A critical need currently exists in the pharmaceutical market for microparticles that can accurately and effectively control the release of poorly water-soluble compounds. Although these poorly water-soluble drugs are projected to have high clinical efficacy, they are often rejected in the early stages of research because of the high cost and technical difficulties of formulating and delivering molecules with poor water-solubility. Orbis Biosciences' novel Precision Particle Fabrication (PPF) technology has the potential to address this drug formulation dilemma by allowing flexible, cost-effective, single-step encapsulation of poorly water- soluble drugs, while also providing precise control over particle size, shape, composition, and release profiles. Our long-term goal is the application of a commercial-scale multi-nozzle PPF system for the production of drug-loaded particles with precisely engineered physical characteristics. Under SBIR Phase I Lab-to-Marketplace funding, we designed and optimized a multi-nozzle unit consisting of 12 individual nozzles capable of producing uniform, poorly water-soluble drug-containing microparticles of defined size and release characteristics. With this multi-nozzle unit design, we succeeded in our Phase I goal of establishing the feasibility of improving PPF production rate for encapsulation of poorly soluble drugs. The objective of this SBIR Phase II proposal is to incorporate 4 of these multi-nozzle units into a cGMP-ready, electronically controlled and monitored PPF processing device that will be capable of producing homogenously distributed 100 mm microparticles at a pilot scale production rate of 1 kg/hr and will be compatible with poorly water-soluble drugs. We will design, assemble, and fully test the mechanical subsystems of this PPF system (Aim 1). In parallel, we will also design, assemble, and test a fully integrated electrical system with a graphical user interface (GUI) that will control the mechanical subsystems and regulate key process parameters, including critical temperatures and pressures (Aim 2). Finally, we will integrate the mechanical and electrical components and optimize the system to achieve target performance metrics and particle specifications (Aim 3). Development of such a system will demonstrate the feasibility of scaling the multi-nozzle PPF system for full commercial scale production and derisk outside investment in the technology thereby enabling companies to partner in the co-development of PPF-enabled products. This proposal lays the groundwork for a platform to produce aseptic (but non-sterile) drug intermediates with release rates determined by the design of the microparticles themselves, not the final dosage format; thus, they may be processed into a variety of oral delivery formats without altering the drug release characteristics. This enables large degree of format flexibility in the development of pharmaceutical products - minimizing development costs and improving patient compliance.
Poorly water-soluble drug molecules are often rejected in the early stages of research and development, even when they are projected to have high clinical efficacy, because of the high cost and technical difficulties involved in the formulation and manufacture of effective drug delivery systems. Orbis Biosciences' novel Precision Particle Fabrication (PPF) technology has the potential to allow flexible, cost- effective, scalable, single step encapsulation of these poorly soluble drugs, while also providing precise control over particle size, shape, composition, and drug release profiles. PPF's level of control over a particle's physical characteristics enables the design of more effective drug delivery systems with precisely controlled release, better bioavailability, improved palatability, and greater formulation flexibility to address needs within the clinical space and the commercial market.