A large US company is looking for proposals for a manufacturing process that results in a stable and sterile injectable suspension or solution formulation of a hydrophibic water-insoluble drug in an aqueous solvent system which contains a second, hydrophobic drug.

They are interested in contract manufacturing, supplier agreement, proof of concept leading to scale up to manufacturing, joint development.

Description

The company has developed a promising drug yet does not have the in-house capacities to rapidly put together the various ingredients into a stable formulation. Possible approaches might include, but are not limited to:

• Encapsulation techniques
• Biodegradable microspheres
• Nano-coating of compounds
• Methods to obtain sterile or sterilizable fine suspensions of hydrophobic drugs in water.

The following approaches are not of interest:

• Solutions that use denaturating organic solvents or excessive heating steps
• Wet (sand, pearl) milling of the hydrophobic drug in the aqueous nano-sized suspension of the dextran drug.

Technical Specifications / Specific technical requirements of the request

The successful technology will:

• Provide a formulation that is stable for at least 2 and preferably 3 years at storage temperatures between 5 and 30 °C
• Not show aggregation or formation of a dense sediment
• Have a pH range from 5 to 8
• Be injectable and pass through a 21 gauge needle (e.g. suspended particle size d(90) <10µm)
• Arrive intact in the body and be well-tolerated in vivo
• Leave no residues near the injection point (biodegradable, biorodable or bioabsorbable injection)
• Be chemically and physically stable (non reactive with formulation components)
• Avoid incorporation of pharmaceutically unacceptable or potentially toxic substances like NMP, Dimethylacetamide and the like. Smaller amounts of DMSO may be acceptable. The formulation may include all types of pharmaceutically acceptable, i.e.non-toxic excipients, in particular surfactants, dispersants, hydrocolloids to stabilize suspended drug particles and also additives like preservatives, antioxydants, anti-freeze and foam reducing agents
• Be applicable on an industrial scale
• Minimum batch size of 1 m³
• Production capacity of 20 m³ per annum
• Cost effective
• GMP manufacturing standards.

The main components are:

• A small hydrophobic organic molecule that Is water insoluble at acidic or neutral pH and soluble yet unstable at higher pH In also insoluble in organic solvents and oils, except in polar aprotic solvents
• A large hydrophilic organic dextran based molecule that
• Is present as a colloidal solution in the aqueous continuous phase
• Is not soluble in oil and does not sustain the presence of larger amounts of organic solvents or oils (polar aprotic solvents may be tolerated to a small amount)
• Is stable at pH of 5 to 8
• Cannot be heated above 70°C.

Further Information (Technical Details Concerning the Profile)

The respondent should start by submitting a written response briefly describing the technical approach and providing information on technology performance, background, and description of the responding team and its related experience.

The response will be evaluated according to the following criteria:

• Overall scientific and technical merit of the proposed approach.
• Approach to proof of concept and performance.
• Potential for proprietary position (i.e. novel or protectable technology).
• Economic potential of the concept.
• The respondent’s capabilities and related experience.
• Realism of the proposed plan and cost estimates.

Some items that will be especially important to include:

• A non confidential description of the proposed technology, capabilities, expertise and/or products
• Process and material cost estimates
• Safety and/or toxicity data
• Stage of development of the technology
• Information on any intellectual property and existing/pending patents
• Preferred business agreements.

Collaboration Type

• Joint further development
• Testing of new applications
• Absolutely novel process

Responses from companies (large or small, startups, etc.), hospital or academic researchers, contract research institutes, pharmacologists, nutritionists, medicinal chemists, drug formulators, biochemists, physiologists, alternative or traditional medicine providers, etc., from around the world are all welcome.

Phase 1 – proof of concept

In vitro and in vivo laboratory testing is foreseen as well as informal accelerated stability testing. Initial cost evaluations will also be an important deliverable.

Phase 2 – final formulation and process development

Scale-up trials including and further assessment of commercial feasibility of the process.

Criteria for moving from phase 1 to phase 2

Successful demonstration of a stable drug formulation and a positive business case for the further development of the process.

Ref: 11 LU 87GA 3MS7