Development and evaluation of terbutaline sulphate loaded-biodegradable microspheres for pulmonary delivery
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Date
2007
Authors
Mohammed Ahmed, Rehab Abdallah
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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 !Jm while that of PLGA were 0.76%, 31.17%,
84.52% and 8.64 !Jm 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 bi-exponential first order release kinetics models
respectively. The mean aerosols size (MMAD) of rehydrated PLA (2.53 1-1m) and
rehydrated PLGA (3.50 1-1m) generated using nebulizer were smaller than the
MMAD of PLA (11.10 1-1m) and PLGA (11.47 1-1m) 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
Keywords
Terbutaline sulphate , Loaded-biodegradable