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. 2019 Apr 25:1:100014.
doi: 10.1016/j.ijpx.2019.100014. eCollection 2019 Dec.

Preparation and characterization of Alendronate depot microspheres based on novel poly(-ε-caprolactone)/Vitamin E TPGS copolymers

Christina Koulouktsi  1 , Stavroula Nanaki  1 , Panagiotis Barmpalexis  2 , Margaritis Kostoglou  3 , Dimitrios Bikiaris  1
Affiliations

Preparation and characterization of Alendronate depot microspheres based on novel poly(-ε-caprolactone)/Vitamin E TPGS copolymers

Christina Koulouktsi et al. Int J Pharm X. .

Erratum in

Abstract

In the present study, new aledronate (AL) loaded microspheres were prepared with the use of polycaprolactone (PCL)/Vitamin E d-ɑ-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) copolymers. Specifically, PCL-TPGS copolymers, prepared at several PCL to TPGS ratios (namely, 90/10, 80/20, 70/30 and 60/40 w/w) via a ring opening polymerization process, were characterized by intrinsic viscosity, proton nuclear magnetic resonance (1H NMR), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and enzymatic hydrolysis. Results showed that as TPGS content increases the intrinsic viscosity of the copolymer (and hence, the viscosity-average molecular weight) is decreasing, while FTIR analysis showed the formation of hydrogen bonds between the -C[bond, double bond]O of PCL and the -OH of TPGS. Additionally, XRD analysis indicated that the prepared copolymers were semi-crystalline in nature, while enzymatic hydrolysis studies showed that increasing TGPS content led to increasing copolymer hydrolysis. In the following step, AL drug-loaded microspheres were prepared via single emulsification process. Scanning electron microscopy (SEM) revealed the formation of coarse drug-loaded microspheres with particle size close to 5 μm, while XRD analysis showed that the API was amorphously dispersed only in the cases of high TPGS content. Furthermore, FTIR analysis showed that the API did not interact with the copolymer components, while in vitro drug release studies showed that increasing PCL content led to decreasing API release rate. Finally, analysis of the drug release profiles suggested that the API release mechanism was solely governed by the polymer matrix erosion.

Keywords: Aledronate; Controlled release; Long acting injectables; Microspheres; Polycaprolactone; Vitamin-E TPGS.

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Figures

None
Graphical abstract
Fig. 1
Fig. 1
Polymerization reaction for the preparation of the PCL-TPGS copolymers.
Fig. 2
Fig. 2
1H NMR spectra of neat PCL and PCL-TPGS copolymers.
Fig. 3
Fig. 3
FTIR spectra (a) and powder x-ray diffractograms (b) of neat PCL, neat TPGS and PCL-TPGS copolymers at several weight ratios.
Fig. 4
Fig. 4
DSC thermograms for neat PCL, neat TPGS and PCL-TPGS copolymers (a), and enzymatic hydrolysis results for neat PCL and PCL-TPGS copolymers (b).
Fig. 5
Fig. 5
SEM micrographs of neat (without API) and drug (AL) loaded polymeric PCL-TPGS microspheres.
Fig. 6
Fig. 6
FTIR spectra (a) and DSC thermograms (b) of AL drug-loaded microspheres.
Fig. 7
Fig. 7
XRD diffractograms of AL drug-loaded microspheres.
Fig. 8
Fig. 8
In vitro release profiles of AL drug-loaded microspheres.
Fig. 9
Fig. 9
Comparison between experimental (data points) and model release profiles (continuous lines).
Fig. 10
Fig. 10
Theoretical percentage drug released versus dimensionless time for several values of the dispersivity of the polymer particles size distribution.
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