Preparation of levofloxacin loaded in situ gel for sustained ocular delivery: in vitro and ex vivo evaluations

Introduction: In the present research, erythromycin estolate loaded in-situ gel was formulated and evaluated for blepharitis in order to improve its therapeutic efficacy, precorneal residence time of the system and to enhance the ocular bioavailability. Material and Methods: The developed formulation was characterized by several parameters viz. FTIR, clarity, pH, gelation temperature, rheological studies, drug content, in vitro drug release studies, transcorneal permeation studies, bioadhesion studies, isotonicity and stability studies. Results: The optimized formulation exhibited non-fickian release diffusion with a sustained release of drug 82.76 ± 0.94% up to 8h and drug content 93.64%. Isotonicity revealed that the formulation was isotonic in nature and there was no shrinkage and busting of cells. Bioadhesion study was performed to check the adherence of the prepared in situ gel to the corneal surface for 4h. Ex vivo transcorneal permeation was observed to be significantly higher when compared with market eye drops. Histopathological studies were conducted to confirm the presence of normal ocular surface tissues by maintaining their morphological structures without causing damage to the tissues. The formulation was nonirritant as confirmed by the HET-CAM test. Stability studies and accelerated stability studies were conducted for 13 weeks and 26 weeks respectively and formulations were analyzed for the visual appearance, pH, viscosity, gelling capacity, drug content and in vitro drug release and results showed no change in the formulations. Conclusion: The formulation was therapeutically efficacious, sterile, stable and provided controlled release over a period of time. The developed system could be a viable alternative to conventional eye drops for treatment of various ocular diseases.

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Thermosensitive Brinzolamide in situ Gel Nanoemulsions, in vitro and ex vivo Evaluation

Biointerface Research in Applied Chemistry ◽

10.33263/briac111.77547764 ◽

2020 ◽

Vol 11 (1) ◽

pp. 7754-7764

Keyword(s):

Carbonic Anhydrase ◽

Ex Vivo ◽

Physical Stability ◽

Topical Administration ◽

Physicochemical Characteristics ◽

Spontaneous Emulsification ◽

In Situ Gel ◽

Physicochemical Features

Brinzolamide (BZ) is a carbonic anhydrase inhibitor with selectivity and affinity for the carbonic anhydrase type II isoenzyme that administrated topically as an ophthalmic suspension for reducing intraocular pressure. In this study, BZ in situ gel nanoemulsions (NEs) were developed and evaluated for transcorneal permeation via the bovine corneal membrane. The spontaneous emulsification method was employed to prepare BZ in situ gel NEs. Various physicochemical characteristics, including particle size, polydispersity index, pH, refractive index, and viscosity, were evaluated. Accelerated physical stability and in vitro drug release, as well as transcorneal permeation studies was performed by applying the Franz-type diffusion cells. Thermosensitive BZ in situ gel NEs with desired physicochemical features and sustained release profiles were designed in the current study. Optimized Formulations exhibited physical stability under different conditions. The transcorneal permeation of formulations was higher than that of suspension, especially for F3b formulation. According to the present in vitro and ex vivo evaluations, it is concluded that in situ gel NEs could be a topical administration of BZ as a suitable ocular drug delivery system.

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Formulation and Evaluation of Sustained Release Sumatriptan Mucoadhesive Intranasal in-Situ Gel

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol28iss2pp95-104 ◽

2019 ◽

Vol 28 (2) ◽

pp. 95-104

Author(s):

Hussein K. Alkufi ◽

Hanan J. Kassab

Keyword(s):

