FORMULATION AND EVALUATION OF BESIFLOXACIN NON-ERODIBLE OCULAR INSERTS

Objective: Ocular inserts offer many advantages over conventional dosage forms, like increased ocular residence, the possibility of releasing a drug at a slow and constant rate, accurate dosing, exclusion of preservatives, and increased shelf life. Besifloxacin is a very important drug for the treatment of infectious conjunctivitis. The present study was aimed to formulate and evaluate Besifloxacin Non-Erodible Ocular Insert using Pullulan and polyvinyl pyrrolidone as a drug reservoir, PEG 400 as a plasticizer, and Eudragit RS-100 as a rate-controlling membrane. Methods: Central composite design was employed to study the effect of independent variables, i.e., effects of Pullulan amount (X1) and PVP (X2) on the dependent variables, i.e., % moisture absorption and In vitro diffusion rate. After evaluation of all thirteen batches of ocular insert reservoir formulation, BSF2 and BSF4 were selected as a satisfactory formulation and was sandwiched between rate-controlling membrane, which was made up of Eudragit RS-100 (3 and 5%). Results: The drug content of all formulations was found to be in the range of 95.33 to 99.89 %. In vitro diffusion of Besifloxacin from reservoir formulations (BSF1 to BSF13) was found to be 62.44 to 70.62 %. In vitro diffusion rate of an ocular insert of Besifloxacin can offer benefits such as increasing residence time, prolonging drug release in the eye for 24 h. Eudragit RS-100, as a sustained drug release polymer, showed promising sustained released action. Conclusion: The study concluded that Besifloxacin non-erodible ocular inserts can be successfully developed using Pullulan and polyvinyl pyrrolidone, which will sustain the release of the drug also reduce the frequency of administration, and thereby may help to improve patient compliance.

Preparation of Gentamicin Sulfate Nanoparticles using Eudragit RS-100 and Evaluation of Their Physicochemical Properties

Improving permeability and absorption of drugs are critical research challenges in pharmaceutical science. Gentamicin sulfate is an aminoglycoside antibiotic, which is very active against gram-negative bacteria; however, it has very poor bioavailability. This study aimed to prepare gentamicin nanoparticles with the intention of increased bioavailability. Accordingly, Eudragit RS-100 nanoparticles loaded with gentamicin sulfate were prepared by the double emulsification and solvent evaporation method, a proper technique for encapsulating hydrophilic molecules. Nanoparticles’ suspensions with polymer to drug ratios of 1:1 ([Formula: see text] and 2:1 ([Formula: see text]) were prepared, lyophilized and evaluated for their production yield, physicochemical properties and morphology. The mean particle size was 195.67[Formula: see text]nm and 228[Formula: see text]nm for [Formula: see text] and [Formula: see text], respectively. The formulations’ loading efficiencies were relatively high (85.73 for [Formula: see text] and 85.20 for [Formula: see text]). The nanoparticles’ surface charge (+40.5[Formula: see text]mV) was sufficient to inhibit their aggregation and facilitate the nanoparticles’ absorption through the gastrointestinal tract. The results of differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) revealed that drug and polymer stabilized each other by physical interactions between their functional groups. Both formulations presented an initial burst drug release of nearly 20% after 30[Formula: see text]min in phosphate buffer (pH = 7.4). After 24[Formula: see text]h, [Formula: see text] did not release the drug completely, while [Formula: see text] released the whole drug. Overall, nanoparticles with proper characteristics were obtained. This study puts forward the necessity of conducting further research in order to explore the intestinal absorption of these nanoparticles and the possibility of being utilized for oral administration of gentamicin sulfate.

Formulation and Evaluation of Luliconazole Microsponges Loaded Gel for Topical Delivery

Microsponge containing Luliconazole (LCZ) with different proportion of drug:polymer (Ethyl cellulose and Eudragit RS 100) were obtained efficiently using Quasi-emulsion solvent diffusion method. Luliconazole is an anti-fungal drug used for the topical delivery. The purpose of the microsponge formulation is to control the release of LCZ drug to the skin through Microsponge Delivery System (MDS) known to be the novel technique which overcome the maximum concentration of active ingredient, frequency doses, and skin irritation. The prepared microsponges were examined using drug content, % production yield, % entrapment efficiency and in-vitro drug release. The formulation were subjected to in-vitro drug release studies for 6 hr in which it was concluded that Ethyl cellulose microsponges formulated by drug:polymer (1:1) and Eudragit RS 100 microsponges formulated by drug:polymer (1:3) showed maximum controlled release i.e., Increase in drug:polymer ratio (1:1 to 1:9) increased the production yield and entrapment efficiency of microsponges using Ethyl cellulose with no significant effect for Eudragit RS 100.Therefore, both formulation F1 and F2 was dispersed in carbopol gel preparation for controlled delivery of LCZ to the skin. Various physical parameters like pH, spreadability, viscosity and in-vitro drug diffusion studies were evaluated for the prepared gel formulations. Microsponge gel formulation i.e., FG1 showed better results for controlled release of 89.40% as compared to FG2 i.e., 92.18% over the period of 12 hrs which is performed in Franz Diffusion Cell. On basis of in-vitro diffusion studies for LCZ gel formulation, microsponges using Ethyl cellulose (FG1) was found to be best for its controlled release of LCZ for 12 hrs and followed zero order kinetics. Hence, formulated LCZ loaded gel have potential to treat fungal infections i.e., tinea pedis, tinea cruris and tinea corporis.

