Preparation, Characterization, and Evaluation of Cytotoxicity of Fast Dissolving Hydrogel Based Oral Thin Films Containing Pregabalin and Methylcobalamin.

The oral availability of many drugs is problematic due to the pH of the stomach, enzymes, and first-pass effects through the liver. However, especially geriatric, pediatric, bedridden, or mentally handicapped patients and those with dysphagia have difficulty swallowing or chewing solid dosage forms. Oral Thin Films (OTFs) are one of the new drug delivery systems that can solve these problems. Pregabalin (PG) and Methylcobalamin (MC), which are frequently preferred for pain originating in the central nervous system, were brought together for the first time using OTF technology in this study. In this study, a quantification method for PG and MC was developed and validated simultaneously. Optimum formulations were selected with organoleptic and morphological controls, moisture absorption capacity, swelling capacity, percent elongation, foldability, pH, weight variability, thickness, disintegration time, and transparency tests on OTFs prepared by the solvent pouring method. Content uniformity, dissolution rate, determination of release kinetics, SEM, XRD, FT-IR, DSC, long-term stability, and cytotoxicity studies on the tongue epithelial cell line (SCC-9) were performed on selected OTFs. As a result, OTFs containing PG-MC, which are non-toxic, highly flexible, transparent, compatible with intraoral pH, with fast disintegration time (<30 s), and acceptable in taste and appearance, have been developed successfully.

Synthesis of New Ester Derivatives of Salicylic Acid and Evaluation of Their COX Inhibitory Potential.

Salicylic acid is an NSAID with serious side effects on the GIS. The side effects of salicylic acid on the GIS are slightly reduced by acetylating salicylic acid. 12 new ester analogs of salicylic acid were synthesized with high yields in this study. The chemical structures of the synthesized compounds were characterized by 1 H-NMR, 13 C-NMR, and HRMS spectra. The inhibitory potential of the compounds was evaluated on COXs by in vitro and in silico studies. The COX2 inhibitory activity of the most potent inhibitor MEST1 (IC50 : 0.048 µM) was found to be much higher than the COX2 inhibitory activity of aspirin (IC50 : 2.60 µM). In docking studies, the strongest inhibitor among the compounds synthesized was predicted to be MEST1, with the lowest binding energy. Docking studies revealed that MEST1 extends from the hydrophobic channel to the top of the cyclooxygenase active site, forming various interactions with residues in the binding pocket.

Nanoemulsion-Based Hydrogels and Organogels Containing Propolis and Dexpanthenol: Preparation, Characterization, and Comparative Evaluation of Stability, Antimicrobial, and Cytotoxic Properties.

Recently, nanoemulsion-based gels have become very popular for dermal drug delivery, overcoming the disadvantages of conventional semi-solid drug forms. The aim of this study is to prepare and characterize nanoemulsion-based hydrogels and organogels containing combined propolis and dexpanthenol, and to compare their stability, antimicrobial, and cytotoxicity properties. Within the scope of characterization studies, organoleptic properties, drug content, morphology, pH, gel-sol conversion temperature, spreadability, viscosity, FT-IR, and release properties were evaluated in hydrogels and organogels. The characterization studies carried out were subjected to short-term stability evaluation at room temperature and refrigerator for 3 months. While no phase separation was observed in any of the formulations kept in the refrigerator, phase separation was observed in four formulations kept at room temperature. The release study successfully obtained an extended release for propolis and dexpanthenol. In the antimicrobial susceptibility study, Hydrogel 1 showed activity against S. aureus, while Organogel 1 showed activity against both S. aureus and S. epidermidis. In the cytotoxicity study against HDFa cells, both Hydrogel 1 and Organogel 1 were found to be nontoxic at low doses. These hydrogels and organogels, which contain propolis and dexpanthenol in combination for the first time, are promising systems that can be used in wound and burn models in the future.

Preparation and Characterization of Nanosuspensions of Triiodoaniline Derivative New Contrast Agent, and Investigation into Its Cytotoxicity and Contrast Properties.

Iodine-based contrast agents have limitations such as rapid clearance, potential renal toxicity, non-specific blood pool distribution, headache, and adverse events. Nowadays, it is quite common to work with nanosized systems in order to eliminate the side effects of contrast agents. This study aims to synthesize a new iodinated contrast agent, prepare its nanosuspension by using the nanoprecipitation method, investigate its cytotoxicity, and compare its contrast properties with iohexol and iopromide through in-vitro experiments. The values of nanosuspension particle size and zeta potential have been found to be ~ 400 nm and ~ (-) 15 mV, respectively. In-vitro cellular viability findings indicated that the nanosuspension has lower cytotoxicity than the iohexol and iopromide. In the computed tomography (CT) imaging study of contrast features of nanosuspensions and two commercial agents, which involved 86 CT examinations using 31 parameters and two different devices, it was found that iodine had a stronger presence in its nanosuspension form than in iohexol and iopromide, which were the other two commercial contrast agents, when used in equal amounts. Thus in the case of nanosuspensions contrast brightness was achieved by using less iodine, while the same brightness could be obtained with higher doses of iohexol and iopromide. CT imaging therefore be done without much chemical use, which indicates that it may witness fewer side effects in the future.

