Optimization and Physicochemical Characterization of Thermosensitive Poloxamer Gel Containing Puerarin for Ophthalmic Use

Abstract

The eye is a very sensitive organ, which presents many challenges to develop effective ophthalmic dosage forms. Due to the lachrymation, the normal tear turnover and the drainage from the nasolacrymal duct, the ophthalmic solutions eliminate rapidly, which causes a short precorneal residence time and a limitation of transcorneal absorption. These lead to an ocular bioavailability that is commonly less than 10%. Meanwhile, after draining from the nasolacrymal duct into the gastrointestinal tract, some drugs may cause systemic side-effects.1-3) Although these drawbacks can be overcome in some degree by using several new preparations, such as ointments and inserts, these preparations present some disadvantages, such as blurred vision and noncompliance, which bring about some new problems to patients. 4)Compared to these preparations mentioned above, in situ gels have more advantages in these aspects. These systems consisting of polymers undergo sol-to-gel phase transitions as a result of a special physical/chemical change (for example, pH or temperature) induced by the physiological environment. 4,5) According to the different factors that cause solto-gel phase transitions on the eye surface, the ophthalmic in situ gels can be divided into the following three types: pH triggered (e.g. cellulose acetate hydrogen phthalate latex 6) and acrylic polymer 7) ), temperature-dependent (e.g. poloxamer 4,8) and Ethyl hydroxyl ethylcellulose 9)) and ion-activated (e.g. Gelrite ®10) and alginate 5)). Poloxamer is a block copolymer that consists of polyethylene oxide (PEO) units and polypropylene oxide (PPO) blocks and is known for exhibiting the phenomenon of reverse thermal gelation under a certain concentration and temperature. 4,[11][12][13] At a concentration of 18% (w/w) or higher in aqueous solution, poloxamer 407 (P407), in which the ratio of PEO and PPO is 7 : 3, is transformed from a low viscosity solution to a semisolid gel under the ambient temperature. 14)Depending on this character, it is possible to develop a new preparation that is a liquid form allowing a comfortable and precise delivery and shift to gel phase with a long precorneal residence time and high bioavailability after being triggered by the temperature of conjunctival sac (35°C). But the dilution by tear fluid is a factor that can't be disregarded, as the P407 solution of lower concentration will lose the gelation ability after diluted by tear fluid. 4) Considering this factor, 25.0% P407 (w/w) is essential to form gel in situ. In this case, the gelation temperature is lower than room temperature and the solution must be stored in refrigerator, which causes great inconvenience for the preparation and the use. Therefore, some regulatory substances were added to P407 solutions. El-Kamel attempted to reduce the poloxamer concentration without compromising the in situ gelling capacity by adding various viscosity enhancing agents such as methylcellulose, hydroxypropylmethylcellulose and sodium carboxymethylcellulose. 8) However, there was little informatio...

Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application

“…T gel decreased with further increment in PF--68 concentration. Similar results were previously reported (14). It is known that when the concentration and temperature of the polymer are above a critical value, pluronic molecules in aqueous solution will self-assemble to form spherical micelles with a dehydrated polypropylene oxide (PPO) core surrounded by hydrated swollen polyethylene oxide (PEO) chains (15).…”

“…The ratio of PEO/PPO in PF-127 is 7:3, while in PF-68 it is 8:2. Thus, when a slight amount of PF-68 is added to a PF-127 solution, the proportion of PEO increases, which leads to an increase in T gel (11,14). The possible reason for T gel decrease after a certain concentration of PF-68 (10 %) is that the incorporation of a small amount of PF-68 can only change the PEO/PPO ratio, causing an increase in T gel , while by increasing the PF-68 concentration sequentially, not only the PEO/PPO ratio changes, but also the micellization of PF-68 molecules can participate in the construction of the gel, which finally leads to a decrease in T gel (14).…”

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“…Therefore, small amounts of PL 68 added to PL 127 solutions can increase the proportion of PEO, which leads to a rise in gelation temperatures. [23] The drug-free polymer compositions were screened for visual appearance, clarity, gelation temperature, gel strength, syringeability, and injectability. Accordingly, six formulations were selected which showed satisfactory results after evaluation for the above parameters.…”

“…This increase as explained earlier is due to the thickening power of poloxamers in water and is related to the molecular weight and ethylene oxide/ propylene oxide ratio. [23][24][25] Formulations F4, F5, and F6 gelled at or close to 37°C, indicating that they would be successful in the conversion from sol-to-gel form after subcutaneous injection. This evaluation therefore consolidates the influence of the relative concentrations of PL 68 and PL 127 on the gelation temperature.…”

Doxorubicin-Loaded Zein <i>in Situ</i> Gel for Interstitial Chemotherapy

“…7) In situ gel has become increasingly attractive as a carrier for drug delivery systems because it is injectable, is biodegradable, has simple drug loading and is convenient for dose adjustment. [8][9][10][11][12] Polymers used for in situ gels [13][14][15][16][17] are mainly synthesized. In this study, Zein was used as the base material of an in situ gel for interstitial chemotherapy.…”