Liposomal hydrogel formulation for transdermal delivery of pirfenidone

Context: Pirfenidone (PFD) is an anti-fibrotic and anti-inflammatory agent indicated for the treatment of idiopathic pulmonary fibrosis (IPF). The current oral administration of PFD has several limitations including first pass metabolism and gastrointestinal irritation.

Objective: The aim of this study is to investigate the feasibility of transdermal delivery of PFD using liposomal carrier system.

Materials and methods: PFD-loaded liposomes were prepared using soy phosphatidylcholine (SPC) and sodium cholate (SC). Encapsulation efficiency (EE) of PFD in liposomes was optimized using different preparation techniques including thin film hydration (TFH) method, direct injection method (DIM) and drug encapsulation using freeze–thaw cycles. In vitro drug release study was performed using dialysis membrane method. The skin permeation studies were performed using excised porcine ear skin model in a Franz diffusion cell apparatus.

Results and discussion: The average particle size and zeta-potential of liposomes were 191?±?4.1?nm and ?40.4?±?4.5?mV, respectively. The liposomes prepared by TFH followed by 10 freeze–thaw cycles showed the greatest EE of 22.7?±?0.63%. The optimized liposome formulation was incorporated in hydroxypropyl methyl cellulose (HPMC) hydrogel containing different permeation enhancers including oleic acid (OA), isopropyl myristate (IPM) and propylene glycol (PG). PFD-loaded liposomes incorporated in hydrogel containing OA and IPM showed the greatest flux of 10.9?±?1.04?μg/cm²/h across skin, which was 5-fold greater compared with free PFD. The cumulative amount of PFD permeated was 344?±?28.8?μg/cm² with a lag time of 2.3?±?1.3?h.

Conclusion: The hydrogel formulation containing PFD-loaded liposomes can be developed as a potential transdermal delivery system.     

Preparation and characterization of a novel pH-sensitive chitosan-g-poly (acrylic acid)/attapulgite/sodium alginate composite hydrogel bead for controlled release of diclofenac sodium

A series of pH-sensitive composite hydrogel beads composed of chitosan-g-poly (acrylic acid)/attapulgite/sodium alginate (CTS-g-PAA/APT/SA) was prepared as drug delivery matrices crosslinked by Ca²⁺ owing to the ionic gelation of SA. The structure and surface morphology of the composite hydrogel beads were characterized by FTIR and SEM, respectively. pH-sensitivity of these composite hydrogels beads and the release behaviors of drug from them were investigated. The results showed that the composite hydrogel beads had good pH-sensitivity. The cumulative release ratios of diclofenac sodium (DS) from the composite hydrogel beads were 3.76% in pH 2.1 solution and 100% in pH 6.8 solutions within 24 h, respectively. However, the cumulative release ratio of DS in pH 7.4 solution reached 100% within 2 h. The DS cumulative release ratio reduced with increasing APT content from 0 to 50 wt%. The drug release was swelling-controlled at pH 6.8.     

Sustained Release of Poorly Water-Soluble Drug from Hydrophilic Polymeric Film Sandwiched Between Hydrophobic Layers

This proof-of-concept study explores the feasibility of using a drug-loaded hydrophilic polymeric layer sandwiched between two hydrophobic layers for improving film drug load while achieving sustained release of poorly water-soluble drug. Such films having total thickness in range ~?146–250 μm were prepared by slurry-based casting using hydrophilic hydroxypropyl methylcellulose (HPMC) as matrix layer containing fenofibrate (FNB) as the model drug, encased between two very thin rate-limiting layers of 10 μm each of hydrophobic poly-?-caprolactone (PCL). Film precursor slurry consisted of HPMC with plasticizer and water along with micronized FNB powders, which were dry-coated with hydrophilic silica. Characterization techniques demonstrated the presence of homogeneously dispersed crystalline FNB in films. The films are very thin and hence two-dimensional; hence, average drug load per unit area in range ~?5 to ~?9 mg/cm² could be achieved by altering the thickness of the drug matrix layer. Drug amount and drug content uniformity were measured through assay of ten circular samples ~?0.712 cm² in area punched out using a circular-shaped punch tool. Drug release rate was investigated using USP IV flow-through cell and surface dissolution imaging system. Thinner films followed Fickian diffusion, and thicker films followed non-Fickian anomalous diffusion. Overall, the application of middle layer thickness could be used as a tool to manipulate drug load without the need for altering its formulation or precursor preparation by changing its thickness, hence achieving relatively high drug loading yet having sustained release of drug.     

