Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
Drug Dev Ind Pharm [journal]
- Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 21.:1-9.
Abstract Context: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action. Objective: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires. Materials and methods: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies. Results and discussion: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (Cmax) of 9140.84 ± 614.36 ng/ml at 3 h Tmax and solid dispersion tablets showed Cmax = 11 445.46 ± 149.23 ng/ml at 2 h Tmax. The area under the curve for the control and solid dispersion tablets was 31 495.16 ± 619.92 and 43 126.52 ± 688.89 ng h/ml and the mean resident time was 3.99 and 3.68 h, respectively. Conclusion: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug.
- Molecular interactions and solubilization of structurally related meso-porphyrin photosensitizers by amphiphilic block copolymers (Pluronics). [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 16.:1-10.
Abstract The influence of four Pluronics block copolymers (i.e. F68, P123, F127, and L44) on the aggregation and solubilization of five structurally related meso-tetraphenyl porphyrin photosensitizers (PS) as model compounds for use in Photodynamic Therapy of cancer (PDT) was evaluated. Interactions between the PSs and Pluronics were studied at micromolar concentration by means of UV-Vis absorption spectrometry and by kinematic viscosity (υ) and osmolarity measurements at millimolar concentrations. Pluronic micelles were characterized by size and zeta potential (ζ) measurements. The morphology of selected PS-Pluronic assemblies was studied by atomic force microscopy (AFM). While hydrophobic 5,10,15,20-Tetrakis(4-hydroxyphenyl) porphine (THPP) seemed to be solubilized in the Pluronic micellar cores, amphiphilic di(monoethanolammonium) meso-tetraphenyl porphine disulphonate (TPPS2a) was likely bound to the micellar palisade layer. Hydrophilic PSs like 5,10,15,20-Tetrakis (4-trimethylaniliniumphenyl) porphine (TAPP) seemed to form complexes with Pluronic unimers and to be distributed among the micellar coronas. TPPS2a aggregated into a network which could be broken at Pluronic concentration [Formula: see text] cmc, but would reconstitute in the presence of tonicity adjusting agents, e.g. sodium chloride (NaCl) or glucose.
- Effects of preparing techniques and aging on dissolution behavior of the solid dispersions of NF/Soluplus/Kollidon SR: identification and classification by a combined analysis by FT-IR spectroscopy and computational approaches. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 15.:1-13.
Abstract Context: Pharmaceutical solid dispersions are known to be seriously affected by issues of aging and processing. Objective: This study investigated the spectral patterns in the solid dispersions (SD) of Nifedipine/Soluplus/Kollidon SR and the feasibility of the methodology in identification and evaluation of the solid dispersions. Methods: The SD samples were prepared by hot melt extrusion (HMESD), solvent-evaporation (SESD), and fusion-cooling (FCSD). In order to distinguish the different SD samples, a combined analytical strategy by FT-IR spectrum, Raman spectrum, and computational approaches (PCA and HCA) were developed to investigate the spectral patterns of the solid dispersions. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and dissolution test were employed as the reference characterization. The stability test under the accelerated condition was carried out to investigate the physical stability of the SDs. Result: For the three prepared SDs, the evident differences on the dissolution behaviors and the trend of aging was observed. By means of the combined analytical strategy, the samples could be successfully identified in terms of their preparing techniques. The strength of hydrogen bonding interaction between NF and polymers decreased in the order of HMESD > SESD > FCSD. The results of the stability test indicated that the similarity factor f2 value of dissolution profile decreased in the order of HMESD > SESD > FCSD. HMESD exhibited a tendency of minimal changing on both dissolution behavior and spectral patterns. Conclusion: The combined strategy suggested the possibility for identification of specific SDs in quality control and prediction of their trends on the aging.
- A novel oleanolic acid-loaded PLGA-TPGS nanoparticle for liver cancer treatment. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 15.:1-11.
