“Monitoring Punch Forces and Punch Movements as an AID to Developing Robust Tablet Formulations”

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Abstract
The benefits of commencing the pharmaceutical development program for a new drug entity as soon as practical are obvious. However, the ability to do so is controlled by many factors including limited availability of drug substance and very little information on pharmaceutically relevant properties. It is this data which the formulator must begin to collect as soon as any material becomes available. Establishing the physico-chemical characteristics (often referred to as ‘preformulation’) covers a wide range of attributes. This paper only considers those which can be investigated by use of instrumented compaction equipment The first experiments should include establishing the intrinsic compactibility of the compound by preparation of simple compacts of drug substance under controlled conditions and with essentially no additives except die wall lubrication. Irrespective of whether compacts are formed or not, the raw data collected from the instrumentation may be used to give an initial reading of this important property of the material On completion of these tests on drug substance, the development process then follows a pattern of making simple tablets and testing them for dissolution, strength, content uniformity, etc. Instrumentation can improve the efficiency of this process in several ways by providing information on predominant compaction mechanisms, a predictive capability of strength and maybe even dissolution. It will also create a data base of ‘normal’ results and a rapid, easy screen for variability If the work is being carried out on a sophisticated test instrument or simulator, the formulations may be subjected to high speed tabletting cycles in order to obtain a measure of the strain rate sensitivity. Several reports have now shown the effect of strain rate on properties such as tensile strength of tablets and their disintegration time As more drug substance becomes available a set of experiments designed to identify a commercializable formulation is carried out. This is also an appropriate point to transfer the processing to a rotary tablet press (if not already done), but the conditions must be controllable and precisely known. From these experiments a primary and at least one back-up formulation are identified, including processing conditions as well as composition The first clinical material, using the preferred formula and manufacturing instructions, can now be made. During the ensuing development phases the emphasis on utilisation of the instrumentation changes, but many of the measurements already referred to, are still useful. Much of the data resulting from the overall program described, can provide an impressive addition to the “Formulation Development” section of any submission!