Insitu gelling system : A Review
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paper_title: In situ-gelling gellan formulations as vehicles for oral drug delivery

paper_content:

Gels formed in situ following oral administration of 1% (w/v) aqueous solutions of gellan to rats and rabbits were evaluated as sustained-release vehicles. The formulation contained calcium ions in complexed form, the release of which in the acidic environment of the stomach caused gelation of the gellan gum. The in vitro release of theophylline from the rigid gellan gels followed root-time kinetics over a period of 6 h. Plasma levels of theophylline after oral administration of gellan solutions and a commercial oral sustained-release liquid dosage form containing an identical drug concentration were compared in both rats and rabbits. Bioavailability of theophylline from gellan gels formed by in situ gelation in the animal stomach was increased by four-fivefold in rats and threefold in rabbits compared with that from the commercial oral formulation. There was no significant difference in the mean residence times of theophylline when administered by these two vehicles.
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paper_title: A Floating Controlled-Release Drug Delivery System: In Vitro-in Vivo Evaluation

paper_content:

A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a density of 0.67 was prepared and compared in vitro and in vivo to Theo-dur. The in vitro release rate of the floating tablet was slower. In vivo scintigraphic studies for a floating and a heavy nonfloating tablet, under fasting and nonfasting conditions, showed that the presence of food significantly increased the gastric retention time for both tablets, and tablet density did not appear to make a difference in the gastric retention time. However, the positions of the floating and nonfloating tablets in the stomach were very different. Bioavailability studies in human volunteers under both fasting and nonfasting conditions showed results comparable to those with Theo-dur. The floating controlled-release theophylline tablet maintained constant theophylline levels of about 2 mg/mL for 24 hr, which may be attributable to the release from the agar gel matrix and the buoyancy of the tablet in the stomach.
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paper_title: In situ gelling pectin formulations for oral sustained delivery of paracetamol.

paper_content:

The purpose of this study was to evaluate the potential of a pectin formulation with in situ gelling properties for the oral sustained delivery of paracetamol (acetaminophen). The formulations consisted of dilute aqueous solutions (1% to 2% w/v) of low methoxy pectin containing calcium ions in complexed form, which on release in the acidic environment of the stomach caused gelation of the pectin. In vitro studies demonstrated diffusion-controlled release of paracetamol from the gels over a period of 6 h. A bioavailability of approximately 96% of that of a paracetamol solution could be achieved from gels containing an identical dose of drug formed in situ in the stomachs of rats, with appreciably lower peak plasma levels and a sustained release of drug over a period of at least 6 h.
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paper_title: Development of a Novel Controlled-Release System for Gastric Retention

paper_content:

Purpose. We report on the development of a novel controlled-release gastric retention system, which consists of a matrix tablet, coated with a permeable membrane. When immersed in simulated gastric fluid, the tablet expands. The tablet remains expanded for eighteen to twenty hours, during which time the drug is released. The tablet then either disintegrates into fragments or loses its integrity.
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paper_title: Thermally reversible xyloglucan gels as vehicles for oral drug delivery.

paper_content:

The potential, as sustained release vehicles, of gels formed in situ following the oral administration of dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed has been assessed by in vitro and in vivo studies. Aqueous solutions of xyloglucan that had been partially degraded by beta-galactosidase to eliminate 44% of galactose residues formed rigid gels at concentrations of 1.0 and 1.5% w/w at 37 degrees C. The in vitro release of indomethacin and diltiazem from the enzyme-degraded xyloglucan gels followed root-time kinetics over a period of 5 h at 37 degrees C at pH 6.8. Plasma concentrations of indomethacin and diltiazem, after oral administration to rats of chilled 1% w/w aqueous solutions of the enzyme-degraded xyloglucan containing dissolved drug, and a suspension of indomethacin of the same concentration were compared. Constant indomethacin plasma concentrations were noted from both formulations after 2 h and were maintained over a period of at least 7 h. Bioavailability of indomethacin from xyloglucan gels formed in situ was increased approximately threefold compared with that from the suspension. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for oral delivery of drugs.
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paper_title: Stimulus-Responsive “Smart” Hydrogels as Novel Drug Delivery Systems

paper_content:

ABSTRACTRecently, there has been a great deal of research activity in the development of stimulus-responsive polymeric hydrogels. These hydrogels are responsive to external or internal stimuli and the response can be observed through abrupt changes in the physical nature of the network. This property can be favorable in many drug delivery applications. The external stimuli can be temperature, pH, ionic strength, ultrasonic sound, electric current, etc. A majority of the literature related to the development of stimulus-responsive drug delivery systems deals with temperature-sensitive poly(N-isopropyl acrylamide)(pNIPAAm) and its various derivatives. However, acrylic-based pH-sensitive systems with weakly acidic/basic functional groups have also been widely studied. Quite recently, glucose-sensitive hydrogels that are responsive to glucose concentration have been developed to monitor the release of insulin. The present article provides a brief introduction and recent developments in the area of stimulus-re...
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paper_title: Modified PLA nano in situ gel: a potential ophthalmic drug delivery system.

paper_content:

