OCULAR INSERTs of ofloxacin were prepared with objectives of reducing the frequency of administration, obtaining controlled release and greater therapeutic efficacy in the treatment of eye infections such as conjunctivitis, keratitis, corneal ulcers, etc. Polyvinyl alcohol (PVA) ofloxacin films were prepared by mercury substrate method. The OCULAR INSERTs were evaluated for drug-excipient interaction, physico-chemical characteristics, microbiological and in vitro and in vivo release studies. There was no interaction between drug and excipients as revealed by UV absorption and IR spectra of the pure drug, medicated and placebo formulations. The weight and thickness of the INSERTs were in the range of 57.3-126.0 mg and 55.6-99.3 microns, respectively for different formulations; casting of rate-controlling membrane increased the weight and thickness of the INSERTs. Tensile strength and percent elongation at break varied with the nature of rate-controlling membrane and film thickness. Moisture vapour transmission through films followed zero-order kinetics and decreased with increase in film thickness. The drug content varied from 99.53-99.86%. The method of exposure to UV radiation was used for sterilization of OCULAR INSERTs and no microbial growth was observed in any formulation during sterility testing by direct inoculation method. The influence of rate-controlling membrane of different polymers of ethyl cellulose (EC) and polymethacrylates (Eudragit RL100, Eudragit RS100) on release kinetics was studied. The drug release for prepared formulations with rate-controlling membrane of EC, Eudragit RS100 (ERS), Eudragit RL 100 (ERL) was found to be 85.80, 93.85 and 98.71%, respectively and followed zero-order kinetics. OCULAR INSERT F3 with rate-controlling membrane of Eudragit RS100, when INSERTed into the eye of rabbit showed controlled release up to 24 hours. There was a good correlation between in vitro and in vivo release data. The developed formulation was effective against selected microorganism during in vitro antimicrobial efficacy studies. PVA-ofloxacin OCULAR INSERTs with rate-controlling membrane of Eudragit RS100 are promising for controlled OCULAR delivery of ofloxacin.

Objective(s): OCULAR INSERTs are usually polymeric thin films with increased OCULAR residence time and sustained drug release capacity. Sodium alginate is a biocompatible and biodegradable carrier; however, initial burst release of encapsulated drug within it, is recognized as a challenge. Grafting – addition of functional moieties to a polymer– is a technique to modify polymers’ physicochemical properties, including higher ability to control drug release. Linezolid (LNZ) solution is used in consecutive doses in treatment of antibiotic-resistant Gram-positive bacterial infections especially induced by methicillin resistant Staphylococcus aureus (MRSA). Materials and Methods: Grafted alginate copolymers were synthesized using butyl methacrylate (BMC) and lauryl methacrylate (LMC) at two different reaction times (12 hr and 24 hr). Copolymerization was evaluated by 1H-NMR, Ft-IR, and TGA. Copolymer safety was examined by cytotoxicity test against HEK-293 cell. Linezolid INSERTs were prepared using optimized copolymers and characterized. Results: 1H-NMR, Ft-IR, and TGA confirmed the successful grafting of alginate copolymers. ALG-B24 and ALG-L12 showed the highest safety against HEK-293 cell line comparing with intact alginate. Linezolid INSERT characterization results indicated a slower linezolid release profile related to creation of a lipophilic structure. A better strength property for linezolid loaded ALG-B24 and ALG-L12 INSERTs was obtained while ALG-L12 showed a stronger adhesive force compared with intact alginate. Antibacterial efficacy on clinical isolated MRSA after 24 hr was similar to linezolid solution. Conclusion: Lipophilic alginate copolymer (ALG-L12) showed a sustained release capability while retaining its main feature in strong film forming ability so it seems to be a promising safe carrier.

Purpose: The poor bioavailability of drugs in the OCULAR delivery systems is an important issue and development of delivery systems with prolonged release profile could be in a major importance. This study aims to develop an OCULAR delivery system using electrospun nanofibers to be a candidate INSERT for delivery of triamcinolone acetonide. Methods: For this purpose, three different chitosan-based formulations were prepared by electrospinning method, and electrospun nanofibers were compared to a formulation comprising hydrophobic polymers (Eudragit S100 and Zein). The electrospun nanofibers were characterized by SEM and FTIR analyses. The release profile and release kinetic models of all the formulations were also examined. Results: The SEM photographs of electrospun nanofibers revealed that among the four designed formulations, formulation obtained by electrospinning of chitosan and PVP possessed the best quality and the minimum size (120 ± 30 nm), which resulted the most uniform and bead-free nanofibers. This formulation also possessed the prolonged release profile of triamcinolone acetonide and was the only electrospun nanofiber following the zero-order kinetic profile. Due to the small diameter and uniformity of this formulation, the prolonged and well controlled release profile, it could be taken into account as a candidate to overcome the drawbacks of the commonly used OCULAR delivery systems and be used as OCULAR INSERT. Conclusion: This study confirmed the ability of electrospun nanofibers to be used as OCULAR INSERTs for delivery of ophthalmic drugs.

