Excipient Selection for Successful Formulation Development of Modified Release Oral Solid Dosage Forms
Modified release dosage forms offer numerous benefits, but formulation and manufacturing are notoriously challenging and require highly specialized pharmaceutical development skills. This is the second part of our blog on planning and execution of successful modified release oral solid dosage formulations. If you haven’t already, read Part I here.
In pharmaceutical manufacturing, once the required release profile of the API(s), its physicochemical characteristics, and the delivery system are all known, release-controlling polymers must be selected. The industry offers a multitude of options for tailoring where and how fast your APIs are released, as well as for enhancing manufacturability.
There are many release-controlling agents available: organic, water-soluble hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC); the enteric coating methacrylate; polyacrylic acids; polyethylene oxide, and so on. When looking to target a specific release rate, many aspects of the release-controlling polymer under consideration should be carefully examined, such as:
- Molecular weight— An increase in molecular weight generally slows the release profile.
- pH dependency — Release-controlling polymers that dissolve at specific pHs at a variety of rates allow formulators to select where in the GI tract release will occur
- Processability — Melting point, flowability, and compactability must be considered as they may affect processing; particle size analysis provides clues.
Other beneficial excipients
Additional consideration should be given to other excipients that are not predominantly release-rate-controlling but could potentially contribute to the manner the drug will release from the dosage form. These can be used in the formulation to improve processing characteristics for tablet manufacturers or impart other desirable attributes:
- Flow-enhancing excipients can ease processing
- Soluble or insoluble fillers may speed or slow release
- Disintegrants can hasten release
- Hydrophobic lubricants that aid in ejection of tablets after compression may slow dissolution
- Film coatings for tablets may also affect release rates:
Excipients affect both release rate and processability and can be selected to enhance or offset API effects and improve a formulation’s processing characteristics and dissolution performance. Note that a variety of excipients can have unintended effects on release rates.
Finding a pharma CDMO partner that will get your product right
Achieving a desired release profile and selecting the right excipients for modified release oral solid dosage formulation is complicated. Successful development with process optimization requires a holistic understanding of:
- Desired PK profile
- Dosing regimen
- API characteristics
- Processing considerations
- Appropriate excipient selection
In a consistent dosage form, these elements must all work together.
Recro scientists share decades of experience in modified release technology, as pioneers in this field since the 1980s. With an extensive history of manufacturing modified release dosage forms, our development and commercial teams are ready to leverage their keen insights and offer solutions to advance your project. With right-sized, proactive management, a proven track record of tackling the most complex formulations, and unparalleled regulatory expertise, our scientists will get your modified release formulation right.