Development and evaluation of Terbutaline Sulphate loaded-biodegradable microspheres for pulmonary delivery
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Date
2007
Authors
Rehab Abdallah, Mohammed Ahmed
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Abstract
Sustained-release terbutaline sulphate (TBS) microspheres were developed
using PLA R 203H and PLGA RG 504H polymers. The microspheres were
prepared using the double emulsion solvent evaporation method and the
amount of TBS entrapped in the microspheres was determined by UV
spectrometry. The influence of surfactants (PVA and sodium oleate) and gelatin
in the external phase and the pH in internal phase on the physical
characteristics of the microspheres were investigated. PVA (0.5 and 5%),
sodium oleate (0.1 and 0.5%) and pH (4, 5.8 and 7.4) were found to influence
the physical characteristics (size, yield, drug loading and entrapment efficiency)
of the microspheres. Conversely, gelatin (25, 50 and 100 mg) had no effect on
the physical characteristics of both PLA and PLGA microspheres. At optimum
level (PVA 0.5%, sodium oleate 0.1% and pH 7.4) the drug loading, entrapment
efficiency, yield and mean particles size of PLA were 0.85%, 34.99 %, 87.11%
and 6.55 μm while that of PLGA were 0.76%, 31.17%, 84.52% and 8.64 μm
respectively. The DSC thermal profiles revealed that the Tg of PLA and PLGA
microspheres shifted to a lower value when TBS incorporated into
microspheres. Moreover, the FTIR spectra also showed a shift in the
characteristic peak of TBS in microspheres. This indicates that molecular interaction had occurred between TBS and polymers within the microspheres.
The scanning electron microscope revealed that the surface structure of PLA
was more porous than that of PLGA microspheres. Furthermore, the release of
drug from PLA microspheres was faster than from PLGA microspheres. An
addition of gelatin to the formulation was found to prolong the release of drug
from the microspheres. Drug release at the initial rapid phase (6 h) from PLA
and PLGA without gelatin was 76.31% and 55.4% respectively while the
remaining amount was released within 24 h and 72 h respectively. In contrast,
drug release at the initial rapid phase from PLA and PLGA with gelatin was
35.4% and 22.4% respectively while the remaining amount was released within
144 h and >144 h respectively. The drug release from both PLA and PLGA
microspheres without gelatin fitted first order release kinetics model. However,
drug release from PLA and PLGA with gelatin followed the Higuchi and biexponential
first order release kinetics models respectively. The mean aerosols
size (MMAD) of rehydrated PLA (2.53 μm) and rehydrated PLGA (3.50 μm)
generated using nebulizer were smaller than the MMAD of PLA (11.10 μm) and
PLGA (11.47 μm) produced by a Rotahaler. In addition, the fine particle fraction
(FPF) of PLA (49.54%) and PLGA (37.50%) aerosolized by a nebulizer were
higher than the FPF of PLA (11.89%) and PLGA (10.57%) produced by a
Rotahaler. In conclusion, TBS- loaded PLA microspheres is a promising
candidate for pulmonary delivery of sustained-release TBS using a nebulizer.
Description
Master
Keywords
Pharmaceutical science , Terbutaline Sulphate , Pulmonary Delivery