Background and purpose of the study: Several polymeric systems have been used to fabricate OCULAR INSERTs for better OCULAR bioavailability and retention to drug of which gelling systems have shown advantages of convenient administration and increased contact time. The purpose of the present study was to develop a bioadhesive in-situe gelling OCULAR INSERT of Gatifloxacin using polymeric system of sodium alginate as gelling and chitosan as bioadhesive agent.Materials and methods: Polymeric OCULAR INSERTs of Gatifloxacin sesquehydrate (GS) were composed using sodium alginate and chitosan with glycerin as plasticizer by solvent casting method. The OCULAR INSERTs were investigated for physicochemical properties (thickness, weight variation, folding endurance and surface pH), mechanical strength (tensile strength, elongation at break), swelling index, and bioadhesion parameters. In vitro release studies were carried using a fabricated donor-receptor compartment model.Results: Cumulative drug released from the formulation ranged from 95-99% within 8-12h.The formulation D (2% sodium alginate and 1% chitosan) sustained the drug release for the longest period of time (12h). Zero-order release of the drug was from optimized formulation D. A high correlation coefficient (r=0.9845) was recorded between in vitro and in vivo drug release.Conclusion: Gatifloxacin sesquehydrate INSERTs have appreciable film forming properties and were found to posses good antimicrobial efficacy.

Background and purpose: A drug brochure or Patient Package INSERT (PPI) is a sheet of paper in drug package that provides necessary information for effective and afe use of drugs. PPIs are among the main sources of drug information for general public, so, they should be clear and comprehensible. The purpose of this study was to assess the attitudes of pharmacists about PPIs in Iranian drug packages. Materials and methods: In this cross-sectional study, 203 pharmacists working in pharmacies affiliated with Mazandaran University of Medical Sciences were selected via random sampling. The attitudes of pharmacists about drug brochures in Iranian drug packages were assessed using a researchermade questionnaire. Content validity of the scale was confirmed and its reliability was confirmed by calculating Cronbach's alpha in Excel 2013. Results: In this study, 76. 5% of pharmacists believed that physicians rarely ask about the contents of PPIs. Also, only 7% of pharmacists reported mistakes in PPIs to pharmaceutical technicians and experts. Findings showed that 69. 8% found that the information in Iranian PPIs do not have a considerable effect on enhancing their knowledge. Conclusion: According to this study, pharmacists believed that the PPIs were not helpful in terms of size and font of contents, enhancing pharmacists’,knowledge and caused more fear about drugs’,side effects. Therefore, appropriate measures should be taken by food and drug administration when preparing PPIs to improve the contents of PPIs.

Helical milling is an alternative hole-making machining process which presents several advantages when compared to conventional drilling. In the helical milling process, the tool proceeds a helical path while rotates around its own axis. Due to its flexible kinematics, low cutting forces, tool wear, and improved borehole quality may be achieved. In this study, a new helical milling process to create holes in hardened steel with a hardness of HRC 52 was used. Carbide INSERTs with PVD TiN coating were applied. Input parameters including cutting speed and feed rate were considered in 4 and 2 levels, respectively. In order to increase the reliability of the results, experiments were repeated 4 times and the total of 32 tests were performed. Other cutting parameters, such as axial and radial depth of cut were constant. Machining process was performed in dry state and without any lubricant. Output characteristics were tool wear, surface roughness, cutting force, machining time and material removal rate. Tool wear, surface roughness and forces, were measured by tool maker microscopy, roughness tester and dynamometer, respectively. The results showed that increasing the cutting speed on this type of hardened steel, decreases the surface roughness, machining forces and machining time. However, increasing the cutting speed and the feed rate enhances the tool wear and material removal rate considerably. Cutting speed and Feed rate of 50 m/min and 0. 05 mm/tooth, offered the best mechanical properties of the Machining.

DTH drilling is a reliable method for drilling in medium to hard geological structures. Considering the country's need for different types of drilling bits in various industries, with development of knowledge and production of them, it can limit the vast importation of these products. In this study, process of bit/rock collision taking into account interaction between the INSERT/body and stresses resulting from interference fit is simulated to determine proper tolerance for fitting, which is the most important factor limiting the life of drilling bit. Simulations were carried out taking account rotary motion of bit in addition to impact in single-INSERT condition with different angles of collision and also in a 3. 5 inch bit with 13 INSERTs. Mechanical properties of specimens made of DIN1. 6580 steel, used for manufacturing of bit body, were obtained through experiments. Then, in order to validate and also obtain appropriate mesh size, results of pin-hub interference fit simulations with selected parameters were compared to Lame's analytical method. Results show that interference tolerance and speed and angle of impact have great influence on stresses and process forces. In case of 1. 2% of interference, stresses in bit body are about to reach material strength. In the case of 0. 9% and 0. 6%, certain amount of plastic strain is also created in the body. The results of this study is greatly helpful in choosing fitting tolerance of INSERTs into bit body during manufacturing process.