Showing papers in "Pharmaceutical Development and Technology in 2014"
TL;DR: Evaluating the application of mannitol in comparison to other common fillers/binders found it to have many strong advantages which can be expected to result in a more widespread application in the near future.
Abstract: Various fillers/binders which are applied for the formulation of solid oral dosage forms are assessed for their benefits and drawbacks, including lactose, sorbitol, mannitol, microcrystalline cellulose and calcium hydrogen phosphate dihydrate. A focus of this work was to evaluate the application of mannitol in comparison to other common fillers/binders as it was observed that this excipient is gaining more and more attention in pharmaceutical formulation development and production. While one of the main advantages of conventional fillers/binders such as lactose, microcrystalline cellulose and calcium hydrogen phosphate dihydrate is their low price level, mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the API and the patient's body, its good compactibility and the ability to produce extremely robust tablets. Additionally, the suitability of mannitol for the emerging formulation technology of orally disintegrating tablets is pointed out. In summary, it is emphasized that the selection of the filler/binder is highly individual, depending, for example, on the preferred characteristics of the final solid dosage form, the applied API and the available budget. However, mannitol exhibits many strong advantages which can be expected to result in a more widespread application in the near future.
117 citations
TL;DR: Overall, polymers proved to be crystallization inhibitors, but inhibition was limited due to the intramolecular hydrogen bonding in curcumin, which leads to a decrease in the ability of the polymers to interact at a molecular level.
Abstract: We have investigated the physical stability of amorphous curcumin dispersions and the role of curcumin-polymer intermolecular interactions in delaying crystallization. Curcumin is an interesting model compound as it forms both intra and intermolecular hydrogen bonds in the crystal. A structurally diverse set of amorphous dispersion polymers was investigated; poly(vinylpyrrolidone), Eudragit E100, carboxymethyl cellulose acetate butyrate, hydroxypropyl methyl cellulose (HPMC) and HPMC-acetate succinate. Mid-infrared spectroscopy was used to determine and quantify the extent of curcumin-polymer interactions. Physical stability under different environmental conditions was monitored by powder X-ray diffraction. Curcumin chemical stability was monitored by UV-Vis spectroscopy. Isolation of stable amorphous curcumin was difficult in the absence of polymers. Polymers proved to be effective curcumin crystallization inhibitors enabling the production of amorphous solid dispersions; however, the polymers showed very different abilities to inhibit crystallization during long-term storage. Curcumin intramolecular hydrogen bonding reduced the extent of its hydrogen bonding with polymers; hence most polymers were not highly effective crystallization inhibitors. Overall, polymers proved to be crystallization inhibitors, but inhibition was limited due to the intramolecular hydrogen bonding in curcumin, which leads to a decrease in the ability of the polymers to interact at a molecular level.
82 citations
TL;DR: The size and EE of vancomycin nanoparticles were optimized by the proposed procedure, which is a promising approach to overcome antibiotic-resistance.
Abstract: Context: Treating vancomycin-resistant Staphylococcus aureus strains requires high doses of vancomycin, which might lead to adverse reactions such as nephrotoxicity and “red neck syndrome”. Use of nanotechnology for antibiotic delivery is a promising approach to overcome antibiotic-resistance.Objective: The objective of this study was optimizing the particle size and encapsulation efficiency (EE) of vancomycin nanoparticles prepared from chitosan.Materials and methods: The nanoparticles were prepared by ionotropic gelation method, at different combinations of chitosan concentration, chitosan/tripolyphosphate mass and vancomycin/chitosan mass, using Box–Behnken experimental design. Dynamic light scattering and ultracentrifugation were used to measure the nanoparticle size and EE, respectively. Vancomycin was quantified in samples by spectrophotometery. The optimum conditions were determined by subsequent regression analysis and multicriteria decision analysis of the output data.Results: The nanopar...
56 citations
TL;DR: It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application as shown in the results of this study.
Abstract: Objective: The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX).Materials and methods: The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application.Results and discussion: The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430 nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of −19.1 to −25.7 mV. The release profiles of all formulations exhibited sustained release characteristics over 48 h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorpora...
