Enhancement of oral bioavailability of an HIV-attachment inhibitor by nanosizing and amorphous formulation approaches

Fakes, Michael G.; Vakkalagadda, Blisse; Qian, Feng; Desikan, Sridhar; Gandhi, Rajesh B.; Lai, Chiajen; Hsieh, Alice; Franchini, Miriam; Toale, Helen; Brown, Jonathan

doi:10.1016/j.ijpharm.2008.11.018

Cited by 97 publications

(57 citation statements)

References 20 publications

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“…The WAXD spectra of the PTx/POSS TPU blends with paclitaxel concentrations incremented by 20 wt % for all proportions were obtained and compared. As shown in Figure 2, 3 were also observed for all the other four POSS TPUs (see Supporting Information for WAXD results). In contrast, the crystalline paclitaxel as received shows several strong X-ray diffraction peaks at 2θ from 5°to 25°, which is consistent with the previous reports.…”

Section: Resultssupporting

confidence: 55%

“…As stated, this model assumes the ideal behavior of volume additivity and neglects potential influence of component interaction on K. Figure 4 shows that the T g -composition dependences of all PTx/POSS TPU blends were well fitted by the Gordon 3 for the other POSS TPUs), 10 eq 3 can be simplified as…”

Section: Resultsmentioning

confidence: 91%

“…Five POSS TPUs with varying PEG content were employed to form the blends with paclitaxel ( 3 employed the same initiator in the polyol segment but consisted of LA to CL repeat units of 90:10 in the feed mole ratio instead of pure LA.…”

Section: Resultsmentioning

confidence: 99%

“…The nature of the crystalline/amorphous morphology of the POSS TPUs, comparing with that of the POSS diol monomer, was examined using WAXD. The crystallization patterns of the POSS diol monomer and [P 1k LA 100 CL 0 ]-[LP] 3 have been previously described in some detail. 28,29 Similar to these prior results, as shown in Figure 1, the POSS diol monomer exhibits three strong characteristic diffraction peaks at scattering angles of 2θ = 7.9°, 10 (Figure 1) due to its lowest POSS crystallinity among the five polymers (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…The POSS TPUs were synthesized as described earlier. 10,28 A naming system of these polymers designed before 10 3 consisted of a P(DLLA-co-CL) soft segment prepared using an initiator of PEG M _ n =1 kg/mol instead of 1,4-butanediol, and molar feed ratio of LA to CL repeat units of 90:10.…”

Section: Methodsmentioning

confidence: 99%

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Blends of Paclitaxel with POSS-Based Biodegradable Polyurethanes: Morphology, Miscibility, and Specific Interactions

Guo

Knight

Wu³

et al. 2010

Macromolecules

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The morphology, miscibility, and specific interactions of paclitaxel (PTx) with a family of polyhedral oligosilsesquioxane (POSS)-based biodegradable thermoplastic polyurethanes (POSS TPUs) were investigated systematically using wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). These POSS TPUs incorporate an alternating multiblock structure formed by POSS hard segments and the soft segments composed of polylactide/caprolactone copolymer (P(DLLA-co-CL)). They feature variable poly(ethylene glycol) (PEG) content from 0 to 14 wt % through adjusting the poly(ethylene glycol) (PEG) molecular weight in P(DLLA-co-CL) soft segments of fixed molar mass of M _ n = 12 kg/mol and further to 52 wt % utilizing pure PEG M _ n = 1 kg/mol in the soft segments. Using WAXD, it was found that PTx is amorphous in all proportions in the PTx/POSS TPU blends prepared using a solutioncasting method. Interestingly, the PTx not only exhibits excellent miscibility in all of these PTx/POSS TPU blends over the whole range of the drug concentration, but also serves as an antiplasticizer by increasing the blend T g gradually from the polymer T g up to the T g of amorphous PTx. The T g -composition dependences in these blends were well fitted by the Gordon-Taylor equation. The glass transition breadth of the blends increases significantly only for drug concentrations higher than 50 wt % for most of the POSS TPUs, suggesting some spatial heterogeneity at these high drug concentrations. On the other hand, the slight increment of the blend melting temperature, T m , and latent heat, ΔH, indicates enhanced phase separation between the POSS hard segments and the TPU soft segments upon drug incorporation. Gordon-Taylor analysis and FTIR results confirm that the PEG incorporated in the POSS TPUs exhibits strong H-bonding interactions with the PTx. Although PEG can promote the favorable interactions in the PTx/POSS TPU blends, we showed that the more hydrophobic LA/CL repeat units are still required in the soft segments in order to achieve molecular-level miscibility. This systematic investigation of the PTx/POSS TPU systems may be of great value to design plasticizer/antiplasticizer for new polymer materials with controlled and tailored properties, especially for those PLA-or PCL-based biodegradable polymer systems.

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Section: Resultssupporting

confidence: 55%

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%