Excipient economics

Excipio Economics can significantly improve the efficiency of oral dose form development. Glynn Wilson, Matthew Heil, & Robert Hemley explain how it works

In recent years, mounting pressure in the pharmaceutical industry to lower the cost of drugs has required pharmaceutical companies to examine more aggressively their drug development processes to improve time and cost efficiencies.

The need for early commitments to final formulations and processes, and approaches that predict large-scale performance is more acute than ever. One important yet often overlooked area in this pursuit is excipients, which can make a significant difference in improving the efficiencies of oral dosage form development.

An effective new approach to improving cost and time efficiencies in the development and manufacturing of tablets is the use of a new generation of high functionality excipients such as ProSolv SMCC, or novel combinations of existing excipients that have new properties and multiple functions. These excipients offer a valuable strategy to meet the challenges facing r&d, manufacturing and regulatory professionals today as they strive to make drugs optimally active and reduce the time to market.

JRS Pharma has termed this new strategy 'Excipio Economics'. It provides an effective way to measure the cost and time impacts of these excipients across the formulation and manufacturing processes, and offers a set of tools for integrating economic and technical criteria into excipient and process selection.

tablet development

Excipio Economics uses a computer model to examine alternative scenarios and measure the relative economic effect of different formulation components and manufacturing processes.

The process requires integrating strategies for formulation development, clinical manufacturing and commercial manufacturing at the start of the development process so that the options for tablet development can be considered from both technical and economic perspectives.

There is growing recognition of the role of new excipients in improving product performance and meeting new challenges in development and manufacturing. An example of a major innovation in high functionality excipients that addresses many of today's formulation and manufacturing challenges is a patented formulation of microcrystalline cellulose (MCC) and colloidal silicon dioxide from JRS Pharma.

This excipient provides increased compactibility, enhanced flow, and improved uniformity, enabling a direct compression manufacturing process with all the benefits of wet granulation.

granulation products

The product also provides manufacturing efficiencies, such as reduced excipient use, product loss and production cycle time; increased production output; and elimination of scale-up issues.

A case study of the formulation of levothyroxine demonstrates how direct compression processing with ProSolv SMCC preblending can lead to improved drug content uniformity and a better product for a difficult-to-formulate active.

Preparations with levothyroxine are known to exhibit deficiencies in content uniformity, stability and shelf-life.

In the original product, content uniformity using MCC/lactose wet granulation was 5-8%, but with ProSolv SMCC, uniformity was 0.9-1.0%. This formulation demonstrated excellent stability and shelf-life in contrast to the original wet granulation product, which lost 18% of the drug potency after three months of accelerated stability.

Conversion to a direct compression process significantly reduced production costs of this high volume product.

In the case of a new chemical entity with difficult formulation characteristics, the substitution of an SMCC formulation solved multiple formulation issues. After 15 formulations were tested without success, a direct compression formulation using ProSolv SMCC reduced friability problems and met all other target specifications using only two excipients.

The benefits were an 80% reduction in time for formulation selection, minimisation of active consumed during development, flow properties suitable for high speed tableting, reduced total tablet cost of 17%, avoidance of more costly wet granulation and roller compaction processes, and reduction in disintegration time.

The ease of scale-up through clinical trials and for commercial manufacturing led to an earlier entry to market.

The value of earlier entry on a product earning $20m in its first year would be more than $1.8m. This demonstrates how decisions made in one phase of formulation can have bottom line effects on areas that traditionally have not been included in the planning of oral dosage forms.

Excipio Economics emphasises the interrelatedness of r&d, manufacturing and marketing to optimise the creation of oral dosage form products.

JRS believes that Excipio Economics can effectively bridge the gap between r&d and manufacturing, and integrate formulation and economic considerations with those of commercial manufacturing decisions, and provides a valuable means to assess the economic impact of new excipients in the development and manufacturing of Rx, generics and nutraceuticals.