Atomic Fe‐Doped MOF‐Derived Carbon Polyhedrons with High Active‐Center Density and Ultra‐High Performance toward PEM Fuel Cells

A metalorganic gaseous doping approach for constructing nitrogen‐doped carbon polyhedron catalysts embedded with single Fe atoms is reported. The resulting catalysts are characterized using scanning transmission electron microscopy, X‐ray photoelectron spectroscopy, and X‐ray absorption spectroscopy; for the optimal sample, calculated densities of Fe–N_x sites and active N sites reach 1.75812 × 10¹³ and 1.93693 × 10¹⁴ sites cm^‐2, respectively. Its oxygen reduction reaction half‐wave potential (0.864 V) is 50 mV higher than that of 20 wt% Pt/C catalyst in an alkaline medium and comparable to the latter (0.78 V vs 0.84 V) in an acidic medium, along with outstanding durability. More importantly, when used as a hydrogen–oxygen polymer electrolyte membrane fuel cell (PEMFC) cathode catalyst with a catalyst loading as low as 1 mg cm^‐2 (compared with a conventional loading of 4 mg cm^‐2), it exhibits a current density of 1100 mA cm^‐2 at 0.6 V and 637 mA cm^‐2 at 0.7 V, with a power density of 775 mW cm^‐2, or 0.775 kW g^–1 of catalyst. In a hydrogen–air PEMFC, current density reaches 650 mA cm^‐2 at 0.6 V and 350 mA cm^‐2 at 0.7 V, and the maximum power density is 463 mW cm^‐2, which makes it a promising candidate for cathode catalyst toward high‐performance PEMFCs.     

Optical properties of developing pip and stone fruit reveal underlying structural changes

Analyzing the optical properties of fruits represents a powerful approach for non‐destructive observations of fruit development. With classical spectroscopy in the visible and near‐infrared wavelength ranges, the apparent attenuation of light results from its absorption or scattering. In horticultural applications, frequently, the normalized difference vegetation index (NDVI) is employed to reduce the effects of varying scattering properties on the apparent signal. However, this simple approach appears to be limited. In the laboratory, with time‐resolved reflectance spectroscopy, the absorption coefficient, μ_a, and the reduced scattering coefficient, μ_s′, can be analyzed separately. In this study, these differentiated optical properties were recorded (540–940 nm), probing fruit tissue from the skin up to 2 cm depth in apple (Malus × domestica ‘Elstar’) and plum (Prunus domestica ‘Tophit plus’) harvested four times (65–145 days after full bloom). The μ_a spectra showed typical peak at 670 nm of the chlorophyll absorption. The μ_s′ at 670 nm in apple changed by 14.7% (18.2–15.5 cm^?1), while in plum differences of 41.5% (8.5–5.0 cm^?1) were found. The scattering power, the relative change of μ_s′, was zero in apple, but enhanced in plum over the fruit development period. This mirrors more isotropic and constant structures in apple compared with plum. For horticultural applications, the larger variability in scattering properties of plum explains the discrepancy between commercially assessed NDVI values or similar indices and the absolute μ_a values in plum (R < 0.05), while the NDVI approach appeared reasonable in apple (R ≥ 0.80).     

Super‐Stretchable Zinc–Air Batteries Based on an Alkaline‐Tolerant Dual‐Network Hydrogel Electrolyte

Stretchable devices need elastic hydrogel electrolyte as an essential component, while most hydrogels will lose their stretchability after being incorporated with strong alkaline solution. This is why highly stretchable zinc–air batteries have never been reported so far. Herein, super‐stretchable, flat‐ (800% stretchable) and fiber‐shaped (500% stretchable) zinc–air batteries are first developed by designing an alkaline‐tolerant dual‐network hydrogel electrolyte. In the dual‐network hydrogel electrolyte, sodium polyacrylate (PANa) chains contribute to the formation of soft domains and the carboxyl groups neutralized by hydroxyls as well as cellulose as potassium hydroxide stabilizer are responsible for vastly enhanced alkaline tolerance. The obtained super‐stretchable, flat zinc–air battery exhibits a high power density of 108.6 mW?cm^?2, increasing to 210.5 mW?cm^?2 upon being 800% stretched. Similar phenomena are observed for the 500% stretchable fiber‐shaped batteries. The devices can maintain stable power output even after being heavily deformed benefiting from the highly soft, alkaline‐tolerant hydrogel electrolyte developed. A bendable battery‐display system and water proof weavable fiber zinc–air battery are also demonstrated. This work will facilitate the progress of using zinc–air battery powering flexible electronics and smart clothes. Moreover, the developed alkaline‐tolerant super‐stretchable electrolyte can also be applied for many other alkaline electrolyte‐based energy storage/conversion devices.     

Seasonal Dynamics of Benthic and Planktonic Algae in a Nutrient‐Rich Lowland River (Spree,Germany)

We studied chlorophyll a (chl. a), biovolume and species composition of benthic algae and phytoplankton in the eutrophic lower River Spree in 1996. The chl. a concentration was estimated as 3.5 (2.7–4.5) µg/cm² for epipsammon, 9.4 (7.4–11.9) µg/cm² for epipelon and 6.7 (5.7–7.8) µg/cm² for the epilithon (median and 95% C. L.). The mean total biomass of benthic algae was significantly higher (6.0 µg chl. a/cm²) than the areal chl. a content of the pelagic zone (1.6 µg chl. a/cm²). Although certain phytoplankton taxa were abundant in the periphyton, benthic taxa generally dominated the assemblages. Seasonal dynamics of benthic algae were probably controlled by light and nitrate supply (sand), discharge fluctuations (sand, mud) and invertebrate grazing (stones). This paper shows the importance of benthic algae even in phytoplankton‐rich lowland rivers with sandy or muddy sediments. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