Drug Release ◽

Ex Vivo ◽

Poloxamer 407 ◽

Gelation Temperature ◽

In Vitro Drug Release ◽

In Situ Gel ◽

Ex Vivo Permeation ◽

Ex Vivo Permeation Study

Objective: The purpose of this study to develop and optimize nasal mucoadhesive in situ gel IG of sumatriptan ST (serotonin agonist) to enhance nasal residence time for migraine management. Method: Cold method was used to prepare ST nasal in-situ gel, using thermosensitive polymers (poloxamer 407 and/or poloxamer 188) with a mucoadhesive polymer (hyaluronic acid HA) which were examined for gelation temperature and gelation time, pH, drug content, gel strength, spreadability, mucoadhesive force determination, viscosity, in-vitro drug release, and the selected formula was subjected to ex-vivo permeation study and histological evaluation of the sheep mucosal tissue after application. Results: The results showed that the formula IG7 prepared from poloxamer 407(19%), poloxamer188 (4%) and HA (0.5%) had an optimum gelation temperature (32.66±1.52°C), gel strength (43.66± 1.52 sec), mucoadhesive force (8067.93± 746.45dyne\cm2), in-vitro drug release (95.98%) over 6hr, ex-vivo permeation study release (89.6%) during the 6 h. study with no histological or pathological change in the nasal sheep tissue. Conclusion: The ease of administration via a nasal drop of ST coupled with less frequent administration and prolong drug release, will enhance patient compliance.

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Formulation of nanoparticles loaded in situ gel for treatment of dry eye disease: In vitro, ex vivo and in vivo evidences

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2020.102112 ◽

2020 ◽

pp. 102112

Author(s):

Umesh D. Laddha ◽

Sanjay J. Kshirsagar

Keyword(s):

Dry Eye ◽

Ex Vivo ◽

Dry Eye Disease ◽

Eye Disease ◽

In Situ Gel

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A Novel Approach of Drug Localization through Development of Polymeric Micellar System Containing Azelastine HCl for Ocular Delivery

Pharmaceutical Nanotechnology ◽

10.2174/2211738507666190726162000 ◽

2019 ◽

Vol 7 (4) ◽

pp. 314-327

Author(s):

Sheetal Devi ◽

Vipin Saini ◽

Manish Kumar ◽

Shailendra Bhatt ◽

Sumeet Gupta ◽

...

Keyword(s):

Allergic Conjunctivitis ◽

Polymeric Micelles ◽

Ex Vivo ◽

Entrapment Efficiency ◽

Ph Sensitive ◽

Micellar System ◽

Ocular Delivery ◽

In Situ Gel ◽

Micelle Size

Background: Development of polymeric micelles for the management of allergic conjunctivitis to overcome the limitations of topical installation, such as poor patient compliance, poor stromal permeability, and significant adverse effects, increase precorneal residence time and efficacy, and also control the release of drug at the target site. Objective: The investigation was aimed at developing a polymeric micellar system of Azelastine HCl for Ocular Delivery. Methods: Drug loaded micelles of tri-block copolymers Pf 127 were prepared by Thin Film hydration method. The polymeric micelles formulations (F1 to F9) were assessed for entrapment efficiency, micelle size, in vitro permeation, ex vivo transcorneal permeation, in vivo Ocular Irritation, and Histology. Results: Optimized micelles formulation (F3), with the lowest micelle size of 92 nm, least polydispersity value of 0.135, highest entrapment efficiency of 95.30 ± 0.17%, and a cumulative drug permeation of 84.12 ± 1.26% in 8h, was selected to develop pH-sensitive micelles loaded carbopol in situ gel. The optimized in situ gel (G4) proved to be superior in its ex vivo transcorneal permeation when compared with Market Preparation and pure drug suspension, exhibiting 43.35 ± 1.48% Permeation with zero-order kinetics (r2 = 0.9944) across goat cornea. Transmission Electron microscopy revealed spherical polymeric micelles trapped in the gel matrix. A series of experiments showed hydration capability, non-irritancy, and histologically safe gel formulation that had appropriate handling characteristics. Conclusion: A controlled release pH-sensitive ocular formulation capable of carrying the drug to the anterior section of the eye via topical delivery was successfully developed for the treatment of allergic conjunctivitis.

