that is relatively cheap to manufacture and administer, and can be produced with a wide range of release profiles. Te principal manufacturing methods for tablets are direct compression, dry granulation and wet granulation.
Each process has its own Critical Process Parameters (CPPs), and is affected by the Critical Quality
Fig. 1. The Formulation Cycle.
Attributes (CQAs) of the drug substance. Te Product Control Strategy (PCS) is based on understanding the links between the formula and process, and the CPPs and CQAs, so generating the data to support the PCS is key to meeting the regulatory expectations of Quality by Design. Te development of the formulation and process is usually an iterative one in which the formulation or process is adjusted based on evaluation of intermediates and products (Fig. 1).
All products and intermediates must be carefully evaluated to understand the impact of changes to the formulation and process on product quality, and to support the QbD process.
Te manufacturing scale used during formulation development depends on the amount of drug substance, and the equipment, available.
Te Gamlen Tablet Press (Fig. 2) is a versatile and relatively low- cost tablet-testing instrument that can be used, for example, for designing tablet formulations on a small scale under the Quality by Design (QbD) paradigm. It can help in the evaluation of small amounts of material, in particular for direct compression processes and dry granulation. Te latter is becoming increasingly popular: the first compression step can be done on either a tablet (or slugging) press or a roller compactor. With the Gamlen Tablet Press batches have been made from as little as 5g of material, compressing a 15mm slug of 1 to 2mm thickness. Te properties of the slugs have been found to correlate well with ribbon from the smallest scale of operation for a roller compactor that was 100g upwards.
Compression Small scale compression under controlled conditions requires instrumentation using an instrumented tablet press, a compaction simulator or the Gamlen Tablet Press. Tis enables measurement of compaction, ejection and detachment force – all for the same event and in real time, using simple software.
Te simplest way to compare formulations is by assessing their ‘tabletability’ – the relationship between compaction pressure and the tensile fracture stress of the tableted product. Tis provides a sensitive measure of both formulation and process effects.
Te superiority of wet
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