56 citations
TL;DR: Binary solid dispersions enhanced the dissolution rate of nisoldipine to formulate fast disintegrating tablets with rapid dissolution and indicated that the SD enhanced dissolution is not due to the solubilizing effect of the polymer and can be due to physical change in the drug crystal.
Abstract: Nisoldipine is a calcium channel blocker with low and variable oral bioavailability. This was attributed to slow dissolution and presystemic metabolism. Accordingly, the objective of this work was to enhance the dissolution rate of nisoldipine to formulate fast disintegrating tablets with rapid dissolution. Binary solid dispersions (SD) were prepared for the drug with hydroxypropyl methyl cellulose E5 (HPMC), polyvinylpyrrolidone (PVP), Pluronic F68 or polyethylene glycol 6000 (PEG 6000). SD formation increased the dissolution rate compared to pure drug with the corresponding physical mixtures failing to provide the same dissolution enhancement. This indicates that the SD enhanced dissolution is not due to the solubilizing effect of the polymer and can be due to physical change in the drug crystal which was confirmed by thermal analysis. SD with HPMC and PVP were selected for preparation of fast disintegrating tablets as they liberated most of the drug in the first 5 min. HPMC-based tablets disint...
55 citations
TL;DR: Higher carvedilol uptake from SLNs compared to drug solution in the Caco-2 cell line exhibited a potential prolonged drug release and upon cellular uptake, SLNs could then enter the lymphatic system which will avoid first pass metabolism and hence higher oral bioavailability.
Abstract: Carvedilol-loaded solid lipid nanoparticles (SLNs) were prepared using solubility parameter (δ) to select the lipid, and hot homogenization to fabricate SLNs. The effect of concentration of Compritol 888 ATO (COMP) and Poloxamer 188 (P-188) on the particle size of blank SLNs was studied using the design of experiments. Further narrow concentration range of COMP and P-188 was selected and carvedilol-loaded SLNs were prepared to obtain an optimized formulation which was lyophilized (L-SLNs), transformed into enteric compression-coated tablet and evaluated for drug release, X-ray diffraction and cellular uptake mechanism. COMP was chosen as lipid due to its least value of Δδ with carvedilol. The optimized formulation (7.5% COMP, 5.0% P-188 and 1.11% carvedilol) had 161 nm particle size and 94.8% entrapment efficiency. The enteric-coated carvedilol-loaded SLNs tablet protected carvedilol from acidic environment and similar prolonged release profiles were obtained from L-SLNs, core tablet and enteric-c...
54 citations
TL;DR: The results of these studies demonstrated immense potential of the topically applied TAM-encapsulated vesicular and micellar systems in psoriasis, thus calling for more comprehensive investigations to establish the role of TAM in the management of Psoriasis.
Abstract: Objective: Tamoxifen (TAM) is widely employed in the treatment of breast malignancies and is also found to be effective in psoriasis treatment. The current studies aimed to explore the antipsoriatic potential of topical TAM encapsulated in the new generation phospholipid-based vesicular and micellar systems, i.e. flexible membrane vesicles (FMVs) and pluronic lecithinized organogels (PLOs).Methods: TAM-loaded-FMVs were prepared by thin-film hydration technique, while TAM–PLOs were prepared by simple mixing. Mouse-tail model was used to evaluate the antipsoriatic activity of the novel formulations. The mouse tails were treated once-a-day with different formulations for a period of four weeks and prepared for longitudinal histological sections by hematoxylin–eosin staining technique. The length of the orthokeratotic regions in stratum granulosum was measured on 10 sequential scales per tail section as percentage of the full length of the scale, and the drug activity was calculated further.Results: E...
47 citations
TL;DR: The developed rutin-loaded nanoemulsion proved to be stable and suitable to encapsulating poorly water-soluble drugs and showed a sustained release profile.
