Authors
Chandramouli R
JMP
Muralidhara A
JMP
Objective
Use Mixture/formulation design to optimize multiple responses related to bioavailability of a drug.
Background
Bioavailability is an important factor in determining the efficacy of a drug. It is defined as the amount of the drug that reaches the bloodstream and thereby elicits action. There are many approaches to enhancing bioavailability, and one such is SMEDDS (self micro-emulsifying drug delivery system). SMEDDS are lipid-based drug delivery systems designed to improve medication dissolution in the gastrointestinal tract.
A pharmaceutical company (name kept confidential) is working on a pharmaceutical formulation to improve the bioavailability of a hard-to-dissolve active pharmaceutical ingredient (API). The company follows a Quality by Design (QbD) framework for development. An understanding of the critical quality attributes (CQAs) is a regulatory requirement and defines the quality target product profile (QTPP).
The API used in this formulation belongs to the biopharmaceutical classification system class of low solubility and permeability, which in turn constrains bioavailability. This formulation is a three-component system, comprising oil, surfactant, and cosurfactant. As part of the process, the API is solubilized in the oil and is emulsified using a surfactant and cosurfactant system to enhance the bioavailability of the drug. Thus, the drug-loaded micro-oil emulsified droplets have a better bioavailability profile than normally administered drugs. Bioavailability is a surrogate measure and can be influenced by oil droplet size, emulsification time, the amount of drug loaded in the oil, and the amount of drug released.
The Task
The development team has been tasked with creating a formulation that improves bioavailability. From domain expertise, it is understood that the lower the droplet size and emulsification time, the higher the bioavailability. At the same time, the amount of drug loaded in the oil and the amount of drug released upon administration have a direct influence on bioavailability. The team has the following tasks:
- -To create an experimental design to conduct the trials. The team has a limited budget and can afford only 10 trial formulations.
- -To identify the optimal mix of ingredients (oil, surfactant, and cosurfactant) to maximize the bioavailability.
With this background, the team decided to leverage DOE, a scientific way to actively learn, perform smarter experiments, and find the optimal factor settings.
The descriptions of the responses and factors, along with the limits, are presented on the PDF linked below.