ELECTROSPINNING OF ST. JOHN'S WORT OIL LOADED MICROCAPSULES BASED PVA NANOFIBERS

In this study, it was achieved that the production of St. John's Wort oil loadad Eudragit RS 100/PVA microcapsules by emulsion/solvent evaporation method and the microcapsules were embedded in PVA nanofibers. Morphological analysis was carried out with SEM images of both microcapsules and nanofibers. The presence of St. John's Wort oil, PVA and Eudragit RS 100 polymers were confirmed in the chemical structure of microcapsules and nanofibers by FT-IR. According to experimental studies, microcapsules were produced to have a smooth surface, a spherical shape and a uniform particle size. The PVA concentration was kept constant at 10% wt and microcapsule concentrations were applied as 1, 3, 5, 7, and 9 wt %. Then, polymer solution properties were measured, such as conductivity, viscosity, and surface tension. It was determined that viscosity and surface tension values increased with microcapsule concentration increase, while conductivity did not change significantly. Nanofiber production was realized via the electrospinning method under the optimum process parameters. According to the SEM images and histogram, nanowebs have a fine fiber diameter, smooth surface, high quality and no bead structure. In addition, the average microcapsule size is 30 μm, average fiber diameter is 430 nm and the fiber diameter uniformity coefficient is 1,014. It is thought that this nanofiber surface containing microcapsules embedded in St. John's Wort has the potential to be used as a wound dressing.

PARACETAMOL DRUG LOADED MICROCAPSULE BASED NANOFIBER PRODUCTION

In this study, it was aimed to production and characterization of paracetamol (PCT) loaded microcapsules and microcapsule added electro spun PVA nanofibers. Eudragit RS 100 and PVA were used as the shell in the microcapsule structure, and PCT was used as the core material. First of all, the PCT loaded Eudragit RS 100/PVA microcapsules were produced by solvent evaporation method under the optimum process parameters. Then, properties such as conductivity, viscosity and surface tension of the microcapsule loaded PVA solution were measured and the effects of microcapsule concentration on the solution properties were determined. According to the solution results, while the viscosity increased with the microcapsule concentration, conductivity and surface tension did not change significantly except for the PVA-10 sample. After the electrospinning process, fibre morphology was determined by SEM and incorporation of microcapsules into the nanofibers was clearly demonstrated. It was calculated from the SEM images that average microcapsule size is 9.81μm, average fibre diameter is 550 nm and fibre diameter uniformity coefficient is 1.025. Finally, the incorporation of PCT loaded microcapsules into the nanofibers was chemically confirmed by FT-IR analysis. It is thought that the results of this study will be useful for controlled drug release, especially in medical textiles.

Liqui-Mass Technology as a Novel Tool to Produce Sustained Release Liqui-Tablet Made from Liqui-Pellets

The Liqui-Mass technology (also known as Liqui-Pellet technology) has shown promising results in terms of enhancing the drug release rate of water insoluble drugs in a simplistic approach. However, there is no current study on sustained-release formulation using the Liqui-Mass technology. In this study, an attempt was made to produce a sustained-release Liqui-Tablet for the first time using a matrix-based approach. The non-volatile co-solvent used in the investigation included Tween 80, Tween 20 and Kolliphor EL. The production of sustained-release propranolol hydrochloride Liqui-Tablet was successful, and data from the saturation solubility test and dissolution test did not show much difference among the mentioned non-volatile co-solvent. The best Liqui-Tablet formulation took 24 h for drug release to reach at around 100%. There seemed to be a synergistic retarding drug release effect when a non-volatile co-solvent and Eudragit RS PO were used together. The increase of Eudragit RS PO concentration increased the retardant effect. Kinetic drug release analysis suggests that the best formulation followed the Higuchi model. The flowability of pre-compressed Liqui-Tablet pellets had no issues and its size distribution was narrow. Liqui-Tablet was generally robust and most formulations passed the friability test. The study revealed that Liqui-Mass technology can be employed to sustain drug release.

Bioavailability Study of Propranolol Patch

Bioavailability is a measure of the rate and amount of drug or active ingredient that is absorbed by a drug product and available at the site of action. By definition, the bioavailability of a drug when administered intravenously is 100%. However, when a drug is given by a different route of administration, its overall bioavailability will decrease (since the drug is not completely absorbed and metabolized first pass effect) or may vary from patient to patient. Bioavailability is very important in pharmacokinetics. One of them is that bioavailability needs to be taken when calculating the doses for administering a drug other than by intravenous route. The aim of this study was to describe the bioavailability of propranolol in patch preparations. Propranolol is made in patch formulations using menthol, PEG, and various combinations of PVP and Eudragit. PVP and Eudragit each dissolved in alcohol and then mixed until homogeneous. Propranolol was dissolved with a menthol solution and then mixed into a solution of PVP and Eudragit. Finally, PEG is added to the solution and stirred until homogeneous and then poured into the patch mold. The patches produced were then measured for each patch and bioavailability assay. The patch formula produced can be used transdermally, but of the three formulas, the F3 formula with a ratio of PVP K30 and Eudragit RS-100 3: 7 gives the best results with a tmax of 2 hours, Cmax 79.33 µg / ml and AUC 49.07 µg hours / ml.