API physicochemical characterization is vital in dry powder inhalation (DPI) formulation development. Complete understanding of the physical and chemical properties of the API could support in optimizing the formulation to achieve desired product performance and Ultimately, it safeguards the entrance of safe and effective DPI products on the market for treating respiratory conditions.
INTO can help you in understanding and optimizing the appropriate active ingredient for your respiratory product. Support can be gained throughout the full process or by focusing on multiple parts or individual part of the process.
Development (R&D) phase
Aim: Find the right solution through DOE approach studies
What we do: Screen and select the most suitable crystallization path
- Polymorphism
- Particle size (preliminary)
- Morphology
Particle engineering
Aim: Facilitate formulation development and reduce issues downstream
What we do: Target specific morphology/PSDs
- Pilot/Commercial Micronization & Sono-crystallisation
Pre-engineering
Aim: Guarantee API reliability though MVA analysis
What we do: Control API characteristics
- Powder flowability
- Specific Surface Area
- Surface free energy
Post engineering
Aim: Have a full understanding of engineered API properties
What we do:
- Morphology
- Particle size
- Amorphous content
- Water content
- Specific Surface Area
- Rugosity
- Surface free energy
Commercial production
Aim: Support with extensive testing characterization
What we do: Asses consistency and reproducibility
- Morphology
- Particle size
- Water content
- Hygroscopicity
Developing Dry powder inhaled formulation is a complex process. Therefore, challenges can easily arise in each step of the development; whether being attributed to achieving desired aerodynamic performance or challenges encountered during scale-up process. INTO can support you by understanding the critical quality attributes, identifying the key variables impacting the formulation, and employing risk-based strategies. This to obtain a robust and reliable DPI formulation.
Whether you seek support regarding a specific challenge or throughout the development process, INTO is able to tailor the support you need. Below you will find an outline of what INTO can offer.
QbD based formulation development
Aim: Develop QbD and risk assesment protocol
What we do:
- Risk assessment critical attributes
- Define control strategy
API and excpients screening
Aim: Understanding impact of API and excipients characteristics and ratio on product performance
What we do:
- Selection of API
- Selection of excipients grade and ratio
- Define Lactose PSD
Manufacturing process development and optimization
Aim: Development and optimization of formulation processes through the understanding of the impact of process parameters on product performance
What we do:
- Technology selection between particle engineering (e.g. spray drying) or blending processes
- Manufacturing process optimization
- Filling process selection
- Filling process optimization
Primary and secondary packaging process development and evaluation
Aim: Development of a suitable packaging process and evaluation of the impact of packaging on product performance and stability
What we do:
- Support in device optimization
- packaging screening and evaluation
Scale-up and technology transfer
Aim: Studying the impact of scale-up on product performance
What we do:
- Scale-up studies
- Technology transfer
- PK study batches
- Process validation studies
- Support in manufacturing and release of clinical batches
Regulatory studies
Aim: Conduct studies based on requirements of relevant regulatory guidance
What we do:
- MC studies
- In-vitro BE studies
- Stability studies
Analytical method development and validation is an integral part of DPI development.
It is the process of developing, optimizing, and validating analytical methods to assess the quality and performance of the DPI formulation throughout its development and manufacturing stages. Using various analytical techniques, helps in characterizing the formulation, assessing its stability and performance, and ensuring compliance with regulatory requirements.
Throughout the development INTO is able to conduct the whole analytical development with robust and innovate process to accelerate your DPI development.
Raw materials and drug product method development & validation
Aim: Define and validate methods to characterize Critical Quality Attributes (CQAs)
What we do:
- As per pharmacopeia method development of all tests required for inhalation testing (including E&L, Foreign particulate matter etc)
- Defining control strategy through FMEA
RLD characterization
Aim: Define Quality Target Product Profile (QTTP)
What we do:
- In-depth RLD characterization
Formulation support
Aim: Define CQAa and CPPs. Understanding impact of process parameters on product performance
What we do:
- Device optimization
- Routine analysis for formulation development
In-vitro in-vivo correlations (IVIVC)
Aim: Use appropiate IVIVC techinque to accelerate development and avoid clinical trials
What we do:
- Selection of most appropriate IVIVC technique
- Validation of technique throughout the developemt
- Support to include the development of IVIVC within dossier
GMP release and stability
Aim: Release GMP materials
What we do:
- Specification setting
- GMP release of registration and clinical batches
- Informal and formal analysis of stability studies
Regulatory studies
Aim: Conduct studies based on requirements of relevant regulatory guidance
What we do:
- Support with regulatory strategy
- Support with deficiency letters
- CMC studies
- In-vitro support to clinical studies
- In-vitro BE studies- design of protocol and performance
- Statistical analysis of BE study
The multifaceted nature of Dry Powder Inhaler (DPI) formulations underscores the complexity involved in developing the final drug product. This process entails a synergistic interplay between the filling and blending platform and the specific API and Lactose in use. Moreover, considerations such as particle interaction and device compatibility must be thoroughly addressed.
In addition to the comprehensive services outlined, – encompassing analytical methods, API characterization, and full formulation development, – we extend an invitation for you to tap into our specialized expertise. Herewith, you have the option to request a consultation in one of the specific areas mentioned below, allowing for a preliminary exploration of your challenges on a targeted subject with the expert. It is important to note that this consultation will be conducted at a personalized, individual level if preferred.
Andrea Silvestri
asilvestri@sterling.it
Analytical Research Manager
Sterling
Area of expertise:
Particle engineering, Solid-state characterization, Analytical development
Maribel Bógalo
maribel.bogalo@dfepharma.com
Manager Development & Support
DFE Pharma
Area of expertise:
Analytical development, Formulation development, IVIVC techniques, Regulatory support
Marco Laackmann
marco.laackmann@hoefliger.de
Sales Director Inhalation Technology
Harro Höfliger
Area of expertise:
DPI development and feasibility assesment, DPI processing and device sourcing, Assessment of DPI product investments
Irene Rossi
irene.rossi@hoefliger.de
Consultant Inhalation Technology
Harro Höfliger
Area of expertise:
Formulation technologies for OINDP products, DPI processing and characterization, pre-formulation and formulation studies for large and small molecules
Our technical and scientific team is ready to support you.
Get in touch!
Maribel Bógalo
DFE Pharma
Irene Rossi
Harro Höfliger
Andrea Silvestri
Sterling
