Formulation and evaluation of rifampicin-loaded polymer!c particles for pulmonary delivery
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Date
2006-05
Authors
Masoud Abdulla Abdulla, Juma
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Abstract
Polymeric particles were developed using PLGA and mPEG-DSPE
biodegradable polymers. The influence of various formulation parameters on
physical characteristics of polymeric particles was investigated. The formulation
parameters investigated for PLGA were polymer type (RG 502, RG 503H and
RG 504), PVA concentration (2.5 and 5% w/v) and drug to polymer ratio (0.2:1,
0.5:1 and 1:1). The formulation parameters investigated for mPEG-DSPE were
polymer type (mPEG2ooo-DSPE and mPEGsooo-DSPE), drug to polymer ratio
(1:5, 1:10 and 1.5:10) and filter porosity (0.22 and 0.45 !Jm). The formulations
were prepared using a solvent evaporation method and the amount of rifampicin
encapsulated in polymeric particles was quantified using a UV
spectrophotometry. The mean particle size of mPEG-DSPE (241.5 nm) was
smaller than PLGA (3.7 !Jm). The PLGA microparticles yield {90.71 %) was not
affected by all factors. Among the PLGA studied, PLGA 503H had the highest
entrapment efficiency with 79.59% at a PVA concentration of 5 %w/v and drug
polymer ratio of 0.2: 1. The highest entrapment efficiency of mPEG-DSPE
nanoparticles was 100 % at a drug to polymer ratio of 1:5 and filter porosity 0.45
j.lm. Polymer type and filter porosity had no effect on entrapment efficiency,
yield and drug loading. However, drug to polymer ratio was negatively
correlated with the entrapment efficiency of nanoparticles. Thermal analysis
using DSC showed the T g of nanoparticles shifted to a lower value. However,
the FTIR spectra showed no shift in the characteristic peaks of drug and
polymer which indicated no chemical interaction between drug and polymer in
polymeric particles.
Drug release from PLGA microparticles was much slower than mPEG-DSPE
nanoparticles. The release was negatively correlated with PLGA type and
positively correlated with drug to polymer ratio. The burst effect was seen when
drug to polymer ratio reached 1: 1. Drug release from PLGA 503H microparticles
was the fastest (14.11 %in 12 hours) among PLGAs. The release from PLGA
504 fitted zero order kinetics whereas PLGA 502 and 503H followed
biexponential first order kinetics. Conversely, the release from mPEG-DSPE
followed the first order release kinetics and the fastest drug released form
nanoparticles (58%) occurred in 12 hours. The mPEG-DSPE type used had no
effect on the drug release profile from nanoparticles. However, increasing drug
to polymer ratio and filter porosity would prolong the release of drug from
nanoparticles.
The MMAD of mPEG-DSPE generated by nebulizer (2.6 f.Jm) and Rotahaler®
(5.8 !Jm) characterized by NGI was smaller than the MMAD of PLGA 503H
aerosols produced by nebulizer (6.9 f.Jm} and Rotahaler® (10.6 f.Jm}. In addition,
the FPF of mPEG-DSPE (== 40 %) was higher than the FPF of PLGA 503H (==15
%). Furthermore, 1% agar proportional method was used to test the
susceptibility of rifampicin against mycobacteriums. The MIC values of mPEGDSPE
for drug sensitive strain (H37Rv) (1 0 f.Jg/ml} and drug resistant strain
(JB74) (25 f.Jg/ml) were lower than raw rifampicin (35 and 200 f.Jg/ml
respectively). Therefore, it can be concluded that the mPEG-DSPE polymer is a
suitable carrier for pulmonary delivery of rifampicin.
Description
Keywords
Rifampicin-loaded polymeric particles , Pulmonary delivery