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.

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 ...

Conventional eye drops show relatively low bioavailability due to poor precorneal contact time. In situ hydrogels are of great importance in providing sustained ocular drug delivery. By exhibiting elastic properties they resist ocular drainage of the drug leading to longer contact times. In the present study an in situ gelling thermoreversible mucoadhesive gel was formulated of an antibacterial agent, Moxifloxacin HCl using a combination of poloxamer 407 and poloxamer 188 with different mucoadhesive polymers such as Xanthan gum and Sodium alginate with a view to increase gel strength and bioadhesion force and thereby increased precorneal contact time and bioavailability of the drug. Formulations were evaluated for physical parameters like clarity, pH, spreadability, drug content, gelation temperature, gel strength, bioadhesion force and in vitro drug release study. Formulations were found transparent, uniform in consistency and had good spreadability within a pH range of 6.8 to 7.4. A satisfactory bioadhesion (3298 to 4130 Dyne/cm2) on the sheeps corneal surface and good gel strength (95 to 128 sec) was also observed. As the concentration of mucoadhesive polymers in the gel formulation increased, the rate of drug release decreased. The order of drug release was in order: Xanthan gum > Sodium alginate. It was concluded that a thermoreversible in situ gel of Moxifloxacin HCl can be formulated by combining with mucoadhesive polymers and used effectively as safe and sustained ocular drug delivery. This combination provided greater bioadhesion force and gel strength as compared to the thermoreversible polymers i.e., poloxamer 407 (PF 127) or 188 (PF 68) when used alone.

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Nifedipine is an antihypertensive BCS class II drug which has poor bioavailability when given orally. The objective of the present study was to increase the bioavailability of nifedipine, by formulation and evaluation of a buccoadhesive liquisolid system using magnesium aluminium silicate (Neusilin) as both carrier and coating material and dissolution media were selected based on the solubility studies. A mixture of carboxymethylcellulose sodium and carbomer was used as mucoadhesive polymers. Buccoadhesive tablets were prepared by direct compression. FTIR studies confirmed no interaction between drug and excipients. XRD studies indicated change/reduction in crystallinity of drug. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial specifications. The dissolution studies for liquisolid compacts and tablet formulations were carried out and it was found that nifedipine liquisolid tablets formulated from bioadhesive polymers containing 49% liquisolid system, 17.5% carbomer, and 7.5% carboxymethylcellulose sodium showed the best results in terms of dissolution properties. Prepared formulation batches were evaluated for swelling, bioadhesion strength, ex vivo residence time, and permeability studies. The optimized batch was showing promising features of the system. Formulating nifedipine as a buccoadhesive tablet allows reduction in dose and offers better control over the plasma levels.

However, because of mentioned limitations and difficulties related to them, the total number of products on the market is still limited. Although the concept of PEGylation to increase half-life of nanoparticles revolutionized the nanoparticle-mediated drug-delivery field, significant improvements are warranted in this area.

The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.