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.
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Rifampicin-loaded polymeric particles , Pulmonary delivery
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