Magnesium stearate increases salbutamol sulphate dispersion: what is the mechanism?
The objective was to understand the mechanism of enhancement in salbutamol sulphate (SS) respiratory deposition through addition of magnesium stearate (MgSt). The mixing of MgSt with micronized SS occurred using a Turbula mixer (101 rpm), whilst varying mixing time and MgSt concentration and size. Deposition of SS was determined by a twin-stage impinger. Particle size distributions were obtained using the Malvern Mastersizer 2000. Morphology was examined by scanning electron microscopy and surface energy determined using inverse gas chromatography. Mixing of SS with increasing concentrations of MgSt improved dispersion (FPF of 3.3% using 1% w/w MgSt, 4.5% using 5% w/w MgSt and 7.8% using 10% w/w MgSt compared with 1.4% of pure SS for 20mg doses) when mixed for 0.5h; SS dispersion improved further after 3.5h of mixing. In addition to the action of the MgSt in coating SS particles, a greater understanding of the function of MgSt particles in acting as micro-carriers and in changing the mixture structure through incorporation into agglomerates has been achieved. The mechanistic understanding of improvement in drug deposition using MgSt will allow more directed strategies to be employed in designing powder formulations for inhalation.
Tay
Tracy
T
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Das
Shyamal
S
Stewart
Peter
P
D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D004357:Drug Synergism; D013229:Stearic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*
D004337:Drug Carriers; D013229:Stearic Acids; C031183:stearic acid; D000420:Albuterol