Investigation of boron nanosized particles prepared with various surfactants and chitosan in terms of physical stability and cell viability.

Nanosuspensions (NS) are one of the new generation drug carrier forms developed to overcome the deficiencies of drugs with poor water solubility or insolubility and are considered to be one of the most successful approaches to formulate compounds in recent years. Boron nitride (BN) is insoluble in water and chemically more stable than carbon, it offers better biological superiority although the application of carbon structures in the biomedical field has increased in recent years. Chitosan is a polymer with excellent processability and biocompatibility thanks to its high dielectric constant. In addition, chitosan has a high affinity for metal ions. This study aims to combine BN and chitosan, which have unique properties, using six different surfactants, and to investigate their long-term stability for the use of both in medicine. In this direction, 24 different BN NS formulations were prepared. The 6th and 12th months' stability of these formulations were studied at +25 °C, 60% relative humidity, and +4 °C. Also, the prepared formulations were evaluated by cell viability test and examined in terms of toxicity. FTIR spectra of the formulations were taken and their morphologies were characterized by SEM. Prepared NSs with Poloxamer 407 + Tween (N1 - N6) were found to be the most stable formulations for 6 and 12 months both at +4 °C and +25 °C. The fact that BN has a negative zeta potential and chitosan has a high positive zeta potential in formulations is very important in terms of their potential antimicrobial activities. The low cellular toxicity of BN NSs, especially chitosan-coated BN NSs, at higher concentrations shows that they have enormous potential in the diagnosis and treatment of diseases with boron-based compounds in the future.

Current Overview of Oral Thin Films.

The pharmaceutical industry is attempting to discover thin films as a new drug delivery system. Thin films have been described as an alternative approach to conventional dosage forms. They are a versatile platform that provides fast, local, or systemic effects. Additionally, these systems can be easily applied by themselves, especially for dysphagia patients, geriatric, pediatric, or bedridden patients, as well as patients who cannot easily access water. These drug delivery systems can be administered in various ways such as orally, buccally, sublingually, ocularly, and transdermally. This review examines oral thin films in all aspects from today's point of view and gives an idea about the growing market share in the world due to the increase in research fields and technological developments. At the same time, it provides an overview of the critical parameters associated with formulation design that affect of thin films, including the design of thin films, anatomical and physiological limitations, the selection of appropriate manufacturing processes, characterization techniques, and the physicochemical properties of polymers and drugs. It also provides insight into the latest thin-film products developed by various pharmaceutical companies.

Effects of Emulsion Formulations of Oleuropein Isolated from Ethanol Extract of Olive Leaf in Diabetic Rats.

This study was designed to investigate the effects of emulsion formulations of oleuropein isolated from ethanol extract of olive leaf in streptozotocin-diabetic rats. The rats were treated with the administration of the emulsion containing oleuropein at a low (150 mg/kg b.wt.) and high (225 mg/kg b.wt.) dose for 30 days. At the end of the study, blood samples were drawn from the heart of the rats to determine blood glucose, alanine transaminase, and aspartate transaminase levels. In addition, their liver tissues were dissected to determine the levels of glutathione and thiobarbituric acid-reactive substances, and superoxide dismutase activity. According to the results for both dose treatments, a statistically significant increase in superoxide dismutase activities and glutathione levels of the treated diabetic rats was observed when compared with those of the diabetic control rats. On the other hand, a statistically significant decrease in the levels of thiobarbituric acid-reactive substances, aspartate transaminase and alanine transaminase of the treated diabetic rats was determined. It should be highlighted that the administrations at the high dose were more effective compared to that of the low dose. Furthermore, a substantial decrease in the blood glucose levels of the diabetic rats exposed to the high dose was observed.

Nifedipine-loaded polymeric nanoparticles: Preparation and in vitro characterization.

The purpose of the current study was to prepare nifedipine (NF) loaded-PLGA nanoparticles (NPs) using two different methods (nanoprecipitation method (N-2) and emulsion-solvent evaporation method (N-4)) to achieve the sustained release of NF and to reduce its side effects, and also to investigate the in vitro characteristics of NPs (surface morphology, particle size and size distribution, encapsulation efficiency and in vitro release characteristics). SEM images of nanoparticles revealed their approximate spherical shape. The mean particle sizes of the prepared nanoparticles ranged from 294.27±7.93 to 424.92±4.96 nm with almost neutral zeta potential values (close to 0 mV). The percent encapsulation efficiency values of N-2 and N-4 formulations 13.03±1.82% and 18.96±1.95% (p=0.05), respectively. The extents of cumulative drug release from N-2 and N-4 in PB pH 7.4 medium were up to about 100 % in 38 days and 22 days, respectively (when comparing two formulations, p<0.05). PLGA nanoparticles are useful systems for the sustained release of NF, and hence for reducing its side-effects and increasing patient compliance.