Drug Formulation Development
Our Formulation Development & Manufacturing Process
Formulation development is essential for optimising drug performance, ensuring patient safety and compliance, and meeting regulatory requirements in the pharmaceutical industry. It is a critical aspect of the drug development process that requires interdisciplinary expertise in pharmaceutical sciences, chemistry, engineering, and regulatory affairs.
PharmSky Research can help turn your drug into an effective formulation that meets patient needs and provides the intended product performance. From beginning to end we follow the ICH Q8, 9 and 10 guidelines, to ensure delivery of a robust product and a manufacturing process which performs consistently and meets all suggested requirements for 3.2.P.2 and 3.2.P.3 submission. This can include the following stages:
Rapid Formulation Development for FIH Trial
Working closely with the client, we will develop a target product profile (TPP) that meets their requirements. By carefully considering all available information, we will identify the most promising formulation options and produce laboratory batches to obtain stability data. Stable lab batches appropriate for pre-clinical studies and pilot scale batches suitable for First-in-Human (FIH) clinical trials can then be manufactured.
Based on stability data of up to 4 weeks or as required by the client, PharmSky can produce, label, and pack clinical trial material (CTM) in our phase I facility. We can then ship to the FIH clinical sites as per the client’s instructions. PharmSky has the ability, skills, and quality systems to support rapid formulation development for FIH trials. We will meet your requirements and efficiently deliver your FIH trial material on a swift timeline.
Being able to quickly assess the safety and viability of a drug in humans is often critical to the prospects of early-stage development companies. Providing a drug formulation that suitably enables this assessment is just as critical and can be the difference between trial success and failure.
Formulation Optimisation
PharmSky provides formulation optimisation services for clinical trials and potential commercial products. After completion of a FIH trial, in alignment with the client’s feedback, PharmSky will consider the critical quality attributes (CQA) of the product concerning the TPP. Based on these attributes, we will work towards optimising the overall design of the formulation, aiming to improve the stability of the formulation such that is suitable for later clinical phase I, II, or III trials. Utilising Quality by Design (QbD) tools such as Design of Experiments (DoE), we can conduct multivariate screening and optimisation studies to identify the most important material attributes and process parameters and ensure readiness for further scale-up.
During this stage, PharmSky can source systems suitable for the client’s needs and initiate stability studies in these containers/closures to ensure compatibility and verify that there will not be extractable and leachable concerns. The extent of this stage can be tapered depending on the client’s requirements.
The right formulation provides a drug with the stability and attributes required to be safely administered. By following a Quality by Design formulation optimisation approach, PharmSky’s scientists are able to provide a high quality product from the outset, avoiding the need for potentially costly rework.
Scale Up and Technology Transfer
As the product moves towards later stage clinical or commercial manufacture we can work with the client and their proposed manufacturing site to scale up and transfer the manufacturing process. The entire product life cycle can be risk assessed and a viable formulation and manufacturing design space established to ensure the process repeatably produces a robust finished product. The data generated at PharmSky from process development, scale up and tech transfer can be used for your final product registration if required.
The ability to scale up a manufacturing process from lab-scale to manufacturing-scale is critical to the viabiltiy of a drug product Mistakes made in early stage development can quickly snowball, preventing successful technology transfer to a manufacturing site and potentially adding years to the product development cycle.
Types of Dosage Formulation
Selecting the right dosage form can increase drug stability and shelf life, simplify storage, handling, and administration requirements, modify behaviour upon administration, and provide commercial advantages against competitors’ products. PharmSky Research specialises in developing formulations for a wide range of dosage and delivery forms including the following:
PharmSky scientists have decades of experience in development and registration of both simple and complex aqueous and non-aqueous sterile injectables for global markets. This includes lyophilised formulations and the associated process development.
We understand the complex regulatory space sterile injectables inhabit and will help you carefully navigate this space to ensure production of a stable product.
Challenges commonly encountered in injectable formulation development include meeting concentration and solubility requirements, water insoluble drug substances, drug substance susceptibility to oxidation, hydrolysis or photodegradation , container closure selection and leaching from such, particulate matter contamination, scale up, in-use stability and sterilisation method identification. If you need assistance in any of these areas, PharmSky will be able to help you.
Developing a viable sterile injectable product is a balancing act, where a products chemical and physical stability, excipient safety and manufacturing cost all need to be carefully considered. Therefore, having experienced development scientists involved is critical.
Difficulties confronted in topical formulation development include ensuring adequate skin permeation, formulation stability, irritation/sensitisation caused by excipients, dosage uniformity and preservative selection. Following our formulation development processes, we will help you overcome these and ensure that ideal excipient combinations are selected to produce a stable, efficacious product, be it a cream, ointment or gel. We can also work with you to develop suitable analytical methods to assess skin permeation and chemical, physical and microbiological stability.
Topical formulations are designed to deliver a drug through the skin. Understanding how the skin functions as a barrier enables the development of an effective formulation which can take advantage of this organs natural properties.
Nanoparticle formulations such as liquid emulsions, liposomes and polymeric and lipid nanoparticles can help overcome solubility, toxicity and degradation issues. However, developing formulations of this type is fraught with risk. The added complexity can quickly lead to stability, scale-up and/or regulatory issues. To avoid these, it is best to work with a company experienced in navigating these challenges such as PharmSky.
