SpinSwiper.com

Questions & Answers

Why did we develop the SpinSwiper?

We developed the SpinSwiper to make microparticles more efficiently in large quantities. Most microparticle formulations currently under clinical use have been prepared by double emulsion methods. The SpinSwiper provides easier alternative ways of developing microparticle formulations using a microfabrication technique known as the hydrogel template method.

Advantages

What are the advantages of the SpinSwiper method?

Easy scale-up manufacturing of microparticles.

Easy sterilization of SpinSwiper for aseptic microparticle production.

Monodispersed microparticles in predetermined size and shape.

Predetermined size of microparticles ranging from 2 µm to 100 µm.

Preparation of microcapsules (i.e., the core-shell microparticles).

Ability to use polymer solution with high viscosity.

Multiple filling of micro-wells with different drug/polymer solution.

Use of various solvents with different boiling points and water solubilities.

Ability to control the drug release kinetics (including delayed release).

Method

What is the hydrogel template method?

The hydrogel template method is also called water-soluble polymer template or PVA template method. The overall process of the hydrogel template method is described in the figure below.

PVA template method

A silicon wafer master template A is prepared to have pillars with a diameter of 50 µm. The diameter here can be controlled to any specific value from 1.5 µm to 100 µm or larger. Usually, we make microparticles of 50 µm, because they are small enough for easy injection using common needles.

On top of the master template is added a solution of a water-soluble polymer that can form a gel or that can be dried to form a membrane B. Gelatin is used to form a hydrogel by lowering the temperature. Poly(vinyl alcohol) (PVA) is also used to make a tougher, more resilient and easy-to-handle polymer template.

(To preserve the silicon wafer master template, we also made a silicone rubber intermediate template for making hydrogel templates. In this case, the silicon wafer master template contains cavities instead of pillars.)

The gelatin or PVA template is peeled off the master template and then placed on a flat surface exposing the cavities C.

The cavities are filled with drug-PLGA mixture dissolved in organic solvent (e.g., dichloromethane, ethyl acetate or benzyl alcohol) D.

Various PLGA with different molecular weights and different L:G ratios can be used. The main advantage of the hydrogel/polymer template method is in the easy collection of the microparticles formed in the template. Microparticles are released from the template by simply dissolving the templates in water E.

The released microparticles can be washed and collected by centrifuging or filtering though fine meshes F.

PVA ProtocolPDF

The Blade

How does the blade fill micro-wells in a PVA template?
cross sections

SpinSwiper's “blade” provides a metered flow of drug/polymer solution to the wells in the template. This increases reproducibility.

Videos

Are there videos showing how to use the SpinSwiper?

Yes, please click below to start the video instruction.

The procedure of using SpinSwiper consists of several steps as shown in the figure below. First a PVA template is placed on top of the rubber disk A. The rubber disk is shown in orange in the figure. The rubber disk is in turn secured on an aluminum plate (backing plate). The whole platter is placed on the rotating plate (or turntable) of the SpinSwiper B. Then, the drug/polymer solution is filled inside a syringe and then placed on a syringe pump C. The blade is then connected to the tubing from the syringe pump D, and placed on the lower crossbar and the latch is closed E. The blade is lowered by rotating the knob at the top of the arm F. Then the syringe pump is started to introduce the solution to the blade and swiping is started by rotating the plate G. At the completion of the filling process, the upper assembly is raised to remove the template H. The SpinSwiper is designed to make the microparticle fabrication process as simple as possible. video sequence

Microparticles

What do the microparticles produced by the hydrogel template method look like?

The hydrogel template method (water-soluble polymer template or PVA template method) produces microparticles that have predetermined size and shape. The microparticle shape can range from disc to hollow shell, and the size can vary from 2 µm to 50 µm or larger. The following are some examples of microparticles produced by the method

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Polymers
What types of polymers are commonly used to make microparticles?

Microparticles can be made using a variety of polymers, both synthetic and natural. But we make microparticles to deliver drugs for extended periods of time ranging from weeks to months after subcutaneous or intramuscular administration. For practical reasons, biodegradable polymers are used to make microparticles. The most commonly used biodegradable polymers are poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and poly(ε-caprolactone) (PCL).

Many biodegradable polymers with different molecular weights and compositions are available at Polyscitech (polyscitech.com).

Microfabrication

What is microfabrication (or nanofabrication)?

Microfabrication is the process of making objects of micrometer sizes. (Naturally, nanofabrication is the process of making nanoscale objects). Several microfabrication techniques have been developed to make microparticles for drug delivery applications. They include:

  1. Microimprint lithography
  2. Solvent assisted micromolding
  3. Micro fluid contact printing
  4. Micro contact hot printing
  5. Step and flash imprint lithography
  6. Particle replication in nonwetting template
  7. Hydrogel template method

Suitable

Are the microfabrication techniques suitable for making microparticles for drug delivery?

Any microfabrication technique can be used to make drug-containing microparticles. But if the goal of making microparticles is to develop formulations that can ultimately be used in clinical applications, i.e., in humans, then the following factors need to be considered.

  1. Does the process involve any component that cannot be used in humans?
  2. Is it possible to remove any impurities without losing the loaded drug?
  3. Is the manufacturing process reproducible?
  4. Is it possible to control the drug release kinetics?
  5. Can a laboratory prototype device be extended to scale-up production?
  6. Is the cost of manufacturing low enough to be practical?

Products

What are microparticle products currently on the market?

There are about two dozens of implantable extended release formulations. The majority of them are based on biodegradable PLGA polymers. The examples are shown below.

Zoladex 3-month 10.8 mg DEOPT goserelin acetate implant 1, 3 months SI 1989; Lupron Depot leuprolide acetate for depot suspension 1-4 momths MP 1989; Sandostatin LAR Depot (octreotide acetate for injectable suspension) 1 month MP 1998; Trelstar (triptorelin pamoate for injectable suspension 1 monnth MP 2000 6 months MP 2010

What are microparticle products currently on the market? (continued)

Suprefact Depot 9.45 mg implantat Buserelin acetate (Rod) 2, 3 months SI 2000; Somatuline Depot (lanreotide) injection 1 month MP 2000; Arestin minocycline HCl 1mg microspheres 2 weeks MP 2001; Eliaard (leuproide acetate for injectable suspension) 1,,2,4,6 months IS 2002
Risperdal CONSTA risperidone long-actin injection 2 weeks MP 2003; Vivitrol (naltrexone for extended-release injectable suspension) 1 month MP 2006; Ozurdex (dexamethasone intravitreal implant) 0.7 mg 3 months SI 2009; once-weekly ByDureon exenalide extended-reelease for injectable suspension 1 week MP 2012

Generic

Can the SpinSwiper be used to make generic microparticle products?

The first PLGA-based extended release formulations for clinical use were introduced in the late 1980s. Since then, only a dozen of the PLGA microparticle formulations have been developed. This small number is in stark contrast with thousands of sustained release formulations developed for oral administration. One of the reasons for such a small number of PLGA microparticle formulations may be that conventional methods of PLGA microparticle preparation have not been easy in scale-up manufacturing as well as controlling the drug release kinetics.

The SpinSwiper allows researchers to design and produce microparticle formulations fast in quantities large enough for in vitro characterization and in vivo studies. A PLGA formulation can be adjusted easily to obtain the desired release kinetics matching that of a clinical product.

Why