Abstract: The aim of the present study is to design and characterize a rutin-loaded nanoemulsion (RT-NE) and determine the release profile of the drug in vitro. RT-NE was prepared by a high pressure homogenization technique. The obtained droplets were analyzed by optical microscopy and were shown to be of spherical shape. By dynamic light scattering, characterization of RT-NE showed an average diameter of 127 nm, polydispersity index of 0.168 and zeta potential values near neutrality (−3.49 mV). Encapsulation efficiency was of ∼82% (82.3 ± 1.62%). Drug release was characterized by an initial burst which decreased over the time, showing a sustained release profile. After 24 h, rutin released from NE reached nearly 65%. The developed system proved to be stable and suitable to encapsulating poorly water-soluble drugs.
45 citations
TL;DR: Such injectable thermosensitive hydrogel of etoposide could be effectively used for continuous release of drug to the tumor and surrounding tissues.
Abstract: Context: Hydrogels are promising polymeric network capable of sustaining the release of drug but have a major limitation for encapsulation of hydrophobic drugs.Objective: This study was undertaken to encapsulate etoposide in poloxamer 407-based thermosensitive hydrogels with an aim to sustain its release.Materials and methods: Etoposide-loaded hydrogels were prepared by the cold method and optimized for encapsulation efficiency (EE) by a 32 factorial design. Poloxamer 407-poloxamer 188 hydrogel (E-P407-P188) and poloxamer 407-poly(ethylene glycol) (E-P407-PEG) hydrogel were characterized for SEM, swelling, sol–gel phase transition and injectability study.Results and discussion: In E-P407-P188 hydrogel the EE of 75% could be obtained and in E-P407-PEG hydrogels the EE was 84%. The SEM images showed a porous structure. The release of ETO was sustained up to 48 h by E-P407-PEG hydrogel and 24 h by E-P407-P188 hydrogel. The drug release was governed by first-order kinetics and followed Fickian diffusi...
43 citations
TL;DR: Pulse frequency and time were found to be critical for obtaining SLNs with desirable size, whereas the stability of the SLNs was dependent on their lipid content.
Abstract: The objective of this study was to evaluate the effect of sonication time and pulse frequency on average dispersion temperature (ART), particle size and zeta potential of solid lipid nanoparticles (SLNs). A two-factor, three-level response surface methodology (RSM) was used to optimize sonication time between 5 and 15 min and pulse frequency from 30 to 90%. SLNs made from stearyl alcohol (SA) and cetyl trimethylammonium bromide (CTAB) blend at 1:3 ratio were prepared by applying high-shear homogenization and sonication. Pulse frequency and time were found to have a significant effect on particle size and ART. The effect of sonication parameters on zeta potential, however, was insignificant. The optimal sonication parameters for preparing 100 nm SLNs made from a SA/CTAB blend was 60% pulse frequency at 40% power for 10 min. Optimized sonication parameters were then used to investigate the effect of lipid type on SLN size and zeta potential. The mean particle sizes of SLNs made with SA, cetyl palmit...
41 citations
TL;DR: The development, evaluation and application of lung-targeted drug delivery systems via intravenous administration for the treatment of lung diseases reported in the past decades are reviewed.
Abstract: The treatment of lung diseases including lung cancer and tuberculosis is one of the most challenging problems in clinical practice, because the conventional drug delivery systems cannot deliver drug effectively to the lung, which result in low therapeutic effect. Therefore, lung-targeted drug delivery systems (LTDDS) that can deliver drug to the lung in an effective way to increase drug concentration in lung tissue and reduce drug distribution in other organs and tissues become an ideal strategy to treat lung diseases. The LTDDS mainly include microparticles (microspheres and microencapsules), liposomes and nanoparticles via intravenous administration, and dry powder carriers and nebulized suspensions via pulmonary inhalation. As lungs possess the large absorptive surface area, the low thickness of the epithelial barrier and good blood supply, pulmonary inhalation has received great attention. Intravenous route is the commonly practiced method for administration of larger doses of drugs into the body. Numerous drugs can be delivered directly into general circulation by avoiding their first-pass metabolism and have potential to transport drugs to the lung via intravenous administration. This present article reviews the development, evaluation and application of LTDDS via intravenous administration for the treatment of lung diseases reported in the past decades.
TL;DR: Ethylcellulose microparticles containing metronidazole and propolis extractive solution were prepared and evaluated in vitro against periodontal pathogens and showed potential for developing intermediary or eventual dosage form to be administered into theperiodontal pocket more easily and safely.
