Knowledge Hub

Sustainable formulation solutions for a cytotoxic small molecule: impossible? No! Partner with us to meet the increasing demand to use more environmentally friendly solvents!

As an expert in formulation and process development for small molecule drugs, we encounter many drugs that have solubility and stability issues and drug formulation development struggles i.a. with the following pain points: a) Finding an appropriate organic solvent / solvent mixture that can dissolve the API without compromising its stability, b) many organic solvents are toxic and regulatory agencies have strict limits on the permissible levels of residual solvents in pharmaceutical products, c) removing solvents to acceptable levels can be technically challenging and costly.
On top, there is increasing ecologic and social pressure to use greener, more sustainable solvent systems. Finding suitable alternatives to traditional organic solvents that are environmentally friendly can be difficult. Here at ProJect Pharmaceutics CRO we take on the challenge together with you, we are committed to using greener solvents wherever possible:

• careful selection of the least toxic & most effective solvent for the specific API
• using mixtures of solvents to enhance solubility & stability profiles
• utilizing advanced formulation techniques to minimize solvent use
• exploring greener solvent alternatives to reduce environmental impact and improve safety.

If you also want to partner with us to benefit from reduced toxicity, biodegradability, lower volatility and renewable sources when using greener solvents, contact us.

At ProJect Pharmaceutics, we specialize in conducting process-mock up studies prior to technology transfer to the designated contract manufacturing organization (CMO). In a process mock-up case study about “Adsorption of detergents (kinetics and amount) during sterile filtration”, the detergent content was monitored before and after the first and second round of sterile filtration. The result was identical: the detergent content decreased directly at the beginning of sterile filtration until the filter material was saturated and then reached the initial concentration towards the end of the filtration volume.
To avoid this, follow our expert tip on double sterile filtration:

• Either discard the first x mL of the compounded, detergent-containing solution, or
• Precondition the filter material with x mL of the mixed solution.

Determination of the theoretical (!) molar extinction coefficient by the amino acid sequence of a biomolecule is i.a. well known in pharmaceutical industry. However, according to ICHQ6 guidelines the theoretical value ought to be supported by an empirically (!) determined value for the drug product at least once.
At ProJect Pharmaceutics, we are able to determine the extinction coefficient experimentally using an absolute gravimetric determination approach. Thereby, we are able to consider not only the protein primary sequence but also glycosylation as part of the overall protein mass.
If you also need support determining the molar extinction coefficient of your biological product empirically, contact us.

Here at ProJect Pharmaceutics, we can monitor temperature kinetics & distribution during lyophilization (freezing, primary & secondary drying) using our contactless infrared (IR) thermal camera system. Monitoring drying kinetics during lyophilization can support evaluation of heat transfer into vial, confirmation of product temperature in vial and optimization of the overall freeze drying process.
Using the IR thermal camera system, we can also monitor the thawing kinetics in the drug substance batch and thus i.e. detect inhomogeneous thawing behavior in the drug substance bulk container or overall duration of the thawing process.
Curious? Then check out some videos on IR camera monitoring on our YouTube channel https://www.youtube.com/watch?v=lK1fszYFjD4

Has your CMO (contract manufacturing organization) also started yet rejecting customers who show up with day-long lyophilization cycles? As securing production slots becomes increasingly challenging in today’s competitive contract manufacturing landscape, this is likely to affect more and more customers who come in with an old-fashioned, multi-step and super conservative freeze-drying cycle.

At ProJect Pharmaceutics, we are specialized in determining modern freeze-drying cycle parameters in just five (!) rounds based on a smart and firm in-house algorithm for process and formulation.

A short and modern lyophilization cycle

• reduces parameters, enhances robustness and simplifies validation
• improves accessibility to CMOs
• drives down manufacturing expenses

Although one-step overnight cycles are one of our specialties, we understand that this might be too explorative for most clients. However, we are known for delivering shorter cycles than the market average. On top, we support the implementation at the commercial plant in communication with the CMO towards a seamless technology transfer.
If you also would like to find out whether you can save money on freeze-drying and shorten your lyo cycle to attractive conditions, contact us.

