Cyclodextrins in Nasal Delivery of Low-Molecular-Weight Heparins: In Vivo and in Vitro Studies

Yang, Tianzhi; Hussain, Alamdar; Paulson, Jennifer; Abbruscato, Thomas J.; Ahsan, Fakhrul

doi:10.1023/b:pham.0000032998.84488.7a

Cited by 67 publications

(43 citation statements)

References 21 publications

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“…Since risperidone was reported to include different cyclodextrin derivatives in aqueous solution (11), as solubilizing agents, DMβCD was utilized in nasal formulations to prepare a solution-type nasal gel of the drug. In addition, this material may also produce an absorption enhancing effect in nasal absorption of risperidone, since this effect appears to be most pronounced for DMβCD, as reported by Yang et al (12). Results of the formulation sieving experiment performed by our research group have confirmed that a stable solution-type nasal gel of risperidone could be obtained only when the DMβCD concentration in the nasal formulation was higher than or equal to 15 %.…”

Section: Formulation Of Risperidone Nasal Gelsupporting

confidence: 77%

Preparation and in vivo evaluation of a gel-based nasal delivery system for risperidone

Gao

et al. 2016

Acta Pharmaceutica

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The aim of this study was to prepare a nasal gel of risperidone and to investigate the pharmacokinetics and relative bioavailability of the drug in rats. Compared with oral dosing, the risperidone nasal gel exhibited very fast absorption and high bioavailability. Maximal plasma concentration (cmax) and the time to reach cmax (tmax) were 15.2 μg mL-1 and 5 min for the nasal gel, 3.6 μg mL-1 and 30 min for the oral drug suspension, respectively. Pharmacokinetic parameters such as tmax′, cmax and AUC of oral and nasal routes were significantly different (p < 0.01). Relative bioavailability of the drug nasal preparation to the oral suspension was up to 1600.0 %. Further, the in vitro effect of the risperidone nasal gel on nasal mucociliary movement was also investigated using a toad palate model. The risperidone nasal formulation showed mild ciliotoxicity, but the adverse effect was temporary and reversible.

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Section: Formulation Of Risperidone Nasal Gelsupporting

confidence: 77%

Preparation and in vivo evaluation of a gel-based nasal delivery system for risperidone

Gao

et al. 2016

Acta Pharmaceutica

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“…Previous studies in our laboratory suggest that an aerosolized aqueous solution of LMWH administered via the nasal and pulmonary routes does not produce therapeutic levels of antifactor Xa. (8) In a separate study, we showed that insulin administered as an inhalable dry powder is better absorbed compared to an aqueous solution of insulin. (9) Currently, it is not known if LMWH administered as a respirable dry powder in the presence or absence of inert carriers will produce therapeutic levels of antifactor Xa.…”

Section: Introductionmentioning

confidence: 94%

“…Compared to subcutaneous injection of LMWH, LMWH solutions administered via the pulmonary route produced a relative bioavailability of *32.5% (Table 1), which is much higher than that administered via the nasal route. (8) Interestingly, administration of the two powder formulations led to different pulmonary …”

Section: Pulmonary Absorption Studiesmentioning

confidence: 99%

“…In a series of articles, we have shown that it is feasible to administer LMWH via the oral, (5) nasal, (6) and pulmonary (7) routes and that the absorption of LMWH via the respiratory route can be increased in the presence of absorption promoters, including alkylmaltosides and cyclodextrins. (5)(6)(7)(8) However, there are concerns regarding the use of absorption promoters in drug formulations that are required to be administered via the respiratory route for long-term therapy. One of the safest formulation approaches is to prepare an aqueous solution or dry powder of the drug that can be inhaled as aerosolized droplets or particles.…”

Section: Introductionmentioning

confidence: 99%

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Inhalable Lactose-Based Dry Powder Formulations of Low Molecular Weight Heparin

Bai

Gupta

Ahsan

2010

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: Currently low molecular weight heparin (LMWH) is administered as subcutaneous injection. This study sought to investigate the feasibility of LMWH as an inhalable dry powder (DPI) formulation and evaluate the interaction of the drug with lactose when used as a carrier. The study also compares the extent of pulmonary absorption of LMWH administered as a dry powder with that administered as an aerosolized aqueous solution. Methods: The formulations were prepared by mixing LMWH in an aqueous solution of lactose followed by lyophilization of the resulting solution. The lyophilized preparation was then ground and sieved. Physical characterization of the formulations was performed by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), particle size analysis, and determination of aerodynamic diameter. For in vivo studies, formulations were administered to anesthetized rats, and drug absorption was monitored by measuring plasma antifactor Xa activity. Results and Conclusions: In the FTIR scan, all characteristic peaks of lactose and LMWH were observed, suggesting that there was no strong interaction between lactose and LMWH. Although the aerodynamic diameter of the formulation (DPI-2) that was sieved through 170-and 230-mesh screens was similar to that of the formulation (DPI-1) sieved through 120-and 170-mesh screens, the particle sizes of the two formulations were significantly different. Dry powder formulations of LMWH were better absorbed compared to an inhalable solution of LMWH. One of the dry powder formulations (DPI-2) produced an almost 1.5-fold increase in the relative bioavailability (41.6%) compared to the liquid formulation of LMWH (32.5%). Overall, the data presented here suggest that lactose does not adversely affect the physical-chemical characteristics of the drug, and that lactose can be used as a carrier for pulmonary delivery of LMWH.

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“…Arnold et al (2002) formulated nasal drops of a LMWH with tetradecylmaltoside (TDM), a non-ionic surfactant and a potent absorption enhancer. Yang et al (2004) exploited the effect of dimethyl-beta-cyclodextrin in LMWH-cyclodextrin formulations on tight junctions' permeability. Both groups reported enhanced nasal drug absorption mediated through opening of cell-cell tight junctions.…”

Section: Micro-delivery Platforms For Lmwhsmentioning

confidence: 99%

Low molecular weight heparins for current and future uses: approaches for micro- and nano-particulate delivery

et al. 2015

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Low molecular weight heparins (LMWHs), the anticoagulant drug of choice in many indications, had been suggested as novel drug treatment for a range of diseases. Their superior pharmacokinetic properties compared to unfractionated heparin (UFH), motivated scientists to explore new delivery systems for improved therapeutic outcomes. Micro-and nano-carriers, with the versatile nature and characteristics of materials used for their fabrication, are able to surmount the challenges opposed by their native structures. The present review discusses the recent perspectives on the development of micro-and nano-particulate vectors for the delivery of LMWHs through various routes. Special focus on the application of the suggested systems, their characterization and the achieved improved bioavailability will be given throughout the review.

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Cyclodextrins in Nasal Delivery of Low-Molecular-Weight Heparins: In Vivo and in Vitro Studies

Abstract: Of the cyclodextrins tested, DMbetaCD was the most efficacious in enhancing absorption of LMWHs both in vivo and in vitro. The study also suggests that cyclodextrins enhance nasal drug absorption by opening of cell-cell tight junctions.

Cited by 67 publications

References 21 publications

Preparation and in vivo evaluation of a gel-based nasal delivery system for risperidone

Preparation and in vivo evaluation of a gel-based nasal delivery system for risperidone

Inhalable Lactose-Based Dry Powder Formulations of Low Molecular Weight Heparin

Low molecular weight heparins for current and future uses: approaches for micro- and nano-particulate delivery

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