Garnet E. Peck Symposium - 2005 Speaker Biographies

• The Use of Artificial Intelligence 'Expert Systems' as Formulation and Process Tools to Overcome the PAT Challenges - Metin Çelik
• The Role of the Pharmaceutical Scientist in Developing Niche Products - Allen Chao
• Design and Formulation Criteria for Tablets to be Film Coated - Charles Cunningham
• The Development and Use of Deterministic Models for Formulations Development, Using Pipeling and Algorithmic Methods - Michael J. Doyle
• Robust Tablet Design Pre-Validation Approaches for Developing Low-Dose Direct Compression (DC) Products with Increased Probability of Meeting PAT Criteria - Alice C. Martino
• Near Infrared Monitoring of Roller Compaction - Garnet E. Peck
• Modeling a Horizontal Pan Tablet Coating Process - Carl Wassgren

The Food and Drug Administration took a proactive approach to bring the scientific and risk-based framework founded on pharmaceutical process understanding which is essential for prediction of product quality attributes. As a result of this proactive approach, the PAT initiative gained momentum amongst the pharmaceutical scientists. The PAT applications require the understanding of chemical, physical, microbiological, mathematical, and risk analysis conducted in an integrated manner, many scientists are confused what is PAT and what is not, and how to implement PAT applications.

In this presentation, some of the challenges related to the excipient selections, formulation and process development for PAT applications will be addressed and the use of expert systems to overcome these challenges will be discussed by presenting the case studies.

Aqueous film coating is a process that is routinely employed as a unit process in the preparation of pharmaceutical solid dosage forms. During the last 30 years, there has been significant research into coating formulations and coating processes. In focusing on these areas, we have paid less attention to issues that relate to the preparation a suitable tablet or substrate to which a coating will be applied. This presentation will highlight important tablet core characteristics that should be considered early in the development of a dosage form that will be film coated.

The benefits of film coating, which include providing a unique dosage identity, enhancing appearance, masking bitter tastes and improving tablet stability more than justify the exposure of tablets to the rigors of the film-coating process. One must, however, be cognizant that a dosage form which will be film coated should be robust enough to withstand the additional stress imparted by the film-coating process. Tablets must be formulated and designed using more stringent criteria than for uncoated dosage forms. In a typical film-coating process, the tablets (and the applied coating) are constantly subjected to mechanical duress along with conditions of elevated temperature and humidity.

The first section of this presentation will focus on the effect of tablet design on the quality of the film-coated tablet. Guidelines will be presented for selecting tablet shapes, physical specifications and logo designs that will eliminate many of the problems encountered in film-coating processes.

Of equal importance is the formulation of the tablet itself. Active ingredients and the choice of excipients used in the formulation can have a profound effect not only on the mechanical strength of the tablet but also on film adhesion and stability. The advantageous and detrimental effects of commonly used tablet excipients on film-coating quality will be discussed.

Many of the ingredients chosen in initial tablet formulation development can have a significant impact on aqueous film-coating quality. Decisions that have a great impact on coating quality and ultimate tablet appearance are often left until later stages of development . We can better ensure success in the film coating process if we reconcile the formulation and design stages early in the development process.

The use of QSAR (quantative structural activity relationship) analysis has been of invaluable help in modern synthetic and high throughput pharmaceutical discovery. However, this use of structural screening models has largely ignored or sublimated the needs of delivery, development and production steps in the overall production process. This talk discusses approaches to these key variables in the overall effectiveness of an active pharmaceutical ingredient formulation. It also discusses the impact the development of predictable models can have on the quality control and predictability of pharmaceutical manufacturing.

• Low potency DC tablet formulation design
  • API crystal properties
  • morphology, crystallinity and aggregation state
  • modelling approaches to content uniformity prediction
  • avoidance of "hot spots"
• Prevalidation focus on understanding what you don't know and rational process selection
• Several Case Studies reviewing the selection of API properties and/or dosage form processes

Near infrared (NIR) spectroscopy can be used for real-time monitoring and/or control of constant uniformity (CU), tensile strength (TS) and moisture content (MC) of the ribbon during roller compaction. Moisture acts as a plasticizer, facilitating compaction by changing particle arrangement and/or deformation behavior. The force required to achieve desired level of densification can be predictably reduced by increasing the moisture level of the powder blend. NIR was used for monitoring and for developing models to predict in real-time during roller compaction such parameters as tensile strength, moisture content, content uniformity and post-milling particle size distribution. The experiments used in this study included the effect of changing roll speed, vertical and horizontal feed speeds and ratios of the various speeds. Models developed on NIR spectra collected off-line were successfully used to monitor and predict real-time output during roller compaction.

This talk will present the use of soft-particle, discrete element method (DEM) computer simulations for investigating a horizontal pan, tablet coating process. The computer model simulates the dynamics of each tablet contained within the pan. Using the model, predictions can be made for each tablet's position, orientation, and speed as well as the contact forces acting on the tablet. Coupling the DEM results with a separate spray coating model, predictions of the inter- and intra-tablet coating variation may also be made.