Lütfi Genç

Studies on controlled release dimenhydrinate from matrix tablet formulations

In this study, controlled release dosage forms of dimenhydrinate were prepared with different polymers as MC, HEC, Carbopol 934, Eudragit RLPM and Eudragit NE 30 D at different concentrations (2.5-10%). Direct compression (DC) and wet granulation (WG) techniques were used to prepare the tablets. Magnesium stearate was the lubricant while starch gel was the binder. For the quality control of tablets prepared according to 11 different formulations, weight deviation, hardness, friability, diameter-height ratio, content uniformity of the active substance and in vitro dissolution techniques were performed. Dissolution rate of these tablets was controlled by USP XXII dissolution method and the profile of each tablet was plotted and only for F 5 was evaluated kinetically.

Preparation and characterization of ascorbic acid loaded solid lipid nanoparticles and investigation of their apoptotic effects

In this paper, ascorbic acid (Vitamin C, AA) known as an antioxidant was successfully incorporated in solid lipid nanoparticles (SLNs) by hot homogenization and efficient delivery of AA to cancer cells. The obtained SLN formulations were characterized by Nano Zetasizer ZS and HPLC with the particle size being less than 250nm. AA-SLNs exhibited sustained release and high entrapment efficiency. According to MTT test results, AA-SLNs showed high cytotoxic activity compared to the free AA against H-Ras 5RP7 cells without damaging NIH/3T3 control cells. These results were supported by the Annexin V-PI and caspase-3 assay. Furthermore, as compared to the AA, AA-SLNs exhibited more efficient cellular uptake, accumulated in the cytoplasm and induced apoptosis which was observed by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Thus, the results of this study suggest that SLNs can be a potential nanocarrier system for AA.

Preparation and In Vitro Evaluation of Controlled Release Hydrophilic Matrix Tablets of Ketorolac Tromethamine Using Factorial Design

Controlled release matrix tablets of ketorolac tromethamine (KT) were prepared by direct compression technique using cellulose derivatives as hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), and carboxymethyl cellulose (CMC) in different concentrations (10–20%). The effect of polymer type and concentration was investigated on drug release by 2³ factorial design. For the quality control of matrix tablets, weight deviation, hardness, friability, diameter–height ratio, content uniformity of KT, and in vitro dissolution technique were performed. UV Spectrophotometric method was used to detection of KT in matrix tablets. This method was validated. Dissolution profiles of the formulations were plotted and evaluated kinetically. An increase in polymer content resulted with a slow release rate of drug as was expected. According to the dissolution results, tablets prepared with HPMC + HEC + CMC (F1 and F8) were found to be the most suitable formulation for KT. About 99.27% KT was released from F8 in 7 h.

Vitamin B12-loaded solid lipid nanoparticles as a drug carrier in cancer therapy

Abstract Nanostructure-mediated drug delivery, a key technology for the realization of nanomedicine, has the potential to improve drug bioavailability, ameliorate release deviation of drug molecules and enable precision drug targeting. Due to their multifunctional properties, solid lipid nanoparticles (SLNs) have received great attention of scientists to find a solution to cancer. Vitamin supplements may contribute to a reduction in the risk of cancer. Vitamin B12 has several characteristics that make it an attractive entity for cancer treatment and possible therapeutic applications. The aim of this study was to produce B12-loaded SLNs (B12-SLNs) and determine the cytotoxic effects of B12-SLNs on H-Ras 5RP7 and NIH/3T3 control cell line. Results obtained by MTT assay, transmission electron and confocal microscopy showed that B12-loaded SLNs are more effective than free vitamin B12 on cancer cells. In addition, characterization studies indicate that while the average diameter of the B12 was about 650 nm, B12-SLNs were about 200 nm and the drug release efficiency of vit. B12 by means of SLNs increased up to 3 h. These observations point to the fact that B12-SLNs could be used as carrier systems due to the therapeutic effects on cancer.

