Abstract:
The aim of the present investigation was to prepare and evaluate porous hyaluronic
acid based dry powder inhalation system of topotecan HCl using spray drying
technique. Topotecan Hydrochloride can improve the cancerous condition if given in
the form of porous hyaluronic acid microparticles as dry powder. Porous Hyaluronic
Acid based dry powder inhalation system of topotecan hydrochloride was evaluated
for particle size, percent drug entrapment, flow property, zeta potential, surface
morphology, aerosol performance, in-vitro drug release study and stability study.
Optimization of formulation parameter and process parameter were done by 32 full
factorial design and Box Behnken Design (BBD) using Design Expert software. FTIR
study shows that neither drug decomposition nor drug-excipients and excipientexcipient
interactions occurred in the formulation. Porous Hyaluronic Acid based dry
powder inhalation system of topotecan hydrochloride was successfully prepared using
Topotecan hydrochloride(0.5%w/w), Hyaluronic acid (1%w/w), Polystyrene latex
(4%w/w), Respitose SV001 (89.95%w/w), Magnesium stearate (0.028%w/w).
Optimization study of process parameter shows that batch prepared with inlet
temperature 100°C, aspiratory rate 50 Nm3/hr, feed flow rate 2 ml/min considered as
optimum condition for spray drying. Particle size, zeta potential, and percent drug
entrapment were found to be 2.41 μm, -57.5 mV and 84.57 ± 0.40%. Scanning
electron microscopy study indicates that the particles were found to be in spherical
shape with porous structure. Carr’s index, hausner’s ratio and angle of repose were found to be 13.71 ± 0.24%, 1.15 ± 0.01 and 27.98 ± 0.68° respectively which show
good flow property of porous dry powder. In-vitro drug release of optimized batch
was found to be 97.28 ± 1.01 % up to 24 hr. A fine particle fraction (FPF), fine
particle dose (FPD), Geometric standard deviation (GSD) and mass median
aerodynamic diameter (MMAD) were found to be 86.55%, 16.73 mg, 1.68 and 2.95
μm respectively for optimized batch. Stability study shows dry powder containing
topotecan hydrochloride porous dry powder was stable at accelerated condition. The
present study demonstrated that, a porous hyaluronic acid based dry powder
inhalation system is suitable for respiratory deposition and hold great potential for
deep lung targeting.