Abstract: Ethylcellulose microparticles containing metronidazole and propolis extractive solution were prepared and evaluated in vitro against periodontal pathogens. Scanning electron microscopy, particle size analysis, drug entrapment efficiency and drug release of microparticles were determined. The antimicrobial activity of microparticles was evaluated against microorganisms of periodontal importance (Enterococcus faecalis, Streptococcus pyogenes, Streptococcus mutans, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli). It was obtained particles with regular morphology, mean diameter of 1.23 µm, and entrapment efficiency for propolis and metronidazole were 91.41% and 22.23%, respectively. In vitro release studies of propolis and metronidazole from microparticles showed prolonged drug release and controlled by Fickian diffusion. Both propolis and metronidazole displayed activity against the tested strains. Moreover, the results showed that the strains of E. faecalis, S. pyogenes and S. mutans were more susceptible to the propolis and E. faecalis to the metronidazole. It was also observed that the amount of metronidazole to inhibit the microorganism strains in the physical mixture with propolis was smaller than in the metronidazole alone, suggesting potentiation effect between propolis and metronidazole. These microparticles would be useful for developing intermediary or eventual dosage form to be administered into the periodontal pocket more easily and safely.
TL;DR: It can be concluded that both the SLNs and NLCs are promising dermal drug delivery systems for ATRA.
Abstract: The objective of this study was to investigate the effects of drug amounts (0.1%, 0.2% and 0.3% w/w), amounts of the oil (10%, 15% and 20% w/w of lipid matrix) and types of the oil (soybean oil (S), medium chain triglycerides (M), oleic acids (O) and linoleic acids (L)) in lipid matrix of all-trans retinoic acid (ATRA)-loaded nanostructured lipid carriers (NLCs) for transdermal drug delivery. The ATRA-loaded solid lipid nanoparticles (SLNs) were formulated with 30% w/w cetyl palmitate. All lipid nanoparticles had average sizes between 130 and 241 nm and had negative zeta potentials. The drug loading of all formulations was higher than 95%. The release of drug from all lipid nanoparticles followed zero-order kinetics. The amount of drug released from all the NLCs and SLNs was significantly greater than the drug released from the ATRA suspension. The ATRA flux of the SLNs was higher than the NLCs. The flux of the NLCs containing oleic acid was significantly higher than the other types of oils. The c...
TL;DR: Evidence is provided that poloxamer 407 is a promising polymer not only for sustained delivery of IL-1Ra but also provides conformational stability for extended time.
Abstract: Sustained delivery of proteins from polymer-based thermosensitive gel has achieved considerable attention since last decade. In our previous work, we developed a formulation for sustained delivery of IL-1Ra-loaded poloxamer 407 formulation and investigated its in vitro and in vivo characteristics. In the present work, we extended this approach to investigate stability of IL-1Ra from poloxamer 407 formulation stored at 4 °C, 25 °C and 40 °C for 3 months. Samples were taken and in vitro drug release kinetics was studied. Percent of drug content was measured using the BCA method. DSC and SDS-PAGE were used to assess the conformational stability of IL-1Ra. FTIR spectroscopy was performed to investigate the drug–polymer interaction. From the results, it was found that gelation temperature, viscosity and in vitro release pattern of IL-1Ra from poloxamer 407 formulation at 4 °C were almost same throughout the stability study period. DSC profiles of IL-1Ra loaded in poloxamer 407 formulation increased the...
TL;DR: The presented data revealed the superiority of using probe sonication besides high pressure homogenization during the formation of secondary emulsion, and indicated that the tested factors had a pronounced significant effect on the EE%.
