We developed the SpinSwiper to makemore 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 technique known as the
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.
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.
SpinSwiper's “blade” provides a metered flow of drug/polymer solution to the wells in the template. This increases reproducibility.
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The(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 (Akina’s current capabilities are 50 µm microparticles). The following are some examples of microparticles produced by the method
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 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:
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.
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.
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.