In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations

Almeida, Hugo; Amaral, Maria Helena; Lobão, Paulo; Lobo, José Manuel Sousa

doi:10.1016/j.drudis.2013.10.001

Cited by 203 publications

(140 citation statements)

References 90 publications

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“…Conventional ophthalmic dosage forms, such as solutions and suspensions have many drawbacks, including -rapid precorneal elimination of the drug mainly due to nasolacrimal drainage (Abdelkader et al, 2011;Abdelkader et al, 2010), the need for frequent application, and pulse release from solutions in particular (Almeida et al, 2014). On the other hand, ophthalmic ointments, although provide a prolonged contact with the eye, they may trigger foreign body sensation, blurred vision and cause inconvenience to the patient Sintzel et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…Thrimawithana et al, 2012). These polymer-based systems are liquid at room temperature, but undergo sol-gel transition on the ocular surface hence prolonging ocular residence time (Almeida, et al, 2014). Stimuli that may trigger sol-gel phase transition of the polymer network on the ocular surface could be owing to physical (temperature, light) or chemical (ions, pH).…”

Section: Introductionmentioning

confidence: 99%

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Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies

Fathalla

Vangala

Longman

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

138

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, Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies, European Journal of Pharmaceutics and Biopharmaceutics (2017), doi: http://dx.doi.org/10. 1016/j.ejpb.2017.01.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThis study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using DSC and FT-IR. The gelation temperature (T sol-gel ), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. DSC and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used.P188 modified the T sol/gel of P407 bringing it close to eye temperature (35 o C) compared with the formulation containing P407 alone. Moreover, gels that comprised P407 and P188 exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations PP11 and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control KT release as only 48% of the KT released within 12 h. In addition, the HET-CAM and BCOP tests confirmed the nonirritancy of KT loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. MTT assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with KT showed reasonable and acceptable percent cell viability compared with control samples.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies

Fathalla

Vangala

Longman

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

138

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“…Its LD50 in laboratory mice is 16 g/kg body weight, which is close to sugar and salt (Karthikeyan et al, 2013). It has been reported that CS has wound healing properties, permeability enhancing characteristics as it enhances drug permeation through the cornea by opening the tight junctions between epithelial cells (Almeida et al, 2014). Furthermore, it has antimicrobial properties and is used in the production of wound healing dressings (Almeida et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

Fathalla

Khaled

Hussein

et al. 2015

Drug Development and Industrial Pharmacy

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The aim of this work was to formulate chitosan (CS) based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimised in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterisation studies using FT-IR and DSC. The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0 ± 2.4 nm to 257.2 ± 18.6 nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10 mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (P<0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS based NPs for the ocular delivery of KT.

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“…Previously synthetized ThioPASP (Mw 12-14 kDa, thiolated to an extent of 10% n/n) was characterized from ophthalmic biopharmaceutical aspects [16][17][18][19][20][21][22][23][24][25][26][27][28] . Polymer solutions were prepared with distilled water or phosphate buffer solution (pH 7.4) …”

Section: Methodsmentioning

confidence: 99%

“…We set out to prove that an in situ gelling mucoadhesive drug formulation, thiolated poly(aspartic acid) (ThioPASP), meets all of the important requirements of each of the aspects discussed above. Such formulations must spread on the corneal surface or in the cul-de-sac and provide a short gelation time, their pH must be $7.4, they must be isotonic and non-toxic and they must not cause visual interference (appropriate refractive index and transmittance) 26 . PASP has been proven to be biocompatible and biodegradable, thanks to its protein-like structure.…”

Section: Introductionmentioning

confidence: 99%

Mucoadhesive polymers in ophthalmic therapy

Horvát¹

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In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations

Cited by 203 publications

References 90 publications

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

Mucoadhesive polymers in ophthalmic therapy

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