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Formulation development and characterization of in-situ gel of Rizatriptan Benzoate for intranasal delivery

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i1-s.4685 ◽

2021 ◽

Vol 11 (1-s) ◽

pp. 1-6

Author(s):

Jalaram H Thakkar ◽

Shailesh T. Prajapati

Keyword(s):

Ex Vivo ◽

Gellan Gum ◽

Brain Targeting ◽

Great Promise ◽

Formulation Development ◽

In Situ Gel ◽

Rizatriptan Benzoate ◽

32 Factorial Design

The present investigation was aimed to formulate and characterize ion-activated in-situ gel loaded with Rizatriptan Benzoate (RIZ) for intranasal administration for brain targeting. The gel was further optimized for process and formulation parameters by using 32 factorial design. The optimized batch having the concentrations of gellan gum and HPMC E15 LV 33.83 mg and 9.6 mg respectively. Gel strength and mucoadhesive strength of the optimized formulation were found to be 32.54 sec and 2580.50 dynes/cm2 respectively. Moreover, improved in-vitro and ex-vivo release profile of in-situ gel were observed in comparison to drug solution. In a nutshell, the developed formulation holds a great promise in overcoming the limitation associated with currently marketed RIZ formulations and illustrates the potential use of ion-activated in-situ gel to administer the drug by nasal route for brain targeting. Keywords: In-situ gel, Rizatriptan benzoate, Ion-activated, Gellan gum, HPMC E15 LV, Brain delivery, Migraine

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Design and Evaluation of Natamycin Nanocrystals Loaded In Situ Gel for Ophthalmic Administration

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i38a32090 ◽

2021 ◽

pp. 307-324

Author(s):

Roshni Das ◽

Marina Koland ◽

S. M. Sindhoor

Keyword(s):

Particle Size ◽

Drug Release ◽

Zeta Potential ◽

Ex Vivo ◽

In Vitro Drug Release ◽

In Situ Gel ◽

Drug Content ◽

Ex Vivo Permeation

Background: Natamycin belongs to a large group of naturally occurring polyene antifungal antibiotics derived from Streptomyces natalensis. Natamycin has a restrictive pharmaceutical role because of its extremely low aqueous solubility, which severely reduces the bioavailability of the drug. To improve the absorption of the drug, nanocrystals of natamycin were prepared and incorporated into in situ gel. Aim: To improve the solubility and absorption of natamycin nanocrystals by preparing nanocrystal in situ gel of natamycin for ophthalmic delivery Methodology: Natamycin nanocrystal was prepared using Sono-Precipitation method. Box-Behnken approach was employed to assess the influence of independent variables, namely concentration of stabilizer, sonication time and amplitude on particle size and zeta potential of the prepared nanocrystal. Optimized natamycin nanocrystal in situ gel formulations was characterized for various parameters like pH, viscosity, drug content, in vitro drug release and ex vivo permeation studies. Results: The optimized formulation of natamycin nanocrystal with a particle size of 293.9nm and zeta potential -14.6mV was incorporated into in situ gels. The pH triggered in situ gel was prepared using Carbopol and Hydroxypropyl methylcellulose (HPMC)., which showed clear preparation, pH of the formulation was closed to the pH of tear fluid, i.e., 7.4, viscosity showed pseudoplastic behaviour with immediate gelation remained for an extended period, and the drug content was around 99.70%. From the characterizations given above, PF-4 was optimized and evaluated for In vitro drug release showing slow and sustained release when compared to the marketed formulation and followed first-order kinetics with the diffusion-controlled mechanism. Ex vivo permeation through goat's cornea of PF-4 showed better permeation than marketed formulation. The stability studies of PF-4 showed that formulation was stable at the appropriate condition. Conclusion: Nanocrystals formulations of natamycin was successfully formulated and incorporated into in situ gels. Further in vivo studies need to be carried out for confirmation of pharmacological activity

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