Are you sure your stopper is dry enough to be safe enough for your lyophilized drug product’s stability? Have you ever experienced increase in residual moisture content in your lyophilized drug product and could not explain why? Do you know the moisture uptake capacities & water release characteristics of your lyo stopper?

An increased residual moisture content could be caused by incomplete drying of the stopper after sterilization. Some stoppers feature a higher moisture uptake potential, weaker stopper drying kinetics and lower water release characteristics than others. Some stoppers are simply subjected to an inefficient drying process at the CMO – without anyone noticing.

Check out our “check your lyo stopper“ service offering:

You do not need to have a project running with us. You do not need to disclose your API nor any other details of your drug product. We simply need the sterilization and drying process protocol for your stoppers as performed at your CMO, and some stoppers (~ 100 pcs).
Our experts will conduct a comparative evaluation on your stoppers versus modern state-of-the-art stoppers and carefully evaluate stopper drying kinetics, moisture uptake potential & water release characteristic.
If you also want to find out whether you are already using a stopper that safeguards your lyo product, contact us.

Have you ever calculated direct and opportunity costs resulting from several day-long lyophilization cycles at your CMO?

Want to get easier a slot at your CMO with an optimized cycle?

Want to check your cycle for robustness prior transfer into GMP manufacturing?

Tired of burning money with day-long lyophilization cycles?

Longing for a slim, efficient, but robust lyo cycle?

Maybe even tough enough to go for a modern, single-step overnight cycle?

Check out our “check your lyo cycle“ service offering:

You do not need to have a project running with us. You do not need to disclose your API nor any other details of your drug product. We simply need lyophilization process parameters, a print out of an actual cycle, and some samples of drug product (2-3 vials).

Our experts will carefully analyze the data and identify any potential risk and process optimization:

• Product quality risk assessment
• Detection of technical weaknesses
• Scale-up risk assessment
• Potential product quality improvement
• Potential cycle length reduction

Even if one-step overnight cycles are one of our specialties, we understand that this might be too explorative for most clients. However, we are known to deliver shorter cycles than market average. If you also want to find out whether you can save money during lyophilization and shorten your lyo cycle to attractive conditions for CMOs, contact us.

Do you have a delicate molecule that is difficult to formulate and liposome encapsulation seems an elegant solution …but you fear the hurdles of processing towards grade A environment?

Partner with us on packing your API in liposomes made of GRAS-status phospholipids that overcome the common hurdles of processing a liposomal formulation. At ProJect Pharmaceutics we have developed an innovative process for the liposomal encapsulation of APIs and manufacturing of drug loaded, lyophilized liposomes. The process is cost efficient and GMP compatible, particularly addressing processability under aseptic conditions.

• High entrapment efficiency
• Compatible with biomolecules
• Charge modification
• SUVs (small unilamellar vesicles) for i.v. injection
• LMVs (large multi-lamellar vesicles) for s.c. depot

Have you ever tried to predict how long sublimation will take for the very first feasibility lyophilization cycle? Wouldn’t it be nice to anticipate primary drying time to not mess up this very important test lyophilization by choosing a too short time and end up with a wet product?

ProJect Pharmaceutics is specialized in lyophilization process development for injectables. One of our new customers, who did not know us yet, was very nervous once the project moved towards the first feasibility lyophilization cycle for his drug product on a Friday afternoon. He tried in approximate way to calculate a time that was not too conservative on the one hand, but also not too short on the other hand, in order to answer as many questions as possible in this first cycle. Pragmatic as our development team is, we offered to simply switch the cycle to secondary drying when primary drying was complete. He wondered how this might be possible over the weekend without shift operation. We disclosed that – thanks to modern PAT (process analytical technology) – we can control our freeze dryers from home and simply switch his cycle one step further on Sunday morning over a morning coffee. Instead of calculating, we simply test how long it takes.

Our customer was highly delighted with such simple pragmatism, which he hasn’t encountered yet in the pharmaceutical industry.