A novel nano in situ gel forming system of 5-Fluorouracil (5-FU) was investigated for its potential use for conjunctival/corneal squamous cell carcinoma (CCSC). The study was conducted in two steps, in the first step PLA nanoparticles were prepared and characterized; in the second step the drug loaded PLA nanoparticles were dispersed in sodium alginate solution yielding the modified nano in situ system, which were evaluated in rabbit eye. Size and morphology of prepared PLA particles were verified by using dynamic light scattering (DLS), atomic force microscope (AFM) and scanning electron microscope (SEM). In vitro and in vivo study of free 5-FU, PLA nanoparticles and modified nano in situ system were conducted in simulated tear fluid and in rabbit eye respectively. PLA nanoparticles were in size range of 128-194 nm with spherical shape and smooth surface with narrow size distribution. No polymer drug interaction was found as confirmed by FTIR, NMR and DSC. XRD of PLA nanoparticles confirmed that 5-FU was present in the crystalline state. In vitro experiments indicated a diffusion controlled release of 5-FU from both PLA nanoparticles and modified nano in situ system with high burst effect. Modified nano in situ gel system (MNS) significantly increased the Cmax and AUC0-8 in aqueous humor as compared to 5-FU solution and PLA nanoparticles. Higher 5-FU level in aqueous humor was possibly because of increased retention time of gel matrix-embedded drug loaded nanoparticles. Overall results showed the potential of MNS for ophthalmic delivery in the therapy of CCSC.
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paper_title: A novel nasal delivery system of a Chinese traditional medicine, Radix Bupleuri, based on the concept of ion-activated in situ gel.

paper_content:

The purpose of this study was to develop a nasal in situ gel system for Radix Bupleuri employing gellan gum as a polymer. Radix Bupleuri in situ gel containing 0.2 mL essential oil extracted from 450 g Radix Bupleuri, proper solubilizing agents and gellan gum (0.5% w/v) was prepared and characterized. The antipyretic effect produced by in situ gel formulation was investigated in fevered rabbits and compared to an intranasal solution. The resulting in situ gel was a clear and light-yellow liquid, with viscosity of 346 mPa x s and caproic acid content of 1.31 +/- 0.01 mg/mL. Intranasal administration of this preparation to fevered rabbits decreased body temperature markedly (1.1 degree C at the doses of oil from 1.5 g Bupleuri/body) and the effect could last for 20-30 h. The results suggest that Radix Bupleuri in situ gel can be greater effective than the solution in the treatment of fever.
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Title: Insitu Gelling System: A Review

Section 1: Introduction
Description 1: Introduce the concept of insitu gel forming polymeric formulations and their role in drug delivery systems.

Section 2: Principle of Insitu Gel
Description 2: Describe the formulation and gelling mechanisms of insitu gel systems, including the types of gelling agents and triggers involved.

Section 3: Advantages of Insitu Gel
Description 3: Discuss the various benefits of using insitu gel systems in drug delivery, such as improved bioavailability, prolonged contact time, and reduced administration frequency.

Section 4: Suitable Drug Candidates for Insitu Gel Ideal Characteristics of Polymers
Description 4: List the ideal properties of polymers used in insitu gel systems and the types of drugs that are suitable for this delivery method.

Section 5: Polymers Used in Insitu Gelling System
Description 5: Describe different types of polymers, including natural and synthetic, that are utilized in insitu gelling systems.

Section 6: Different Approaches for Insitu Gel Drug Delivery
Description 6: Explain the various mechanisms and approaches employed for inducing insitu gelation in different drug delivery contexts.

Section 7: Applicability of Insitu Polymeric Drug Delivery System
Description 7: Highlight the different therapeutic areas and routes of administration where insitu gel systems are applied, such as ocular, nasal, rectal, and oral drug delivery.

Section 8: Clarity
Description 8: Detail the methods for assessing the clarity of formulated insitu gel solutions.

Section 9: Texture Analysis
Description 9: Discuss how to evaluate the texture, consistency, and gel strength of insitu gel formulations.

Section 10: pH of Gel
Description 10: Explain the process of determining the pH of insitu gel formulations and its importance.

Section 11: Sol-Gel Transition Temperature and Gelling Time
Description 11: Describe the measurements and significance of sol-gel transition temperature and gelling time in insitu gel systems.

Section 12: Gel-Strength
Description 12: Explain how to measure the gel strength of insitu gelling agents.

Section 13: Gelling Capacity
Description 13: Detail the visual assessment of gelling capacity using simulated tear fluid.

Section 14: Rheological Studies
Description 14: Describe the procedures for assessing the viscosity and rheological properties of insitu gel formulations.

Section 15: Isotonicity Evaluation
Description 15: Highlight the importance of isotonicity in ophthalmic formulations and its testing methods.

Section 16: Statistical Analysis
Description 16: Explain the statistical methods used to analyze data obtained from various tests on insitu gel formulations.

Section 17: High Performance Liquid Chromatography
Description 17: Introduce the use of HPLC in the analysis of insitu gel formulations.

Section 18: Fourier Transformer Infrared
Description 18: Describe the FTIR technique used to investigate potential drug-excipient interactions.

Section 19: Thermal Analysis
Description 19: Explain the methods of thermal analysis, such as TGA and DSC, used to study insitu gelling systems.

Section 20: In vitro Drug Release Studies
Description 20: Detail the procedures for conducting in vitro drug release studies using insitu gel formulations.

Section 21: Ocular Irritancy Studies
Description 21: Describe the process and importance of conducting ocular irritancy studies in rabbits.

Section 22: Sterility Testing
Description 22: Explain the sterility testing procedures as per the IP guidelines.

Section 23: Accelerated Stability Studies
Description 23: Describe the conditions and parameters monitored during accelerated stability studies of insitu gel formulations.

Section 24: Histopathological Studies
Description 24: Highlight the procedures and significance of histopathological studies in evaluating mucosal interaction with the insitu gel.

Section 25: Antimicrobial Activity
Description 25: Explain how antimicrobial efficacy studies are carried out for insitu gel systems.

Section 26: Recent Advancements
Description 26: Discuss recent advancements in insitu gel technology and novel drug delivery systems that utilize insitu gel formation.

Section 27: Conclusion
Description 27: Summarize the main points covered in the review, emphasizing the benefits and challenges of insitu gel systems in drug delivery.