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Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
Preparation and Optimization of Pramipexole Hydrochloride Solid Dispersions to Improve Drug Release and
Yuanyuan Ding1,2, Zhenkun Su1, Guodong Liang1
1College of Pharmacy, Inner Mongolia Medical University, Hohhot, China.
Abstract:
Pramipexole dihydrochloride (PPX) is a Biopharmaceutical Classification System (BCS) Class I drug with a short half-life, and its aqueous solution is susceptible to photodegradation. To improve its dosing convenience, the aim of this study was to prepare sustained-release solid dispersion (SD) pellets via hot-melt extrusion (HME) using ethyl cellulose (EC) and polyethylene glycol 6000 (PEG6000). The preparation process was optimized using single-factor experiments and central composite design (CCD). Under optimal conditions (PPX:EC ratio 1:4, 12.5% PEG6000, preparation temperature 155°C), the PPX solid dispersion (PPX-SD) showed stable performance and sustained release characteristics. SEM, DSC, and PXRD confirmed the amorphous state of PPX, while FT-IR indicated protential hydrogen bonding interactions between PPX and the polymers. In vitro release studies showed slower and more controlled release under pH 6.8. In vivo studies in rats demonstrated that PPX-SD had a four-fold higher AUC0-∞ (41.37 ± 9.39 μg·h·mL-1) compared to the commercial formulation Sifrol® (9.52 ± 2.18 μg·h·mL-1, p < 0.05). Tissue distribution studies in rats revealed increased brain accumulation of PPX in the PPX-SD group. Thus, PPX-SD exhibited a sustained-release and markedly improved the bioavailability by maintaining supersaturated amorphous substances, inhibiting precipitation during the drug absorption phase. This formulation offers a robust scientific foundation for the treatment of Parkinson's disease.
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