Ocular Pharmacokinetics Profile of Different Indomethacin Topical Formulations

Bucolo, Claudio; Melilli, Barbara; Piazza, Cateno; Zurria, Monia; Drago, Filippo

doi:10.1089/jop.2011.0120

Cited by 25 publications

(11 citation statements)

References 22 publications

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“…Currently, these drugs are used topically for the inhibition of intraoperative miosis, management of postoperative inflammation, and other inflammatory conditions [11]–[13]. Although it is not at the clinical level, 0.5% indomethacin ophthalmic suspension containing hydroxypropylmethylcellulose (Indom, Alfa Intes Srl, Casoria, Italy) or 0.1% indomethacin ophthalmic solution with hydroxypropyl-β-cyclodextrin (Indocollirio, Bausch & Lomb IOM SpA, Vimodrone, Italy) attain high concentrations in ocular tissues in rabbits [14].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Efficacy of Topically Applied Nonsteroidal Anti-Inflammatory Drugs in Retinochoroidal Tissues in Rabbits

et al. 2014

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PurposeTo evaluate the pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs (NSAIDs) in the retinochoroidal tissues of rabbits.MethodsThe cyclooxygenase (COX) inhibitory activity of diclofenac, bromfenac, and amfenac, an active metabolite of nepafenac, were determined using human-derived COX-1 and COX-2. Each of the three NSAIDs was applied topically to rabbits, and after 0.5 to 8 hrs, the concentration of each drug in the aqueous humor and the retinochoroidal tissues was measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetics of the drugs in the tissues after repeated doses as is done on patients was calculated by a simulation software. The inhibitory effect of each NSAID on the breakdown of the blood-retinal barrier was assessed by the vitreous protein concentration on concanavalin A-induced retinochoroidal inflammation in rabbits.ResultsThe half-maximal inhibitory concentration (IC50) of diclofenac, bromfenac, and amfenac was 55.5, 5.56, and 15.3 nM for human COX-1, and 30.7, 7.45, and 20.4 nM for human COX-2, respectively. The three NSAIDs were detected in the aqueous humor and the retinochoroidal tissue at all-time points. Simulated pharmacokinetics showed that the levels of the three NSAIDs were continuously higher than the IC50 of COX-2, as an index of efficacy, in the aqueous humor, whereas only the bromfenac concentration was continuously higher than the IC50 at its trough level in the retinochoroidal tissues. The intravitreous concentration of proteins was significantly reduced in rabbits that received topical bromfenac (P = 0.026) but not the other two NSAIDs.ConclusionsTopical bromfenac can penetrate into the retinochoroidal tissues in high enough concentrations to inhibit COX-2 and exerts its inhibitory effect on the blood-retinal barrier breakdown in an experimental retinochoroidal inflammation in rabbits. Topical bromfenac may have a better therapeutic benefit than diclofenac and nepafenac for retinochoroidal inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Efficacy of Topically Applied Nonsteroidal Anti-Inflammatory Drugs in Retinochoroidal Tissues in Rabbits

et al. 2014

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“…The IN lipid formulations demonstrated higher drug loading and entrapment efficiencies at lower lipid contents compared to Castelli’s formulations. Bucolo et al [54] investigated the ocular pharmacokinetics of IN following a multiple dosing treatment regime (30 µL/eye; four times in 8 hrs) of 0.5% IN + hydroxypropylmethylcellulose, IN-HPMC and Indocollyre ® eye drops in conscious rabbits. The drug levels in the AH, RC and VH obtained 2 hrs post-topical administration of IN-HPMC and Indocollyre ® solution were 360 ± 40 and 100 ng/mL, 65 and 20 ng/g, and 7± 2 and 5 ± 2 ng/mL, respectively.…”

Section: Discussionmentioning

confidence: 99%

Topical ophthalmic lipid nanoparticle formulations (SLN, NLC) of indomethacin for delivery to the posterior segment ocular tissues

Balguri

Adelli

Majumdar

2016

European Journal of Pharmaceutics and Biopharmaceutics

157

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Purpose The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) and to investigate their potential use in topical ocular delivery. Methods IN SLNs (0.1% w/v) and NLCs (0.8% w/v) were prepared, characterized and evaluated. Their in vitro release and flux profiles across the cornea and sclera-choroid-RPE (trans-SCR) tissues and in vivo ocular tissue distribution were assessed. Furthermore, chitosan chloride (CS) (mol. wt. < 200 kDa), a cationic and water-soluble penetration enhancer, was used to modify the surface of the SLNs, and its effect was investigated through in vitro transmembrane penetration and in vivo distribution tissue studies. Results For the IN-SLNs, IN-CS-SLNs and IN-NLCs, the particle size was 226 ± 5, 265 ± 8, and 227 ± 11 nm, respectively; the zeta potential was −22 ± 0.8, 27 ± 1.2, and −12.2 ± 2.3 mV, respectively; the polydispersity index (PDI) was 0.17, 0.30, and 0.23, respectively; and the entrapment efficiency (EE) was 81 ± 0.9, 91.5 ± 3.2 and 99.8 ± 0.2%, respectively. The surface modification of the SLNs with CS increased the ocular penetration of IN. The NLCs maintained significantly higher IN concentrations in all ocular tissues tested compared to the other formulations evaluated in vivo. Conclusion The results suggest that lipid-based particulate systems can serve as viable vehicles for ocular delivery. The NLC formulations demonstrated increased drug loading capability, entrapment and delivery to anterior and posterior segment ocular tissues.

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“…Although cyclodextrins have been widely used for increasing the solubility of poorly water soluble drugs, the activity of this compound in ocular tissues is controversial. On the contrary, the bio adhesive nature of HPMC is highly beneficial in improving ocular drug bioavailability (63). …”

Section: Pharmacokinetics Of Various Ophthalmic Formulationsmentioning

confidence: 99%

A comprehensive insight on ocular pharmacokinetics

Agrahari

Mandal

Agrahari

et al. 2016

Drug Deliv. and Transl. Res.

342

249

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Eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment model of ocular drug delivery has been developed for describing the absorption, distribution and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems and routes of administration are discussed including factors affecting intraocular bioavailability. Factors such as pre-corneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, drug metabolism renders ocular delivery challenging and elaborated in this manuscript. Several compartment models are discussed those are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations.

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Ocular Pharmacokinetics Profile of Different Indomethacin Topical Formulations

Cited by 25 publications

References 22 publications

Pharmacokinetics and Efficacy of Topically Applied Nonsteroidal Anti-Inflammatory Drugs in Retinochoroidal Tissues in Rabbits

Pharmacokinetics and Efficacy of Topically Applied Nonsteroidal Anti-Inflammatory Drugs in Retinochoroidal Tissues in Rabbits

Topical ophthalmic lipid nanoparticle formulations (SLN, NLC) of indomethacin for delivery to the posterior segment ocular tissues

A comprehensive insight on ocular pharmacokinetics

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