Abstract: Poly lactic-co-glycolic acid (PLGA 502 H) nanoparticles incorporating ciprofloxacin HCl (CP) were prepared by double emulsion solvent diffusion technique.Methods: The influence of the application of probe sonication besides the high pressure homogenization in the preparation of the secondary emulsion and its application during the solidification step were studied. Their effect on the particle size, Zeta potential and the percent encapsulation efficiency of the drug (EE %) were investigated. The effect of the addition of polyvinyl alcohol (PVA) during the preparation of the primary emulsion was studied. Moreover, the effect of the addition of 0.1 M sodium chloride and/or adjusting the external and extracting phases to pH 7.4 were investigated. The selected formula was examined using IR, X-ray, DSC and SEM and in vitro drug release.Results: These formulations showed an appropriate particle size ranges between 135.7–187.85 nm, a mean zeta potential ranging from −0.839 to −6.81 mV and a mean EE% which...
TL;DR: Electrospun fibers with 20% plai oil loading provided the controlled release and also showed the highest plaiOil content, suggesting this electrospun nanofiber has a potential for use as an alternative topical application.
Abstract: The aim of this study was to prepare electrospun polyvinylpyrrolidone (PVP)/2-hydroxypropyl-β-cyclodextrin (HPβCD) nanofiber mats and to incorporate plai oil (Zingiber Cassumunar Roxb) The plai oil with 10, 20 and 30% wt to polymer were incorporated in the PVP/HPβCD solution and electrospun to obtain nanofibers The morphology and structure of the PVP and PVP/HPβCD nanofiber mats with and without the plai oil were analyzed using scanning electron microscopy (SEM) The thermal behaviors of the nanofiber mats were characterized using differential scanning calorimeter (DSC) Terpinen-4-ol was used as a marker of the plai oil The amount of plai oil remaining in the PVP/HPβCD nanofiber mats was determined using gas chromatography-mass spectoscopy (GC-MS) The SEM images revealed that all of the fibers were smooth The average diameter of fibers was 212–450 nm, and decreased with the increasing of plai oil content The release characteristics of plai oil from the fiber showed the fast release followe
TL;DR: Microemulsion formulations exhibited statistically significant increase in diclofenac permeation compared to oily solution, aqueous solution and oil–Smix solution, and higher skin permeation of dicL ofenac was observed with low Smix concentration and smaller droplet size.
Abstract: The objective of the present investigation was to enhance skin permeation of diclofenac using water-in-oil microemulsion and to elucidate its skin permeation mechanism. The w/o microemulsion formulations were selected based on constructed pseudoternary phase diagrams depending on water solubilization capacity and thermodynamic stability. These formulations were also subjected to physical characterization based on droplet size, viscosity, pH and conductivity. Permeation of diclofenac across rat skin using side-by-side permeation cells from selected w/o microemulsion formulations were evaluated and compared with control formulations. The selected w/o microemulsion formulations were thermodynamically stable, and incorporation of diclofenac sodium into microemulsion did not affect the phase behavior of system. All microemulsion formulations had very low viscosity (11–17 cps) and droplet size range of 30–160 nm. Microemulsion formulations exhibited statistically significant increase in diclofenac perme...
TL;DR: It is concluded that coprocessing tapioca starch and mannitol will enhance the flow, packing and compaction properties of the novel excipient and that the co-fusion method of coprocessioning would produce novel excipients with enhanced direct compression potential compared to the co,grinding method.
Abstract: Novel multifunctional excipients were prepared by coprocessing tapioca starch with mannitol using two methods viz; co-grinding and co-fusion. The flow, packing and compaction properties of the native and novel excipients were evaluated by using density, Hausner’s ratio, angle of repose, the maximum volume reduction, consolidation index, the rate of consolidation, angle of internal friction, morphological properties, Heckel analysis, tensile strength and dilution potential as evaluation parameters. The study revealed that the method of coprocessing, particle size and particle shape influenced the properties of the resulting novel excipients. Co-grinding was less effective than co-fusion in the preparation of excipients with enhanced properties. The study concluded that coprocessing tapioca starch and mannitol will enhance the flow, packing and compaction properties of the novel excipient and that the co-fusion method of coprocessing would produce novel excipients with enhanced direct compression po...
TL;DR: The experimental evidence in this research leads to the conclusion that polymeric micelles present enabling properties for oral delivery of drugs with low solubility.
