Using Simulation to Improve Drug-Delivery Effectiveness

Pharmaceutical companies are responding to the high cost of introducing new drugs to market in different ways.
Nov 01, 2011

Pharmaceutical companies are responding to the high cost of introducing new drugs to market in different ways. For new drugs, companies are examining drug products and their delivery systems far earlier in the design phase than they have in the past to ensure success of the new drug and device combination. At the same time, existing APIs are being repurposed for new therapeutic treatments or delivered using improved formulation and delivery methods that may better resolve the physiological, biochemical, and physicochemical barriers. These shifts have increased the industry's focus on the drug-delivery platform as an enabling technology that can optimize drug efficacy and cost-effectiveness.

Simulation software is one technology that can improve device performance by allowing pharmaceutical companies to virtually model and prototype the delivery of new drugs. Various properties can be examined, including the drug's composition, particle size, flow, andhuman physiology.

Numerical simulation tools, such as finite element analysis (FEA) and computational fluid dynamics (CFD) provide a way to rapidly and economically examine a wide array of drug-delivery technologies. Early in the design cycle, numerical simulation identifies designs and operational conditions that might not meet therapeutic requirements, thereby allowing companies to address these and to develop accurate, safe, and effective design before the first prototype is developed. Later on, models can be constructed to simulate the actual drug-delivery process to humans. Although these advanced studies entail more upfront effort, especially if validation is required, they provide significant advantages over experimentally driven develoment processes. Therefore, they can decrease the chance of design changes after the product enters animal or clinical trials. This article describes these simulation technologies and related case studies.

Computation fluid dynamics tools

Because of the fluidic nature of drug delivery, CFD tools are commonly used to understand and optimize the delivery process. CFD takes advantage of numerical methods to solve the fundamental equations for fluid flow and heat/mass transfer. The process begins by creating the medical device in a computer aided design (CAD) tool or in other solid modeling software. The next step is to decompose the domain into a computation grid or mesh. Anatomic structures are incorporated as needed using one of two approaches:

  • Creating an idealized anatomic model (using solid modeling software); or
  • Extracting the anatomic structure from medical-scan images using segmentation software, such as Mimics (Materialise) or ScanIP (Simpleware).

Segmentation tools combine the anatomic data with the device, create a mesh, and export the meshed assembly in a format readable by most leading commercial simulation software. The user enters material property data, initial and boundary conditions, and submits the job to the CFD solver. Once the problem is converged, the user visually and quantitatively reports results for fluid flow, density, drug concentration, and other variables. Cut planes and surface plots are the most common way of displaying the results. Alternatively, one can extract point, surface, or volumetric results for quantitative comparisons to experimental or other data.