Microencapsulation of ketorolac tromethamine by means of a coacervation-phase separation technique induced by the addition of non-solvent

Ketorolac tromethamine (KT) is a non-steroidal drug with potent analgesic and anti-inflammatory activity and is absorbed rapidly (Tmax < 1.0 h) with an efficiency > 87% following oral and intramuscular administration. The plasma half-life of ketorolac ranges from 1.1 to 6.0 h. Its oral bioavailability is estimated to be 80%. Ketorolac has been found 36 times more potent than phenylbutazone, approximately twice as potent as indomethacin, and three times more potent than naproxen in suppressing carrageenan-induced paw oedema in rat. In this study, microcapsules of KT were prepared by means of coacervation-phase separation technique induced by the addition of non-solvent, and release rates from microcapsules were studied. Eudragit S100 was used as the coating material. Coacervation was achieved by the addition of cyclohexane at 2 ml/min at 25 degrees C and 1:4 solvent: non-solvent ratio was used. The microcapsules were washed with cyclohexane to harden the wall and dried at room temperature. Microcapsules with core:wall ratio of 1:1 and 1:2 were prepared and the particles obtained by sieving with an average diameter of 177-500 microns were used. The yield was calculated and the release properties of KT were investigated by USP XXII paddle method and using UV spectrophotometry at 318 and 323 nm.

Film-Coated Enteric Tablet Formulation of Ketorolac Tromethamine

AbstractA great majority of polymers used for pharmaceutical film-coating purposes have been derivatives of cellulose or methacrylate copolymers (Eudragit series) in most recent studies. The type and frequency of the ester substituents in the chemical structure of these polymers determines their water permeability and pH-solubility characteristics; therefore, different members of the series may be employed for taste-masking or as enteric-coating agents or dissolution rate-controlling membranes in sustained-release dosage forms. Ketorolac tromethamine (KT) is a non-steroidal drug with potent analgesic and anti-inflammatory activity and is absorbed rapidly (Tmax 87% following oral and intramuscular administration. The most frequent adverse effects occurring with KT are gastrointestinal disturbances such as peptic ulceration and gastrointestinal bleeding. For this reason, enteric-coated film tablets of KT were prepared in this study by the spray technique. Eudragit S-100 and...

Apoptotic effects of some carbazole derivatives on lung carcinoma and glioma cell lines

In this study, we aimed to study the apoptotic effects of 2-[(9-ethyl-9H-carbazol-3-yl)amino]-2-oxoethyl N,N-disubstituted dithiocarbamates on A549 lung carcinoma and C6 glioma cell lines. Cytotoxicity analyses of DNA synthesis and detection of apoptosis by flow cytometry were evaluated to determine the anticancer activity of the compounds on both cell lines. Compounds 2, 5, and 7 which exhibited significant cytotoxic activity in MTT assay were chosen for flow cytometric analyses to determine the apoptotic percent of cells. These compounds also exhibited better DNA synthesis inhibition activity on cancer cells. Finally, acetylcholinesterase inhibition potentials of the compounds were measured. Compound 7 carrying 4-(2-dimethylaminoethyl)piperazin-1-yl moiety was the most active apoptotic agent against A549 and C6 cells. Apoptotic effect of this compound can be attributed to its AchE inhibition activity. Compounds 2 and 5 also showed apoptotic effects on C6 glioma cell lines. Compounds 2, 5, and 7 can be identified as the most promising anticancer agents against A549 and C6 cancer cell lines.

