Formulation Development
The aim of the pharmaceutical development was to manufacture three Dry powder Inhalation (DPI) formulations containing Fluticasone Propionate in an Plastiape Monodose DPI device, which provide distinct in vitro deposition patterns on a Next Generation Impactor. NGI is a high performance cascade impactor used to characterize aerosol particles by particle size. It is desirable to develop three formulations with the same emitted dose (ED), impactor size mass (ISM) but different mass median aerodynamic diameter (MMAD). Meeting these design criteria for the formulations would help to see if pharmacokinetic parameters are sensitive to regional differences in drug deposition whilst having the dose deposited in the lung from different formulations being the same.The three formulation developed are labeled Fluticasone Propionate Drug formulation 1 through 3.
Study Procedures and scheduling
The study is comprised of 5 visits in total - a screening visit and 4 treatment visits. At least 5 days should lapse between the treatment visits.
Screening Visit During the screening visit, the inclusion and exclusion criteria will be reviewed to ensure the volunteer is appropriate for the study. The informed consent will be reviewed with the volunteer by a member of the study team and the volunteer will be encouraged to ask questions to ensure the volunteer has a good understanding of the study. If the volunteer is eligible and agrees to participate, the volunteer will be asked to sign the informed consent form prior to any study specific procedures including randomization. After the volunteer signs the informed consent, the volunteer will be interviewed and demographic data, medical history and concomitant medications will be collected and recorded. A physical examination will be performed after the vital sign measurements are obtained. A pregnancy test for female volunteers will be obtained. Spirometry testing and inhalation training will be performed by a qualified study clinician/investigator to ensure the suitability of volunteers. Laboratory tests including a Complete Blood Count (CBC), urinalysis and metabolic panel will be collected via venipuncture and processed in the lab. Screening tests will be performed within 14 days of treatment visit 1 and no later than 2 days before treatment visit 1. All screening results will be evaluated by the study clinician/investigator against the inclusion/exclusion criteria to confirm the eligibility of the volunteers.
Inhalation training: Inhalation training will be performed by a qualified study clinician at the screening visit and at each study visit. The training will be accomplished by instructions and subsequent inhalation via training devices containing empty capsules. The instructions on how to use the device correctly are similar to the Foradil Aerolizer DPI product information label. (http://www.rxlist.com/foradil-drug/medication-guide.htm )
Treatment Visits 1, 2, 3 and 4 Eligible volunteers will be asked to return for treatment visit 1. A minimum period of 5 days should lapse between the subsequent treatment visits. Each treatment visit is scheduled for 28 hours over two days. The study will be conducted at the University of Florida (UF) CRC (Clinical Research Center). It is an outpatient study and the volunteer will be asked to come back the following day for the 24 hour blood sample. The volunteer will be asked to stay in an outpatient room during the treatment visit. The same activities are carried out at the other treatment visits.
At each treatment visit, eligibility criteria will be reviewed and confirmed to ensure volunteer is appropriate for study. Changes in medical history including concomitant medications will be documented. Vital signs will be obtained. Inhalation training will be provided to the volunteers as mentioned in the section above. An IV catheter will be inserted in a vein located in the forearm region of the volunteer. The IV catheter is used to avoid multiple pricks while collecting blood samples. The IV catheter is not used for the administration of the drug. The volunteer inhales 5 times from a given inhaler during each treatment visit. Each inhaler will be used only once and by only one volunteer to ensure the volunteer's safety from infectious agents. The schedule below summarizes the procedures performed at the screening visit and a single treatment visit.
Blood sample collection Blood samples will be drawn by inserting an indwelling catheter into the volunteer's median cubital vein in the forearm region. Blood samples will be taken 15 minutes prior to the dosing of the product (pre-dose sample) and 5, 10, 15, 20, 30, 45, 60 minutes, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours post dosing. At each time point 9ml of blood sample will be collected of which the first 1ml will be discarded and the remaining 8 ml will be stored in a vacutainer tube for plasma preparation and storage.