Abstract Objectives: Hepatocellular carcinoma is the third most common cause of cancer death. Oleanolic acid (OA) is a natural triterpenoid, has many important biological actions, including antitumor effect, but its poor solubility often leads to poor pharmacodynamics. The aim of our work is to make OA-loaded poly (lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (OPTN) to improve its efficacy to liver cancer and characterize it. Methods: OPTN were prepared by ultrasonic emulsification-solvent evaporation technique using PLGA with or without the addition of TPGS (OPN). The coumarin-6-loaded nanoparticles were used as a fluorescence marker. The nanoparticles were characterized for surface morphology, surface charge, particle size, drug loading, encapsulation efficiency, in vitro drug-release, cellular uptake, cytotoxicity by human liver cancer cell line HepG2 cells, and therapeutic effect in vivo. Key findings: The prepared nanoparticles were found to be spherical in shape. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake and cytotoxicity of OPTN in the HepG2 cells compared with that of OPN. The treatment of OPTN group was better than OPN and FS groups in vivo. Conclusion: The results showed advantages of OPTN in terms of sustainable release and efficacy in liver cancer chemotherapy compared with OPN. OPTN could be acted as a novel and new dosage form to be used in cancer treatment study.
- Co-delivery of paclitaxel and α-tocopherol succinate by novel chitosan-based polymeric micelles for improving micellar stability and efficacious combination therapy. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 14.:1-11.
Abstract The aim of this study was to develop chitosan derivative polymeric micelles for co-delivery of paclitaxel (PTX) and α-tocopherol succinate (α-TS) to the cancer cells to improve the therapeutic efficiency and reduce side effects of PTX. In this study, amphiphilic tocopheryl succinate-grafted chitosan oligosaccharide was synthesized and physically loaded by PTX and α-TS with entrapment efficiency of 67.9% and 73.2%, respectively. Physical incorporation of α-TS into the micelles increased the hydrophobic interaction between PTX and the micelles core, which improved micelle stability, reduced the micelle size and also sustained the PTX release from the micelles. The mean particle size and zeta potential of αTS/PTX-loaded micelles were about 133 nm and +25.2 mV, respectively, and PTX release was completed during 6-9 d from the micelles. Furthermore, the cytotoxicity of α-TS/PTX-loaded micelles against human ovarian cancer cell line cancer cell in vitro was higher than that of PTX-loaded micelles and the free drug solution. Half maximal inhibitory concentration values of PTX after 48-h exposure of the cells to the PTX-loaded micelles modified and unmodified with α-TS were 110 and 188 ng/ml, respectively.
- Elastic liposomes-in-vehicle formulations destined for skin therapy: the synergy between type of liposomes and vehicle. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 14.:1-7.
Abstract Objective: The present study is focused on optimization of elastic liposomes-in-vehicle formulations in respect to drug release and formulation properties. By combining penetration potential of elastic liposomes containing high ratio of entrapped drug and physicochemical properties of vehicles, both affecting the release and texture properties, optimal formulation could be achieved. Materials and methods: Deformable, propylene glycol-containing or conventional liposomes with hydrophilic model drug (diclofenac sodium) were incorporated into the following vehicles appropriate for skin application: a hydrogel, a cream base and derma membrane structure base cream (DMS base). Each formulation was assessed for in vitro drug release and mechanical properties. Results and discussion: The composition and type of both liposomes and the vehicle affected the rate and amount of the released drug. The cream base exhibited the slowest release, followed by the hydrogel and DMS base. Similar release profiles were achieved with both types of elastic vesicles (deformable and propylene glycol liposomes); the slowest release was observed for conventional liposomes, regardless of the vehicle used. The drug release profiles from different liposomes-in-vehicle formulations were in agreement with the physicochemical properties of the formulations. All of the liposomes were found to be compatible with the hydrogel preserving its original textures, whereas a significant decrease in all texture parameters was observed for liposomes-in-DMS base, regardless of liposome type. Conclusion: Propylene glycol liposomes-in-hydrogel is considered as the optimal formulation for improving skin delivery of hydrophilic drug. Further investigations involving in vivo animal studies are necessary to confirm its applicability in skin therapy.
- Solid self microemulsification of Atorvastatin using hydrophilic carriers: a design. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 14.:1-10.
