Işık Özgüney

Transdermal Delivery of Diclofenac Sodium Through Rat Skin From Various Formulations

The aim of this study was to evaluate and compare the in vitro and in vivo transdermal potential of w/o microemulsion (M) and gel (G) bases for diclofenac sodium (DS). The effect of dimethyl sulfoxide (DMSO) as a penetration enhancer was also examined when it was added to the M formulation. To study the in vitro potential of these formulations, permeation studies were performed with Franz diffusion cells using excised dorsal rat skin. To investigate their in vivo performance, a carrageenan-induced rat paw edema model was used. The commercial formulation of DS (C) was used as a reference formulation. The results of the in vitro permeation studies and the paw edema tests were analyzed by repeated-measures analysis of variance. The in vitro permeation studies found that M was superior to G and C and that adding DMSO to M increased the permeation rate. The permeability coefficients (Kp) of DS from M and M+DMSO were higher (Kp=4.9×10−3±3.6×10−4 cm/h and 5.3×10−3±1.2×10−3 cm/h, respectively) than the Kp of DS from C (Kp=2.7×10−3±7.3×10−4 cm/h) and G (Kp=4.5×10−3±4.5×10−5 cm/h). In the paw edema test, M showed the best permeation and effectiveness, and M+DMSO had nearly the same effect as M. The in vitro and in vivo studies showed that M could be a new, alternative dosage form for effective therapy.

Comparison of Different Water/Oil Microemulsions Containing Diclofenac Sodium: Preparation, Characterization, Release Rate, and Skin Irritation Studies

The aim of the present study was to make a comparison of the in vitro release rate of diclofenac sodium (DS) from microemulsion (M) vehicles containing soybean oil, nonionic surfactants (Brij 58 and Span 80), and different alcohols (ethanol [E], isopropyl alcohol [I], and propanol [P]) as cosurfactant. The optimum surfactant:cosurfactant (S:CoS) weight ratios and microemulsion areas were detected by the aid of phase diagrams. Three microemulsion formulations were selected, and their physicochemical properties were examined for the pH, viscosity, and conductivity. According to the release rate of DS, M prepared with P showed the significantly highest flux value (0.059±0.018 mg/cm2/h) among all formulations (P<.05). The conductivity results showed that DS-loaded microemulsions have higher conductivity values (18.8–20.2 microsiemens/cm) than unloaded formulations (16.9–17.9 microsiemens/cm), and loading DS into the formulation had no negative effect on system stability. Moreover, viscosity measurements were examined as a function of shear rate, and Newtonian fluid characterization was observed for each microemulsion system. All formulations had appropriate observed pH values varying from 6.70 to 6.85 for topical application. A skin irritation study was performed with microemulsions on human volunteers, and no visible reaction was observed with any of the formulations. In conclusion, M prepared with P may be a more appropriate formulation than the other 2 formulations studied as drug carrier for topical application.

Preparation and characterization of naproxen-loaded electrospun thermoplastic polyurethane nanofibers as a drug delivery system

The design and production of drug-loaded nanofiber based materials produced by electrospinning is of interest for use in innovative drug delivery systems. In the present study, ultra-fine fiber mats of thermoplastic polyurethane (TPU) containing naproxen (NAP) were successfully prepared by electrospinning from 8 and 10% (w/w) TPU solutions. The amount of NAP in the solutions was 10 and 20% based on the weight of TPU. The collection period of the drug-loaded electrospun TPU fibers was 5, 10 and 20h, and they were characterized by FTIR, DSC and TGA analysis. The morphology of the NAP-loaded electrospun TPU fiber mats was smooth, and the average diameters of these fibers varied between 523.66 and 723.50nm. The release characteristics of these fiber mats were determined by the total immersion method in the phosphate buffer solution at 37°C. It was observed that the collection period in terms of the mat thickness played a major role in the release rate of NAP from the electrospun TPU mats.

Preparation of Arsenic Trioxide-Loaded Microemulsion and Its Enhanced Cytotoxicity on MCF-7 Breast Carcinoma Cell Line

In this study, an injectable microemulsion of arsenic trioxide (As2O3-M) was prepared for intratumoral injection and the suppressive effect of As2O3-loaded microemulsion on human breast cancer cells MCF-7 was compared with those of a solution of the drug. Microemulsion was made up of soybean oil as oil phase, a mixture of Brij 58 and Span 80 as surfactants, absolute ethanol as cosurfactant, and bidistilled water containing As2O3 solution as the aqueous phase. Microemulsion formulation contains 5 × 10−6 M As2O3. The pH of As2O3-M was adjusted to 7.35 ± 0.1 and the physicochemical stability of the formulation was observed. The particle size distribution and zeta potential of As2O3-M were measured by Zetasizer 3000 HSA. The mean droplet diameters of As2O3-M were determined as 8.6 ± 0.4 nm. As2O3-M exhibited 13.1 ± 0.9 mV zeta potential. The formulation was physically stable for 12 months at room temperature when kept in ampule forms, as well as after autoclaving at 110°C for 30 min. The antitumor effects of As2O3-M were examined on human breast cancer cells MCF-7. It was clearly demonstrated that As2O3-M had a significant cytotoxic effect on breast cancer cell lines, and the cytotoxic effect of As2O3-M was significantly more than that of regular As2O3 solutions. Even ∼ 3000 times diluted microemulsion formulation loaded with 5 × 10−6 M As2O3 showed a cytotoxic effect. As a result, this diluted concentration (∼1.6 × 10−9 M) was found 1000 times more effective than regular As2O3 solutions (5 × 10−6 M). According to the in vitro cytotoxicity studies, we concluded that when As2O3 was incorporated into the microemulsion (As2O3-M), which is a new drug carrier system, it suppresses tumor cell growth on multiple tumor lines. These results indicate that As2O3-M may exert a low cytotoxic effect on normal cells and may be effective as an antitumor agent that induces apoptosis.