Abstract: This work aimed to incorporate Dexibuprofen (DXI), the pharmacologically active and more potent form of ibuprofen, into polymeric micelles based tablets with enhanced oral bioavailability. Thin film hydration technique was employed to prepare DXI polymeric micelles using Pluronic® F127 and/or P123 solutions in different ratios (ranging from 1:1 up to 1:10). Prepared micelles were characterized regarding particle size, drug loading and entrapment efficiency. Selected formulae were lyophilized in presence of cryoprotectants and subjected to solid-state characterization as well as scanning and transmission electron microscopy. Subsequently, tablets were prepared and evaluated in-vitro regarding physical properties and drug release. An in-vivo pharmacokinetic study was performed in six healthy human volunteers in comparison to the commercially available tablet of DXI. Solid-state characterization proved that DXI was homogenously dispersed in Pluronic micelles’ matrices. Formula TF5 tablets comprising ...
TL;DR: Although Psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.
Abstract: Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12 h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12 h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release. © 2014 Informa Healthcare USA, Inc.
TL;DR: The obtained results suggest that incorporation of the poorly water-soluble drug TC in SLN preserves the in vitro antitumor activity and significantly enhance oral bioavailability of TC in rats.
Abstract: The objective of this study was to evaluate the influence of solid lipid nanoparticles (SLN) loaded with the poorly water-soluble drug tamoxifen citrate (TC) on the in vitro antitumor activity and bioavailability of the drug. TC-loaded SLN were prepared by solvent injection method using glycerol monostearate (GMS) or stearic acid (SA) as lipid matrix. Poloxamer 188 or tween 80 were used as stabilizers. TC-loaded SLN (F3 and F4) prepared using GMS and stabilized by poloxamer 188 showed highest entrapment efficiency % (86.07 ± 1.74 and 90.40 ± 1.22%) and reasonable mean particle sizes (130.40 ± 9.45 and 243.80 ± 12.33 nm), respectively. The in vitro release of TC from F3 and F4 exhibited an initial burst effect followed by a sustained drug release. In vitro cytotoxicity of F3 against human breast cancer cell line MCF-7 showed comparable antitumor activity to free drug. Moreover, the results of bioavailability evaluation of TC-loaded SLN in rats compared to free TC indicated that 160.61% increase in ...
TL;DR: It is confirmed that trehalose is among the most suitable cryoprotectant for SLN, however it did not improve shelf-life of the most stable formulation.
Abstract: Objective: To prepare stable and easy to handle formulation of solid lipid nanoparticles (SLNs) by freeze-drying with or without cryoprotectants, as appropriate.Materials and methods: SLNs were freeze-dried without cryoprotectants or with cryoprotectants in quantities selected by freeze–thaw test (sucrose, glucose) or literature search (trehalose, maltose). Appearance, re-dispersability and size distribution of re-dispersed samples were evaluated.Results: SLN could be freeze-dried using 10% sucrose, trehalose or maltose. Trehalose was effective in protecting one of presented formulations that was already very stable on its own; its efficiency in protecting other two formulations was limited.Discussion: Our results are in line with various reports of successful freeze-drying of SLN, but considering the stability of original dispersions, no improvement was achieved.Conclusion: We confirmed that trehalose is among the most suitable cryoprotectant for SLN, however it did not improve shelf-life of the ...
TL;DR: In vitro studies using Caco-2 cells revealed that lutein-loaded SNEDDS showed shorter lag time and greater (2-fold) cellular accumulation compared with the lutenin dispersion.
Abstract: A self-nanoemulsifying drug delivery system (SNEDDS) has been developed for enhanced oral bioavailability of lutein. Its permeation enhancement has been evaluated using monolayers of Caco-2 cells. SNEDDS is composed of a mixture of Lexol® and Emulmetik® 900, Labrasol®, and Tween 80 as oil, surfactant and co-surfactant, respectively. Upon dilution of lutein-loaded SNEDDS with water, a nanoemulsion was obtained in <10 s with spherical droplets of 40–150 nm in diameter. The zeta potential was in the range of −19 to −32 mV. Increasing the ratio of surfactant to co-surfactant decreased the mean droplet size. Dissolution studies showed that lutein was released rapidly (<5 min) from SNEDDS into 0.1 N HCl and pH 6.8 phosphate buffer solution without any aggregation. In vitro studies using Caco-2 cells revealed that lutein-loaded SNEDDS showed shorter lag time and greater (2-fold) cellular accumulation compared with the lutein dispersion.
