Formula Optimization Key to Product Development

When developing a new product, formulators have myriad variables to consider, from determining the optimal thickness at a given run weight to adjusting excipients to provide controlled release. What are the barriers to entry? Is the delivery system appropriate for the product? What type of packaging system is needed? What testing methods are required?

Producers of dietary supplements must be efficient, cost effective, productive and, at the end of the day, able to deliver a working product. This is easier said than done, especially as the demand for extended release products grows. Formulation scientists at contract manufacturing companies must experiment and research more than ever. Such research starts at the earliest stages of development—toward understanding not only what the customer wants, but how the materials will perform.

A final product is only as good as the raw materials, and formulation optimization begins with proper sourcing. The days in which manufacturers sourced raw materials only from a limited group of trusted suppliers or simply purchased the lowest priced material are over. Legislation changes, stricter regulations and the general increase in quality awareness have changed the playing field. The demand for lower-cost production is creating markets in many countries. Consequently, the sourcing process can be an obstacle in the production of consistent, high-quality products. This need to understand the global commodity of suppliers and the actively changing market has led many companies to appoint a principal sourcing agent dedicated to raw materials.

However, procuring material from a reliable source is only the first step. Pharmaceutical applications require extensive material testing (i.e., particle size, polymorphism, solubility, water content, binary studies, etc.) to confirm the physicochemical properties and quality. While comprehensive testing is a given for prescription products, manufacturers are starting to adopt such standards for dietary supplements as well. By applying rigorous testing and stability protocols to all formulated products, such firms are paving the way for higher quality products. Tighter control on the raw materials equates to tighter control on the products and fewer, if any, customer complaints.

Once the material is selected and timeline solidified, it is time to set a product goal, which must include dosage form, size, delivery mechanism and appearance. Determining these aspects of the final product helps establish formulation strategies and keeps formulation efforts focused and efficient. Instead of using the common trial and error method of product development, an arguably better approach is to use existing research to inform and help create an experimental design in which independent variables are identified and modified. This model ensures more stability and an optimal product. The FDA Guidance outlined in International Conference on Harmonization (ICH) Q8 describes the establishment of a design space. Implementing an experimental research methodology represents an efficient approach for solving such optimization problems. Consider how formulators are regularly faced with the optimization of an excipient mixture composition. Using the design space, the focus is preparing a product with the required characteristics, determining the optimal choice in each excipient category (i.e. binders, diluents, glidants, lubricants, etc.) and the ideal level of each excipient.

One common oversight made by less experienced contract manufacturers is the failure to include the production team in the formulation process. Open communication is necessary throughout all areas of the developmental process. As progress is made on trial batches, it is critical to be mindful of both the final production-scale process for the commercialized product as well as the company’s manufacturing capabilities to support the product. Keeping the end process in mind will save time in the scale up and commercialized production and the product will see the market that much sooner.

Developing a product utilizing the design space concept will help in preparing a formulation or product development report, a summary of all work done from initial conception to the final commercialized product. This story tells the tale of how the product evolved into an optimal, commercialized entity. Setting a target for the different parameters and giving reasoning for the specifications will display a higher degree of knowledge and understanding of the product, and the critical attributes will be identified and understood.

Developing dietary supplements requires the ability to wear many hats while keeping a keen eye focused on the urgency of moving to market on time. Utilizing the appropriate technology is only half the battle. The real test is in formulating a robust, optimized product. The challenge is there, and the stage is set; success depends on the execution.

Jeffrey Reingold, Ph.D., is the manager of research and development (R&D) at Contract Pharmacal Corp. (ContractPharmacal.com), a Hauppauge, N.Y.-based full-service contract manufacturer and packager of dietary supplements, OTC drugs and pharmaceuticals.