The Absorption of 99mTc-alendronate Given by Rectal Route in Rabbits

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of osteoporosis. Absorption of ALD as oral formulation is very poor (0.5%–1%). Its bioavailability can decrease with food effect. It has some gastrointestinal adverse effects such as gastritis, gastric ulcer, and esophagitis. The aim of this study was to develop a rectal formulation of ALD as an alternative to oral route and to investigate the absorption of it by using gamma scintigraphy. For this reason, ALD was labeled with Technetium-99m (99mTc) by direct method. The radiochemical characterization of the 99mTc-ALD was carried out by paper chromatography, thin layer chromatography, and electrophoresis methods. The labeling efficiency of 99mTc-ALD was found 99% without significant changes until 6 h postlabeling at room temperature. The rectal suppositories containing 99mTc-ALD were prepared by fusion method using polyethylene glycol (PEG) 1500. The 99mTc-labeled ALD suppositories were administrated to rabbits by rectal route. Serial scintigrams over all bodies of the rabbits were obtained at different time intervals using a gamma camera. We found that the rectal absorption of 99mTc-ALD from suppository formulation was possible. According to our results, this formulation of ALD can be suggested for the therapy of osteoporosis as an alternative route.

The Preparation and Evaluation of Sustained Release Suppositories Containing Ketoprofen and Eudragit RL 100 by Using Factorial Design

The preparation of ketoprofen (KP) sustained release (SR) suppositories was designed according to the 32 × 21 factorial design as three different KP:Eudragit RL 100 ratios (1:0.5, 1:1, 1:2), three particle sizes of prepared granules (250–500, 500–710, and 710–1000 μm) and two different PEG 400:PEG 6000 ratios (40:60, 50:50). The conventional KP suppositories were also prepared by using Witepsol H 15, Massa Estarinum B, Cremao and the mixture of PEG 400:PEG 6000. The dissolution studies of suppositories prepared were carried out according to the USP XXIII basket method in the phosphate buffer (pH = 7.2) at 50 rpm, and it was shown that the dissolution time was sustained up to 8 hours. According to the results of the factorial design, the most important independent variable on t50 and t80 was drug:polymer ratios. The log of partition coefficient of KP was determined as 1.46, showing the high affinity to the oily phase. n exponent and kinetic studies were conducted to explain diffusion mechanism, and it is understood that if the inert KP:Eudragit RL 100 ratio is increased in the particles, the Fickian difusion dominates and the best kinetic turns to Higuchi from the Hixson-Crowell. There is neither crystalline form of KP nor degradation product in the suppositories detected with the differential scanning calorimetry (DSC) studies. In addition to these studies, antiinflammatory activity of SR suppositories also determined that it was significantly extended according to the conventional suppositories.

Properties of bioadhesive ketoprofen liquid suppositories: preparation, determination of gelation temperature, viscosity studies and evaluation of mechanical properties using texture analyzer by 4 × 4 factorial design

Abstract Context: Development and evaluation of thermosensitive and bioadhesive liquid suppositories containing ketoprofen (KP). Objective: This study was conducted to develope thermosensitive and bioadhesive liquid suppositories containing KP using poloxamer and different bioadhesive polymers and to investigate their gelation temperature, viscosity and mechanical properties. Materials and methods: Bioadhesive liquid suppositories were prepared by the cold method using poloxamer 407 (P 407), Poloxamer 188 (P 188) and various amounts of different bioadhesive polymers. Their gelation temperatures, viscosity values and mechanical properties were determined using texture analyzer by 4 × 4 factorial design. Results: It was seen that in presence of KP, gelation temperature of formulation P 407/P 188 (4/20%) significantly decreased from 64 to 37.1 °C. It is to be noted that addition of increasing concentrations of bioadhesive polymers lowered gelation temperature and its decrease was highest with addition of Carbopol 934 P (C). Results of texture profile analysis (TPA) showed that formulations containing C have significantly higher hardness and adhesiveness values than other bioadhesive formulations. According to TPA, gel structure of liquid suppository formulation F5, containing P 407/P 188/KP/C (4/20/2.5/0.8%), exhibited the greatest hardness, compressibilty, adhesiveness and besides greatest viscosity. Discussion and conclusion: According to mechanical properties and viscosity values, it was concluded that F5 could be a promising formulation.

Electrospun Thermoplastic Polyurethane Mats Containing Naproxen– Cyclodextrin Inclusion Complex

Abstract Incorporation of cyclodextrins (CDs) into electrospun nanofibrous materials can be considered as potential candidates for functional medical textile applications. Naproxen (NAP) is a type of non-steroidal anti-inflammatory drug commonly administered for the treatment of pain, inflammation and fever. Drug-inclusion complex formation with CDs is an approach to improve the aqueous solubility via molecular encapsulation of the drug within the cavity of the more soluble CD molecule. In this study, NAP or different NAP-CD inclusion complexes loaded nanofibres were successfully produced through electrospinning and characterised. The inclusion complex loaded mats exhibited significantly faster release profiles than NAP-loaded thermoplastic polyurethane (TPU) mats. Overall, NAP-inclusion complex loaded TPU electrospun nanofibres could be used as drug delivery systems for acute pain treatments since they possess a highly porous structure that can release the drug immediately.