Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals

The overall goal of this procedure is to assemble a disposable aerosol dispersion system for use in dry powder aerosol development and evaluation. This technique addresses key questions in pharmaceutics and aerosol science with respect to the delivery of dry powder aerosols of importance to pharmacokinetics and also efficacy testing, and it currently meets an unmet need. The main advantage of this technique is that it uses Dosators that are made from readily available materials and those materials are fairly economic.

One serious advantage is that they can be used in a hazardous environment because the materials themselves are disposable. Begin by perforating the bottom of a 0.5 milliliter polypropylene microcentrifuge tube with a one to two milliliter diameter hole. Next, use a number 22 drill bit to create an approximately four millimeter diameter hole in the center of the microcentrifuge cap.

Punch out a 60 by 60 millimeter mesh with a 0.0045 inch wire diameter screen and a five millimeter outer diameter from a 304 stainless steel wire cloth and use the end of a blunt tip needle to insert the screen into the bottom of the microcentrifuge tube so that it covers the perforation. Then, press fit the narrow end of the microcentrifuge tube tip into the end of the needle with enough pressure to adhere the tube tip to the needle without cracking the plastic, and use ethanol to gently clean the top of the needle and the bottom of the tube. Assembling the Dosator while it is still wet, assist in achieving a tight fit Although the materials can also be wrapped with lab film after mating to provide additional stability as necessary.

After tearing an analytical microbalance, load the powder into the Dosator and use a forceps to plug the top of the microcentrifuge tube with cotton. Next, close the microcentrifuge tube cap and draw back a syringe plunger to the appropriate volume according to the specific experimental application. Then, insert the syringe into the back end of the Dosator with the needle end of the Dosator in the dosing port of the exposure chamber, and depress the plunger forcefully to expel the powder out of the device into the chamber.

The dosing chamber can be assembled from acrylic with a three inch long, four inch diameter central aerosol compartment, and tapered nose cones for evaluation of the aerosol exposure by passive inhalation. In this representative experiment, a spray dried drug powder of a mass median aerodynamic diameter of 2.9 micrometers was administered to guinea pigs in a dosing chamber using the delivery technique as demonstrated. Five 10 milligram doses of powder given at three minute intervals resulted in a maximum plasma concentration of five micrograms per milliliter, a similar concentration to that observed for endotracheal administration of one milligram per kilogram of powder by standard methods, indicating that the dosing chamber powder delivery is an efficient means of dispersion to the primary particle size.

Once used to the method, the Dosator assembly and filling can be accomplished in approximately five minutes if performed properly. After its development, this technique allowed researchers in the field of pulmonary drug delivery to explore novel tuberculosis therapies in a guinea pig model of disease. After watching this video, you should have a good understanding of how to build disposable Dosators for the dispersion of engineered dry powder aerosols.

Don't forget that working with some types of machinery can be hazardous, and precautions such as wearing safety glasses should always be taken when working with these materials.