Formulation & Drug Delivery Technologies

Drug product formulation is at the core of Particle Sciences. Industry-wide, delivery of active pharmaceutical ingredients (APIs) has taken center stage along with the API's themselves. Focused initially on problematic new chemical entities (NCEs), delivery systems are now the go-to approach for both NCE commercialization and the refinement and repurposing of existing APIs. The biological and chemical needs generally fall into one or a combination of a small number of categories. In addition to physicochemical and physiologic goals, business concerns also drive the use of sophisticated drug delivery systems. Intellectual property, life-cycle management, cost and market differentiation are examples.

While on the surface, the issues are daunting, there are common fundamental properties that drive real-world possibilities. Compounding the difficulty in establishing a decision tree is the fact that there are myriad drug deliver approaches being touted by a large number of formulation companies. In reality however, there are a limited number of technologies that are currently truly commercially viable.

At Particle Sciences, we view our role as helping our clients identify and execute the commercial development plan that best suits their needs taking into consideration all aspects of their specific situation from API properties, to commercial opportunity to intellectual property.

We are the partners of choice for so many because Particle Sciences offers an integrated services and solutions package to streamline development and minimize risk. Our facilities are extremely well equipped, cGLP/cGMP compliant, FDA registered and we are licensed for all DEA scheduled compounds. From small molecules to biologics to highly potent compounds, Particle Sciences has the experience and infrastructure to get the job done.

Formulation

Particle Sciences believes formulation is a data driven science and we follow a methodical efficient approach. After the client's needs are thoroughly understood and the target product profile (TPP) defined, a well-established product development algorithm begins. Starting with DOSE™, our own preformulation system and proceeding through formulation, production for pre-clinical toxicology, scale up and clinical trial material production, Particle Sciences is expert at efficiently getting our clients to commercializable products.

Particle Sciences has a great deal of successful experience in the development of successful delivery systems for many types of APIs and sites of action. Since 1991, we have been designing liquid, suspension, powder, solid solution, semisolid formulations and even drug eluting devices. From drug nanoparticles to multiphasic emulsions to solid lipid nanoparticles Particle Sciences has, on behalf of its clients, created many new commercialized products. Utilizing a number of approaches, we specialize in BCS II/III/IV molecules and can work with the most difficult to formulate APIs to maximize their bioavailablity and stability.

Throughout the process Particle Sciences incorporates a Quality by Design (QBD) approach using modeling and Design of Experiments (DoE) to arrive at the best product with the strongest regulatory package.

Particle Sciences has been at the forefront of drug delivery and has learned first-hand that no single approach solves all problems. Our strategy is to be expert at a number of technologies specifically designed to address the common problems in drug product formulation. To accomplish this we have both developed technologies in-house and in-licensed others where appropriate. Each of the technologies we work with has application across two or more dosage forms and multiple routes of administration. Of course, we have all the analytic and production support needed to advance these products into the clinic.

Particle Sciences uses standard approaches such as liquids, suspensions, extended and controlled release polymers, emulsions, self-emulsifying systems and a host of others. In addition, we have a collection of advanced systems. A few of Particle Sciences' technologies are listed and briefly described below. Please contact us to discuss your specific goal.