Abstract Context: Atorvastatin has a limited advantage to formulate oral dosage forms. Objective: To enhance the solubility of Atorvastatin and to design the suitable solid self-microemulsifying drug delivery systems (S-SMEDDS) Materials and methods: The clear and transparent self-microemulsifying drug delivery system (SMEDDS) were formulated using coconut oil and isopropyl myristate as lipid phases; Tween 80 as surfactant; PEG 400 and glycerin as co-surfactant at 2:1, 3:1, 1:2 and 1:3 ratio. The pseudo ternary phase diagrams were constructed to identify the microemulsion region. The SMEDDS were evaluated for zeta potential, poly dispersity index, globule size, pH, viscosity and drug release. The solid SMEDDS were developed by employing adsorption and melt granulation methods. The S-SMEDDS were evaluated for micromeritics, morphology, solid state property, reconstitution ability, drug release and stability. Results: The micro formulations formed with particle size of 25 nm had shown a 3-folds rise in drug release. The solid SMEDDS had reconstituted to a good microemulsion rapidly in 1-3 min, with a release of 94.62% at the end of 30 min and behaved as immediate releasing capsules. Their shelf-life was found to be 1.3 years. Discussion: The 1:3 ratio SMEDDS had shown more drug release owing to their less particle size. The solid SMEDDS had shown an increased dissolution profiles than atorvastatin. The solid state of the drug had changed in formulation inferring their enhanced solubility. Conclusion: The solid form of atorvastatin liquid SMEDDS had been formulated successfully with enhanced shelf life and solubility.
- Comparison of cytotoxicity in vitro and irritation in vivo for aqueous and oily solutions of surfactants. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 14.:1-5.
Abstract The in vivo model on rabbit eyes and the in vitro cytotoxicity on fibroblasts were used to compare irritation effect of aqueous and oily (Miglyol 812) solutions of surfactants. Tween 20, Tween 80 and Cremophor EL were tested in different concentrations (0.1, 1 or 5%) and the in vitro test demonstrated that surfactants in oil are less cytotoxic than in aqueous solutions. In the in vivo study, the aqueous solutions of surfactants were characterized as non-irritant while small changes in conjunctiva were observed after application the oily solutions of surfactants and the preparations were classified as slightly irritant, however this effect was similar when Miglyol was applied alone. In conclusion, it is reported that the MTT assay does not correlate well with the Draize scores.
- PEGylated nanostructured lipid carriers (PEG-NLC) as a novel drug delivery system for biochanin A. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 10.:1-9.
Abstract With the aim to develop a lipid nanoparticle for biochanin A (BCA) by emulsion-evaporation and low temperature-solidification technique. The results revealed that BCA-PEG-NLC not only have small mean particle (148.5 ± 2.88 nm) with narrow polydispersity index (PI) (0.153 ± 0.01), encapsulation capacity (99.62 ± 0.06%), payload (9.06 ± 0.01%), zeta potential (-19.83 ± 1.19 mV), but also slower release rate compared with BCA suspension over 48 h by the dialysis method (n=3). The crystallinity of lipid matrix within BCA-PEG-NLC was evaluated by differential scanning calorimetry (DSC) which verified the BCA successfully into the nanoparticles. Particularly, in pharmacokinetic, the BCA-PEG-NLC of Cmax values and AUC (area under curve) was higher than BCA suspension (approximately 15.8 and 2.9 times, respectively), meanwhile, the mean residence time (MRT) was significantly longer. Furthermore, in vitro cytotoxicity BCA-PEG-NLC showed higher cytotoxicity against MCF-7 cell line compared with BCA suspension. This study suggested that PEG-NLC is a novel anti-cancer nanoparticle, which could provide attractive treatment for a wide variety of tumors and improved the oral bioavailability of poorly water-soluble drug.
- Ethylcellulose nanoparticles with bimodal size distribution as precursors for the production of very small nanoparticles. [JOURNAL ARTICLE]
- Drug Dev Ind Pharm 2014 Jul 7.:1-7.
Abstract A common technique for the preparation of polymeric nanoparticles (NPs) from preformed polymers is the emulsification solvent evaporation (ESE) method. However, the particle size of such carriers can typically not reduced below 100 nm. A bimodal distribution of particle size when applying ESE to the preparation of ethylcellulose (EC) NPs was intended to obtain very small particles in a size range below 50 nm. The proportion and size of the small particle fraction (SPF) depended on the surfactant as well as on the EC type and concentration. The preparation was conducted with different pharmaceutically relevant surfactants (polyoxyethylene (23) lauryl ether, sodium dodecyl sulfate, cetyltrimethylammonium bromide, polyvinyl alcohol and polysorbate 20) and all permitted obtaining very small NPs. After purification from excess surfactant by diafiltration and separation of the SPF by centrifugation, monodispersed particles with mean sizes between 20.6 ± 2.3 nm and 49.7 ± 4.8 nm could be isolated. The entrapment of a lipophilic model drug led to encapsulation rates between 34.0 ± 2.4% and 78.2 ± 12.6%, which were size and surfactant dependent. The preparation of polymeric NPs in a size below 50 nm by a simple centrifugation step holds promise for therapeutic applications where larger particles would be inefficient.