The influence of magnesium stearate and carrier surface on the deposition performance of carrier based dry powder inhaler formulations

Abstract

This study investigated the influence of the addition of Magnesium Stearate (MgSt) with commercial grade (Lactochem®) and smoothed carrier lactose particles (Nanolac®) on the performance of a budesonide-lactose dry powder inhaler (DPI) formulation. A Multi Stage Liquid Impinger (MSLI) was used to investigate the in vitro deposition profile of the budesonide-lactose formulations containing different concentrations of Magnesium Stearate (MgSt), a widely used lubricant in the manufacture of pharmaceutical solid dosage forms. Upon pre-blending Magnesium Stearate using high shear blending process the aerosolisation performance of the DPI generally increased. This study suggested that the addition of 0.25% w/w MgSt in the formulation with Lactochem (63-90 m sieved lactose) resulted in the greatest aerosolisation efficiency amongst the other Lactochem formulations, while for the Nanolac formulations the addition of 0.5% w/w MgSt resulted in the most efficient aerosolisation. This difference could be attributed to the different surface morphology between the two carriers used and therefore the difference in their interparticulate forces between the drug particles and the surface of the carrier. The study suggested that an optimum concentration of the MgSt needs to be reached in order to get balanced interparticulate forces between the drug particles and the carrier surface which will enable maximum aerosolisation deposition. The influence of storage humidity on the aerosolisation efficiency and therefore the adhesion properties of the same formulations were also investigated. The formulations were stored for 3 months at 25°C, 75%RH and 40°C, 75%RH. Storage humidity had a significant effect on the aerosolisation efficiency of all formulations except from the formulation containing 0.5% w/w MgSt. This could be due to the formation of a hydrophobic layer on the surface of the powder formulation, making it less sensitive to moisture. In addition, at high humidity, surface amorphous regions may have the ability to re-crystallize and effectively fuse to the lactose carrier surface, reducing the ability for the powder to be aerosolized and decreasing the FPF. This study suggests therefore, that an optimum concentration of the MgSt needs to be reached in order not only increase aerolisation efficiency but to maintain formulation stability upon exposure to elevated conditions of temperature and relative humidity. The use of a novel optical technology, the VariDose, was also investigated in order to obtain a system which can lead to an effective and efficient system for testing aerosol based systems for design, cycling, manufacturing and therapeutic management.

Date of Award	1 May 2008
Original language	English
Awarding Institution	University of Bath
Supervisor	Robert Price (Supervisor)