Cyclodextrin solubilization of carbonic anhydrase inhibitor drugs: Formulation of dorzolamide eye drop microparticle suspension

Jansook, Phatsawee; Stefánsson, Einar; Þorsteinsdóttir, Margrét; Sigurdsson, Baldur B.; Kristjánsdóttir, Sigrún S.; Bas, Jon Fernández; Sigurđsson, Hákon Hrafn; Loftsson, Þorsteinn

doi:10.1016/j.ejpb.2010.07.005

Cited by 64 publications

(23 citation statements)

References 21 publications

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“…Acetazolamide HPbCD [72][73][74] Anandamides HPbCD [75,76] Cannabinoids (various) HPbCD [77] Ciclosporin aCD [78][79][80] Dehydroepiandrosterone HPbCD [81] Dexamethasone HPbCD, gCD [82][83][84][85][86][87][88] Diclofenac HPbCD, RMbCD [89] Dipivefrine SBEbCD [90] Disulfiram HPbCD [91,92] Dorzolamide RMbCD, gCD [88,93] Enalaprilat HPbCD [94] Enalapril maleate HPbCD [94] Ethoxyzolamide HPbCD [72] Fluorometholone HPgCD [95] Hydrocortisone HPbCD [96,97] Ketoconazole HPbCD [98] Loteprednol etabonate HPbCD, DMbCD [99] Pilocarpine aCD, bCD, HEbCD, HPbCD, SBEbCD [100][101][102][103] Prostaglandins HPbCD [104] Rufloxacin HPbCD [105] Thalidomide HPbCD [106] D 9 -Tetrahydrocannobinol aCD [107,108] Nasal drug delivery: Acyclovir HPbCD [115] 17b-Estradiol DMbCD [116] Insulin aCD, DNaCD, HPaCD, bCD, DMbCD, HPbCD [117] Midazolam SBEbCD [118,…”

Section: Drug Cyclodextrin Referencementioning

confidence: 99%

Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes

Loftsson

Brewster

2011

Journal of Pharmacy and Pharmacology

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232

114

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Objectives Cyclodextrins are useful solubilizing excipients that have gained currency in the formulator's armamentarium based on their ability to temporarily camouflage undesirable physicochemical properties. In this context cyclodextrins can increase oral bioavailability, stabilize compounds to chemical and enzymatic degradation and can affect permeability through biological membranes under certain circumstances. This latter property is examined herein as a function of the published literature as well as work completed in our laboratories. Key findings Cyclodextrins can increase the uptake of drugs through biological barriers if the limiting barrier component is the unstirred water layer (UWL) that exists between the membrane and bulk water. This means that cyclodextrins are most useful when they interact with lipophiles in systems where such an UWL is present and contributes significantly to the barrier properties of the membrane. Furthermore, these principles are used to direct the optimal formulation of drugs in cyclodextrins. A second related critical success factor in the formulation of cyclodextrin-based drug product is an understanding of the kinetics and thermodynamics of complexation and the need to optimize the cyclodextrin amount and drug-to-cyclodextrin ratios. Drug formulations, especially those targeting compartments associated with limited dissolution (i.e. the eye, subcutaneous space, etc.), should be carefully designed such that the thermodynamic activity of the drug in the formulation is optimal meaning that there is sufficient cyclodextrin to solubilize the drug but not more than that. Increasing the cyclodextrin concentration decreases the formulation 'push' and may reduce the bioavailability of the system. Conclusions A mechanism-based understanding of cyclodextrin complexation is essential for the appropriate formulation of contemporary drug candidates.

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Section: Drug Cyclodextrin Referencementioning

confidence: 99%

Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes

Loftsson

Brewster

2011

Journal of Pharmacy and Pharmacology

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232

114

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“…Besides that, it is well known that cyclodextrins do not have mucoadhesive properties; on the contrary, polymers such as sodium hyaluronate, carbopol, and hydroxypropylmethylcellulose are bioadhesive to the ocular surface and they are able to improve the ocular bioavailability of drugs. This latter fact has been well demonstrated in numerous studies 22,23 where ocular formulations with cyclodextrins were compared with or without the presence of bioadhesive polymers. These considerations fit with the data of the present study, where IND-HPMC and IND-CD formulations contain hydroxypropylmethylcellulose and hydroxypropyl-b-cyclodextrin, respectively.…”

mentioning

confidence: 81%

Ocular Pharmacokinetics Profile of Different Indomethacin Topical Formulations

Bucolo

Melilli²,

Piazza³

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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IND-HPMC treatment demonstrates a nonclinical ocular pharmacokinetic profile of indomethacin characterized by higher concentrations of drug in ocular tissues (4.7-, 4.3- and 3.7-fold higher in aqueous, vitreous, and retina, respectively) compared to the ND-CD-treated group. Taken together, these data seem to indicate that IND-HPMC formulation has good ocular distribution reaching relevant indomethacin levels in the back of the eye, and suggest that this formulation may be very useful for clinicians to manage retinal conditions.

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“…Dorzolamide/g-cyclodextrin complexes selfassemble together resulting in nano-or microparticles, which enhance and prolong drug delivery to the eye. 2 The rabbits were sacrificed after 34 days of drug administration by an intravenous injection of sodium pentobarbital. The eyes were enucleated and extra ocular tissues removed immediately after death.…”

Section: In Vivo Rabbit Modelmentioning

confidence: 99%

“…1 Recent in vitro and in vivo studies indicate that dorzolamide is applicable to the g-cyclodextrin nanoparticle drug delivery platform. 2 A pilot study in humans has also showed that dorzolamide nanoparticle g-cyclodextrin eye drops had a longer IOP lowering effect than Trusopt Ò and could possibly be administered once daily compared with 3 times a day for Trusopt. 3 Topically delivered carbonic anhydrase inhibitor dorzolamide is a widely used drug to treat glaucoma.…”

mentioning

confidence: 97%

Dorzolamide Cyclodextrin Nanoparticle Suspension Eye Drops and Trusopt in Rabbit

Jóhannesson

Moya‐Ortega

Ásgrimsdóttir

et al. 2014

Journal of Ocular Pharmacology and Therapeutics

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Cyclodextrin solubilization of carbonic anhydrase inhibitor drugs: Formulation of dorzolamide eye drop microparticle suspension

Cited by 64 publications

References 21 publications

Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes

Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes

Ocular Pharmacokinetics Profile of Different Indomethacin Topical Formulations

Dorzolamide Cyclodextrin Nanoparticle Suspension Eye Drops and Trusopt in Rabbit

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