TL;DR: A soft sensor that can be effectively used for in-line monitoring of the primary drying step of a pharmaceuticals freeze-drying process in vials and it allows using model-based tools for cycle development in lab-scale units and for process monitoring in industrial-scale freeze-dryers, in case wireless sensors are used.
Abstract: Purpose: This paper presents a soft sensor that can be effectively used for in-line monitoring of the primary drying step of a pharmaceuticals freeze-drying process in vials.Methods: Process modeling and product temperature measurements are used to estimate the residual amount of ice in the vial and the heat transfer coefficient from the shelf to the product in the vial. The resistance of the dried cake to vapor flow is determined through the heat balance equation at the interface of sublimation. Mathematical simulation and experimental tests have been carried out to validate the estimations provided by the soft sensor.Results: Accurate estimations of the dynamics of the product until the end of primary drying are obtained, as well as of the heat and mass transfer coefficients, even in the case of a highly non-uniform batch. The reduction in the number of variables directly estimated by the soft sensor allows increasing the robustness of the tool with respect to other sensors presented in the lite...
TL;DR: The nanosuspension was effective in prolonging life in two separate xenograft orthotopic murine cancer models through two separate routes of administration and was well-tolerated and at least as effective as the IV Taxol control.
Abstract: Objective: The purpose of this work was to prepare a stable paclitaxel nanosuspension and test it for potential use as a targeted chemotherapeutic. Different particle coatings were employed to assess their impact on cellular uptake in vitro. In vivo work was then performed to demonstrate efficacy in tumor-bearing mouse models.Materials and method: Paclitaxel nanosuspensions were prepared using a homogenization process and coated with excipients. Surface charge was measured by zeta potential, potency by high-performance liquid chromatography, and solubility using an in-line UV probe. Cellular uptake studies were performed via flow cytometry. In vivo experiments were performed to determine residence time, maximum tolerated dose, and the efficacy of paclitaxel nanosuspensions (Paclitaxel-NS).Results: A stable paclitaxel nanosuspension was prepared and coated with various excipients. Studies in mice showed that the nanosuspension was well-tolerated and at least as effective as the IV Taxol control in ...
TL;DR: In vitro release and in vivo efficacy studies revealed that the microspheres were effective in prolonging the drug’s presence in cul de sac with improved therapeutic efficacy.
Abstract: The use of mucoadhesive biopolymers is one of the best approaches to prolong the drug residence inside the cul-de-sac, consequently increasing the bioavailability. Thus, the focus of this work was to develop mucoadhesive microspheres to overcome the limitations of ocular drug delivery. The chitosan-sodium alginate microspheres of azelastine hydrochloride were fabricated using modified ionotropic gelation technique. The particle size, zeta potential, entrapment efficiency and drug release kinetics were evaluated and characterized by SEM, FT-IR, DSC, in vitro mucoadhesion and in vivo study. The microspheres had average particle size in the range of 3.55 to 6.70 µm and zeta potential +24.55 to +49.56 mV. The fabricated microspheres possess maximum drug entrapment of 73.05% with 65% mucin binding efficiency and revealed a controlled release over the 8-h period following a non-Fickian diffusion. SEM showed that microspheres were distinct solid with irregular shape. FT-IR and DSC results concluded the drug entrapment into microspheres. In vivo studies on ocular rat model revealed that azelastine microspheres had better efficacy. Chitosan sodium alginate microspheres prepared were in particle size range suitable for ocular purpose. In vitro release and in vivo efficacy studies revealed that the microspheres were effective in prolonging the drug's presence in cul de sac with improved therapeutic efficacy.
TL;DR: An optimum ratio between naproxen sodium granules and Eudragit® E was found to be 1:1.576, where less naproxin sodium was released than the threshold bitter value and an appropriate taste masking for more than 5 min was guaranteed.