Up to 90% of drugs in the development phase and 40% of marketed products exhibit poor aqueous solubility. Therefore, the ability to successfully develop formulations for poorly water-soluble drugs has become essential. Many newly proposed or investigational drugs suffer from water solubility issues, presenting major hurdles to the design of suitable formulations that can be safely administered to patients.
At PharmSky, we have years of experience in the development of techniques and formulations to overcome aqueous solubility hurdles. We can help you develop formulation strategies for hydrophobic drugs, with options such as the use of liposomal formulations, cyclodextrin carriers, solid lipid nanoparticles, nano or microemulsions and co-solvent systems considered. Completion of pre-formulation studies including solubility studies and solid-state characterization of API can be used to support formulation development. Our team are also experienced in scaling up and addressing the regulatory issues associated with hydrophobic drug formulations and delivery systems.
Nanoemulsion offers great potential and flexibility for drug product development. PharmSky’s advanced Pharmaceutical Nanoemulsion Development Platform offers holistic service, helping you bring complex nanoemulsion products from concept to market-ready success.
See our Pharmaceutical Nanoemulsion Development Platform capacity for more information.
Depot formulations are used to prolong the release of an active compound, thereby reducing the frequency of dosing and improving patient compliance. If you have a product that would benefit from this, PharmSky can recommend and test a range of different gelling and/or particulate options to meet your desired target product profile. We are experienced in overcoming the complexities of this process, designing robust formulations, and developing models for drug in vitro/in vivo release to understand product behaviour following injection.
Depot formulations expand a drug’s potential applications by providing a mechanism through which pharmacokinetic behaviour can be modulated. However with opportunity comes risk, making careful product development critical.
From simple generic copies of existing formulations to complex products which improve upon these by utilising the technologies above, PharmSky can help you bring a high-quality generic to market quickly and safely. If you have a generic you want to develop, get in touch and we can explore your options.
Generic medicines are direct copies of existing products developed to provide patients with cheaper alternatives. They don’t have to be limited to this however, with the development of safer or more-user friendly formulations possible with the right development team. For more information see our solutions for Complex Generic Development.
Why Choose PharmSky To Partner With?
Experience is crucial in formulation development, and PharmSky’s scientists bring decades of expertise to our clients. Combining this experience with our clients’ insights and our deep understanding of manufacturing and regulatory requirements, we create safe and effective formulations that maximise the clinical and commercial potential of their products. We embrace challenges, leveraging the diverse backgrounds of our staff to explore solutions others might overlook.
With our team’s academic and industry expertise spanning cutting-edge chemistry, biology, nanotechnology, and complex food sciences, innovative solutions are always within reach. Above all, we prioritise our clients’ needs, maintaining honest and transparent communication as our top priority.
Contact Us Today
Fast track your development with our extensive services. Get in touch so we can discuss your requirements.
Send Us a Message
And we’ll get back to you shortly.
Frequently Asked Questions
Formulation development is the process of designing a formulation (combination of excipients) that will allow a drug substance (active ingredient) to maintain its pharmaceutical and microbiological quality upon storage enabling safe and efficacious administration at any time within its listed shelf life. Development studies are completed to identify an appropriate formulation and to monitor its stability over time. It is a part of pharmaceutical development which also includes analytical method development and validation and manufacturing process development.
Typically, companies aim to complete early stage trials as quickly and as early as possible to verify the potential of their pre-clinical candidate/s. Therefore, formulation development should be directed to support this. A formulation needs to be stable across the life of the trial, safe for administration to the patient and deliver the drug such that it is biologically available.
Several alternative models are also being used more frequently in recent times. One approach is to prepare the formulation directly prior to administration, meaning stability only needs to be demonstrated over a 24-48 hour period. Where the impact of the formulation is unclear, a rapid screening approach may be used where mutiple formulations are prepared in advance or on demand concurrent with the trial. Each formulation is trialed to identify the one which can provide the optimal safety/pharmacokinietic profile. PharmSky’s flexible team can support and work with you to support whichever model best suits your needs.
Different approaches are used depending on the complexity of the formulation and potential manufacturing process. All formulation development activities are completed following the ICH Q8 guideline recommendations. Studies that may be considered include solubility screens, formulation screens and fomulation optimisation studies. the latter will often include a Design of Experiment component intended to understand formulation robustness towards the development of a design space. Throughout development, the products quality target product profile directs the identification of critical quality attributes, and as development progresses, material attributes and process parameters. Risk assessment tools in line with ICH Q9 are used throughout the development to ensure all critical risks are controlled and a robust formulation and manufacturing process are developed.
When there are problems with the existing drug substance or formulation that cannot be overcome with more simple formulations. Or when the potential benefits (link to complex and differentiated generic development) of the complex formulation outweigh the additional development and manufacturing costs. In general, the simpler the formulation the better as the development time and manufacturing capital and operating costs will all be reduced.
If you think your product would benefit from a more complex formulation, its best to speak to a company which specialises in these. Feel free to contact our expert team today!