  • Nanoparticles: With uses ranging from increasing bioavailability of poorly soluble APIs, to formulating parenteral products to tumor targeting, nanoparticles are now a standard drug delivery option. Particle Sciences is the nano-technology expert with decades of experience and a full range of equipment for dry and wet milling, nano-precipitation, nanoparticle formulation and nanoparticle surface modification.
  • Encapsulation: Employed to protect a given API, taste mask or to facilitate targeted delivery, encapsulation is a proven approach that Particle Sciences has been practicing for over 20 years.
  • Hot Melt Extrusion: Equipped with a range of single-screw and twin-screw pharmaceutical extruders of various scales, Particle Sciences uses this approach for both solid oral dosage forms and drug eluting devices. Combined with our DOSE™ system to quickly hone in on the right polymer choice, HME is an excellent path to increased bioavailability.
  • DOSE™: Particle Sciences has developed a proprietary approach to solubilization using a combination of computational tools and empirical data. DOSE has resulted in several clinical products already and is the basis for much of our work.
  • Nanoparticle Complexation: Used to modify small and large molecule delivery by associating the API with a controlled nano-particle. Particle Sciences has an established special expertise in this emerging field.
  • High Pressure Homogenization: When fine particles or highly uniform emulsions are key to performance, high pressure homogenization is an excellent option. At Particle Sciences we use Microfluidics'® homogenizers to accomplish this. We have capabilities that span early development to sterile cGMPclinical supply.
  • Drug Milling: Particle size reduction is a common unit operation in pharmaceutical formulation. Reasons range from improving homogeneity and dose uniformity to increasing bioavailability to making drug products suitable for parenteral delivery. Particle Sciences has the complete set of milling technologies in-house including jet, ball and high energy milling (Netzsch® and Dyno®-Mill). We can mill highly potent compounds and can also mill aseptically.
  • Solid Solutions: Used to modify bioavailability, solid solutions are another go-to technology. Particle Sciences offers several systems for preparing solid solutions including Hot Melt Extrusion and spray drying.
  • Solumer®: A patented spray drying technology in-licensed from SoluBest that has been shown in human trials to increase bioavailability through careful control of size and crystalinity of the API.
  • PEGPLUS™, Pegylation,: Using commercially available PEG's or our own proprietary cationic PEGylation agent, PEGPLUS™, we are able to impact a host of API properties from half-life to toxicity. Using the PEGPLUS system, we can gain all the advantages of PEGylation without creating a new chemical entity. The system is used to apply cationic polymer compositions to pharmaceutical and medical device apparatuses. Also under the system, general pharmaceutical drug development services are offered in connection the application process.
  • LyoCell®: This in-licensed technology combines a lipid based approach with nanoparticles. Leveraging the power of reverse cubic phase geometry, the hydrophobic and hydrophilic domains in these nanoparticles are never more than a few nanometers apart giving the particles unique solubilization properties. The technology uses GRAS ingredients and is useful in virtually every dosage form.
  • Solid Lipid Nanoparticles (SLNPs): Used to increase the solubility of a given API and to enhance delivery, SLNPs are a versatile and proven approach. Particle Sciences has been mass producing SLNPs for over 15 years.
  • Injection Molding: Used to mold the final form factor of a drug eluting device, injection molding is one of two approaches Particle Sciences uses to manufacture devices. As a leader in medical device injection molding, we are fully equipped with a variety of machines covering the entire development path.

Partial Equipment List

  • Class 10,000 (ISO 7) through 100 (ISO 5) Cleanroom
  • Sterile laminar flow hoods
  • Silverson L4RT-A laboratory homogenizer with in-line capability
  • Ad-mix Benchmix OPLB-300 Rotosolver
  • Three Ultrasonic 500W dispersers/homogenizers with in-line capability
  • Netzsch Labstar LS1 media mill
  • Two Premier PLM-1.5 liter jacketed double planetary mixer with vacuum
  • Two Buchi B-290 Mini-spray dryers with organic solvent capability
  • Multiple Sturtevant Qualification Micronizers with sanitary collector capability
  • Roller mills
  • Buchi Encapsulator B-390
  • Netzsch DeltaVita┬« 15-300
  • Coatema┬« EasyCoater
  • Millrock Max Series with VHP sterilization
  • Dri-Air Industries NAFM Nitrogen Dryer with RH 15 (15lb) Hopper
  • Gaulin 15MR laboratory homogenizer
  • Lyophilizers
  • Watersep bench-scale tangential flow filtration unit
  • Glass-lined jacketed and pressurized reactor
  • Cooling tower with 2 heat exchangers
  • Nissei 22-ton injection molder
  • 3-ton bench scale injection molder
  • Haake 9000 torque rheometer with twin screw extruderUSP water treatment system
  • Multiple Stability Chambers
  • Autoclave
  • Fill Integrity Tester
  • M-110EH-30 Basic BioPharma Microfluidizer
  • Semi-automated film and coating
  • PlasticWeld HPS-20 Ring Bonding Machine and PlasticWeld HP-EM Single Purpose Tip Forming Machine
  • Extruline 13xy Dual Axis Laser Micrometer
  • ConAir CPC 1-12/CSC-.25L-SD Medline Puller-Cutter