Preparation and characterization of methotrexate-loaded microcapsules

Abstract Methotrexate (MTX) has toxic effect to healthy tissues. Microencapsulation coats particles with a functional coat to optimize storage stability and to modulate release. In the present study, a new MTX encapsulated microcapsules were synthesized for controlling MTX release. Controlled drug release provides releasing of efficient dose and prevent drug side effect to tissues and also protects MTX from oxygen, pH and other interactions. MTX was encapsulated through biocompatible hyaluronic acid (HA) and sodium alginate (SA) with an encapsulation system to reduce its toxicity and for controlled release. The microcapsules prepared by vibrating nozzle were cross-linked with SA, HA and calcium chloride. Nozzle diameter and MTX concentration were changed according to loaded MTX and encapsulation efficiency were determined using HPLC. For the reliability of the data, validation studies of the HPLC method were performed. The precision of the method was demonstrated using intra- and inter-day assay relative standard deviation (RSD) values which are less than 2% in all instances. For the characterization of microcapsules, particle size, drug loading and in vitro drug release studies were performed. Diameters of MTX-loaded microcapsules were acquired approximately 160, 400 and 800 µm. Surface morphology of encapsulated microcapsules were displayed with light microscope. Eighty-nine percent MTX encapsulation efficiencies were achieved. Encapsulated MTX microcapsules showed controlled release when compared to pure MTX. While powder MTX dissolved completely in 10 min in the dissolution medium, MTX release from encapsulated MTX microcapsules became 40 h in 0.1 M PBS pH 7.4, including NaCl. MTX release from MTX-loaded microcapsules was reached to 79%. Moreover, drug efficiency was examined in vitro cell culture tests. Viability of 5RP7 cells were decreased to 88.5% for 96 h. When MTX was given directly to 5RP7 cells, viability of 5RP7 cells was decreased to 49.7% for 96 h. Flow cytometry studies also showed that, MTX microcapsules induced apoptosis. The goal of this study is to provide controlled release of MTX and to reduce the toxic effect of MTX.

Characterization of Solid Lipid Nanoparticles Containing Caffeic Acid and Determination of its Effects on MCF-7 Cells

Many anticancer drugs that are currently used in cancer treatment are natural products or their analogues by structural modification. Caffeic acid (3, 4-dihydroxycinnamic acid; CA) is classified as hydroxycinnamic acid and has a variety of potential pharmacological effects, including antioxidant, immunomodulatory and anti-inflammatory activities. As a drug carrier, solid lipid nanoparticles (SLNs) introduced to improve stability, provide controlled drug release, avoid organic solvents and are obtained in small sizes. In this study, we developed solid lipid nanoparticles incorporating with caffeic acid using hot homogenization method. Caffeic acid loaded solid lipid nanoparticles were characterized regarding particle size, zeta potential, drug entrapment efficiency, drug release, scanning electron microscopy (SEM) and FT-IR. The effects of caffeic acid loaded solid lipid nanoparticles on MCF-7 cells were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dimethyl tetrazolium bromide (MTT) test and Annexin V-PI analysis. As a result, solid lipid nanoparticles could potentially be used for the delivery of caffeic acid and solid lipid nanoparticles formulation enhanced the effects of caffeic acid on MCF-7 cells. Some relevant patents are also referred in this article.

Preparation and characterization of nocodazole-loaded solid lipid nanoparticles

Abstract Nocodazole (NCD) has more carcinogenic effect than similar drugs. Moreover, it has low drug release time and high particle size. Solid Lipid Nanoparticles (SLNs) have been evaluated for decrease in particle size and therefore increase in drug release time, for such drugs. In this study, NCD has been successfully incorporated into SLNs systems and remained stable for a period of 90 days. NCD structure related to the chemical nature of solid lipid is a key factor to decide whether anticarcinogenic agent will be incorporated in the long term and for a controlled optimization of active ingredient incorporation and loading, intensive characterization of the physical state of the lipid particles were highly essential. Thus, NMR, FT-IR, DSC (for thermal behavior) analyses were performed and the results did not indicate any problem on stability. Moreover, SLNs were decreased size of NCD in addition to increase in time of the drug release. After SLN preparation, particle size, polydispersity index, electrical conductivity and zeta potential were measured and drug release from NCD-loaded SLNs were performed. These values seem to be of the desired range.