Abstract:
The aim of the present investigation was to develop and evaluate physically improved
dry powder inhaler of peptide colistin sulfate (CS) using pulmosphere technology. CS
can improve the infectious condition if given in the form of pulmospheres as Dry
powder inhaler (DPI) dosage form. Fourier transform infrared spectroscopy (FTIR)
had employed to study drug-excipient incompatibility. Analytical method was
performed using UV spectrophotometer. DPI of CS pulmospheres was successfully
prepared with CS (22.8 mg), poly (lactide-co-glycolide) acid (PLGA) (227.2 mg),
sodium deoxycholate (1.5%w/v), mannitol (1%w/w) and magnesium stearate
(0.028%w/w) by solvent emulsification followed by spray drying method and
evaluated for particle size, percent drug entrapment, surface morphology, flow
property, aerosol performance, in-vitro drug release study, antimicrobial study and
stability study. Optimization of process parameter was done by Box behnken design
(BBD) using Design Expert software. Drug and excipients were found to be
compatible to each other which was confirmed by FTIR study. Optimization study of
process parameter shows that batch prepared with inlet temperature 65°C, aspiratory
rate 25 Nm3/hr, feed flow rate 1 ml/min considered as optimum condition for spray
drying. Particle size was found to be 3.67 ± 0.015 μm for optimized batch. Scanning
Electron Microscopy (SEM) study indicates that the particles were found to be in
spherical shape and porous in nature. Carr’s index, hausners ratio and angle of repose
were found to be 11.17 ± 0.67%, 1.13 ± 0.008 and 26.2 ± 0.155° respectively which
show good flow property of pulmospheres. Percent drug entrapment and in-vitro drug release were found to be 91.66 ± 0.4084% and 92.78 ± 0.44% respectively for
optimized batch. A fine particle fraction (FPF), fine particle dose (FPD), Mass median
aerodynamic diameter (MMAD) and Geometric standard deviation (GSD) were found
to be 66.98%, 66.04%, 2.54 μm and 1.67 respectively for optimized batch. CS shows
most promising antimicrobial activity and it is as effective as CS marketed
formulation. Stability study shows DPI containing CS pulmospheres was stable at
accelerated condition. The present study demonstrated that, a spray-dried powder is
suitable for respiratory deposition and hold great potential for treating diseases that
require direct lung delivery.
