The real challenge in the development of a controlled drug delivery system is not just to sustain the drug release but also to prolong the presence of the dosage form in the stomach or the upper small intestine until all the drug is completely released in the desired period of time (1-2). The residence of a drug delivery system in the upper part of the gastrointestinal tract (GIT) can be accomplished by several drug delivery systems, such as intragastric floating systems (3), swelling and expandable systems (4), bioadhesive systems (5), modified shape systems (6), high density systems (7), delayed gastric emptying systems (8) and low density super porous systems (9).Domperidone is a synthetic benzimidazole compound that acts as a dopamine D2 receptor antagonist. Domperidone is also used as a prokinetic agent for treatment of up- The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing domperidone as a model drug. Box-Behnken design was employed in formulating the GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X 1 ), Carbopol 934P (X 2 ) and sodium alginate (X 3 ), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug (t 50 ) and diffusion exponent (n) were selected as dependent variables. Seventeen formulations were prepared, dissolution data obtained was fitted to the power law and floating profiles were analyzed. HPMC loading was found to be significant for floating properties. Carbopol loading had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of sodium alginate on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.

The present work describes the formulation development of ophthalmic in situ gelling system using thermo-reversible gelling polymer, i.e. Pluronic F 127 (PF127). Because of high concentration (20 to 25%w/v) of this polymer required for in situ gelation causes irritation to the eye. So, to reduce this concentration, an attempt was made to combine the PF127 with other polymers like hydroxy propyl methyl cellulose (HPMC) as a viscosity increasing agent or with polymers like carbopol 940, xanthan gum, and sodium alginate (high glucuronic acid content) showing a pH and cation-triggered sol-gel transition, respectively. Different batches were prepared of varying concentrations of these polymers with PF127 using cromolyn sodium 2%w/v in phosphate buffer pH 5.0. The formulations were optimized by the viscosity measurement and in vitro gelation study. Selected formulations were evaluated for in vitro drug release profile and indicated sustain drug release over a period of 10 h. Effect of sterilization on drug content, pH, clarity, and viscosity were also evaluated. Finally, we concluded that by using this type of combination system, we could reduce not only the concentration of individual polymers but also the side effects without compromising the in vitro gelling capacity as well as overall rheology of the system.

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Nowadays, in situ gel forming systems are of great importance, having the combined advantage being patient convenient with favorable residence time for enhancing ocular bioavailability and for reducing systemic side effects (1, 2). The sol-gel transition can be induced by a shift in the pH (Carbomer) (3), temperature (poloxamer) or by the presence of deacetylated gellan gum cations (Gelrite) (4).Poloxamer is a triblock copolymer made of polyethylene oxide (PEO) and polypropylene oxide (PPO) units. Formation of highly ordered structures such as cubic crystalline phase and intramolecular hydrogen bonds might promote gelation (6). The mucomimetic property of poloxamers is proposed to be due to their hydrophobic and hydrophilic sequences simulating mucin action by adsorption of the aqueous layer of tears on the hydrophobic epithelium. This makes them suitable for use as a drug delivery system. The purpose of the study was to develop an optimized thermoreversible in situ gelling ophthalmic drug delivery system based on Pluronic F 127, containing moxifloxacin hydrochloride as a model drug. A 3 2 full factorial design was employed with two polymers: Pluronic F 68 and Gelrite as independent variables used in combination with Pluronic F 127. Gelation temperature, gel strength, bioadhesion force, viscosity and in vitro drug release after 1 and 10 h were selected as dependent variables. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 33-36°C. Gelrite loading showed a positive effect on bioadhesion force and gel strength and was also found helpful in controling the release rate of the drug. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature, gel strength, bioadhesion force and drug release properties.Keywords: moxifloxacin, in situ gel, ophthalmic drug delivery, mucoadhesive polymers, 3 2 full factorial design * Correspondence; e-mail: divyeshshastri@gmail.com Unauthenticated Download Date | 5/8/18 7:32 AM Poloxamer 407 gives a colorless and transparent gel but requires higher concentration of about 25 to 30 % (m/V) to exhibit sol-gel phase transition at 37°C when used alone (7). Gelation temperature can be adjusted within the range of 33-36°C by modifying cross-linking agents (8), by mixing the different series of poloxamers (9), by changing the weight of poloxamers (10), or by changing the pH and ionic strength (11). However, studies have been focused on modulating only gelation temperatures of poloxamer solutions. There is lack of knowledge of the strength and bioadhesive force of gelled poloxamers.In the present study, an attempt was made to solve this problem by combining two poloxamers, i.e., Pluronic F 127 (PF 127) and Pluronic F 68 (PF 68), and developing a series of combinations with gelation temperature ranging from 30 to 36°C (12). They were found suitable for formulating an in situ gelling ophthalmic drug delivery ...

In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel. The formation of gels depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, electrical sensitivity, enzyme sensitive from which the drug gets released in a sustained and controlled manner. Routes of administration are oral, ocular, rectal, vaginal, injectable and intraperitoneal. Various biodegradable polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly (DL lactic acid), poly (DL-lactide-co-glycolide) and poly-caprolactone. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems and good patient compliance, good stability and biocompatibility characteristics make the in situ gel dosage forms very reliable. Evaluation of In situ gel systems include in vitro drug release studies, sol-gel transition temperature and gelling time, gel strength, viscosity & rheology, texture analysis, clarity. Commercial formulations of in situ polymeric systems are Regel Depot Technology, Cytoryn and Timoptic-Xe. Recent developments in the field of polymer science and technology has led to the development of various stimuli sensitive hydrogels like pH, temperature sensitive, which are used for the targeted delivery of proteins to colon, and chemotherapeutic agents to tumors. Sustained and prolonged release of the drug, good stability and biocompatibility characteristics make the in situ gel dosage forms very reliable. From a manufacturing point of view, the production of such devices is less complex and thus lowers the investment and manufacturing.