Abstract: The taste of oral dosage forms is an important argument regarding patient’s compliance and acceptability. For this reason, it is often necessary to mask an undesirable and unpleasant taste of an active pharmaceutical ingredient. The purpose of this study was to mask the taste of naproxen sodium by a new fluid-bed coating approach. Different compositions of coating suspensions were used to coat naproxen sodium granules. It was found that products with the addition of a plasticizer were not stable at 40 °C and tended to agglomerate. Subsequently, formulations without plasticizer were used and the ratio between water and Eudragit® E was varied. Increasing the fraction of water in the suspension from 3% to 14% reduced the effective release of naproxen sodium. An optimum ratio between naproxen sodium granules and Eudragit® E was found to be 1:1.576, where less naproxen sodium was released than the threshold bitter value and an appropriate taste masking for more than 5 min was guaranteed. Investigation ...
TL;DR: Rats have inherent licking behavior and responses to good and aversive tasting stimuli, which are comparable to humans, and rat behavioral avoidance model can be considered as a good alternative to taste assessment by human volunteers for further such investigations.
Abstract: Rats have inherent licking behavior and responses to good and aversive tasting stimuli, which are comparable to humans Taste masking of chewable and orodispersible tablets of an iron EDTA complex salt was evaluated using rat behavioral avoidance model, brief access test Taste-masked chewable and orodispersible tablets of iron EDTA complex were prepared using various flavors and sweeteners as taste-masking agents These formulations were presented to rats and their responses were recorded in terms of licking frequency and other avoidance responses Formulations were also presented to human volunteers and a correlation between responses of humans and rats was tried to be established Taste responses of rats were found to be similar to those of humans A high correlation between the taste responses of rats and humans was observed Evaluation of taste masking using human panels presents several difficulties such as ethical concerns, fatigue and subjectivity Thus, rat behavioral avoidance model can be considered as a good alternative to taste assessment by human volunteers for further such investigations
TL;DR: The composition of the nanovesicle played an important role in physical properties and drug permeation and also contribute towards stability and non-irritancy in transdermal formulations containing permeation enhancer.
Abstract: Context: Transdermal formulations contain permeation enhancer which causes skin damage. Ceramide 2 is natural lipid found in stratum corneum (SC).Objective: Drug-loaded nanovesicles of ceramide-2, cholesterol, palmitic acid, cholesteryl sulfate were formulated and analyzed for physical and biological properties. Diclofenac was used as a model drug.Materials and method: The vesicles were prepared using the film hydration method and characterized for physical parameters, in vitro drug release, accelerated stability studies and formulated into gel. Respective gels were compared with a commercial formulation (CEG) and plain carbopol gel (CG) containing drug for ex vivo, in vivo drug permeation and anti-inflammatory activity.Results: The vesicles were stable with optimum physical parameters. DCG-1 showed 92.89% in vitro drug release. Ceramide vesicles showed drug release between 18 and 25 μg/cm2 whereas CG and CEG released 0.33 and 1.35 μg/cm2 drug, respectively. DCG-1 and CEG showed corresponding Cmax...
TL;DR: Formulations presented appropriate physicochemical characteristics and suitability for ocular application and the contact lens remained transparent and ion-permeable after association with the formulation.
Abstract: Context: The non-invasive ophthalmic therapy has a drawback: low residence time in the eye socket. Nanoparticles and contact lenses have been studied as promising ocular drug delivery systems.Objective: To develop a nanoemulsion and evaluate its compatibility with a soft contact lens as a potential strategy for ocular delivery.Materials and methods: The formulations were developed by spontaneous emulsification and fully characterized. Two drops of nanoemulsion were instilled on the surface of a commercial contact lens and its transparency was measured using a UV-Vis spectrophotometer. Before and after the instillation of the drops, the morphology (scanning electron microscopy – SEM) and ion permeability of the lenses were analyzed.Results: The formulations had a mean particle size of 234 nm, polydispersity below 0.16, zeta potential of −8.56 ± 3.49 mV, slightly acid pH, viscosity ≈1.2 mPa s−1 and spherical-shaped particles. Nanoemulsion was non-irritant (hen’s egg test-chorioallantoic membrane), w...