FTIR spectra signatures reveal different cellular effects of EGFR inhibitors on nonsmall cell lung cancer cells

ATP‐analogue inhibitors, Gefitinib (Iressa) and Erlotinib (Tarceva) had been approved for advanced and metastatic nonsmall cell lung cancer (NSCLC) cells against tyrosine kinase domain of epidermal growth factor receptor (EGFR). Many techniques have been developed to better understand the drug mechanism which is multistep, time‐consuming and expensive. Herein, we performed Fourier‐transform infrared (FTIR) microscopy for evaluating the biochemical change on NSCLC (A549) cells after treatment. At levels that produced equivalent effects, Gefitinib dramatically induced cell apoptosis via impaired mitochondrial transmembrane potential. Whereas, Erlotinib had a slight effect on A549. Principal component analysis was performed to distinguish the effect of EGFR inhibitors on A549. FTIR spectra regions were divided into three regions: lipids (3000‐2800 cm^?1), proteins (1700‐1500 cm^?1) and carbohydrates and nuclei acids (1200‐1000 cm^?1). Biochemical changes can be evaluated by these spectral regions. This work may be a novel concept for utilizing FTIR spectroscopy for high‐throughput discriminative effects of a drug or compound and its derivatives on cells.     

Complex biopolymeric systems at stalk/epicuticular wax plant interfaces: A near infrared spectroscopy study of the sugarcane example

Naturally occurring macromolecules present at the epicuticular wax/stalk tissue interface of sugarcane were investigated using near infrared spectroscopy (NIRS). Investigations of water, cellulose, and wax‐cellulose interrelationships were possible using NIRS methods, where in the past many different techniques have been required. The sugarcane complex interface was used as an example of typical phenomena found at plant leaf/stalk interfaces. This detailed study showed that sugarcane cultivars exhibit spectral differences in the CH_n, water OH, and cellulose OH regions, reflecting the presence of epicuticular wax, epidermis, and ground tissue. Spectrally complex water bands (5276 cm^?1 and 7500–6000 cm^?1) were investigated via freeze‐drying experiments which revealed sequentially a complex band substructure (7500–6000 cm^?1), a developing weak H‐bonding system (～7301 cm^?1), and strong H‐bonding (～7062 cm^?1) assigned to water—cellulose interactions. Principal component analysis techniques clarified complex band trends that developed during the desorption experiment. Bands from wax‐free stalk were minimized in the 4327–4080 cm^?1 region (C? H_n vibrational modes associated with long chain fatty compounds), while bands from the stalk tissue (particularly lignin and moisture) became more pronounced. This work is a comprehensive guide to similar studies by scientists involved in a variety of plant and fiber research fields. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 642–651, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com     

In vitro and in vivo investigation of a novel two-phase delivery system of 2-methoxyestradiol liposomes hydrogel

For improving effectiveness of conventional chemotherapy of subcutaneous tumor, we selected 2-methoxyestradiol (2-ME) as a model drug, local injectable PLGA-PEG-PLGA copolymer thermosensitive hydrogel loading 2-ME liposomes instead of free 2-ME as a novel two-phase drug delivery system was developed, which avoid rapid clearance of liposomes follwing systemic administration. This new transport system was characterized in vitro and in vivo including rheological behavior, thermo-sensitiveness, stability, released character and intratumoral delivery. The PLGA-PEG-PLGA copolymer solution exhibited still reversible thermosensitive property and better syringeability after incorporated 2-ME liposomes. The 2-ME liposomes were demonstrated stable in the hydrogel by five methods such as scanning electron microscopy (SEM), fluorescent labeling, opalescence, particle size and ultrafiltration methods. Results showed that intact liposomes could be released from the hydrogel and following zero-order model, and sustained release one–two months in vitro and in vivo. In vivo release data demonstrating that 2-ME liposomes could be transported to tumor site, improved therapeutic efficacy and bioavailability of 2-ME liposomes in subcutaneous tumor chemotherapy.     

Thermal and Ionic Factors in the Ultraviolet Photolysis of Plant Cell Membranes

The exposure of red beet root tissue to ultraviolet (254 nm) at 2 × 10⁶ erg × cm^?2× min^?1 (0.2 J × cm^?2× min^?1) causes release of betacyanin after a 20 minute induction period. Ultraviolet-photolysis is temperature-sensitive having a thermal threshold at about 10°C. Reduction in pigment release was effected by chlorides of Mg, Ca and Sr, but not by Li, Na or K. This effect was marked but not complete, even at 40 mM concentration. It is concluded that photolysis is indirect, and involves a lytic factor, possibly an oxidant, derived from an original photochemical product.     

Two silicone nontoxic fouling release coatings: Hydrosilation cured PDMS and CaCO3 filled,ethoxysiloxane cured RTV11

Two silicone coatings have been evaluated for barnacle adhesion. One coating is an unfilled hydrosilation cured polydimethylsiloxane (PDMS) network, while the other is a room temperature vulcanized (RTV), filled, ethoxysiloxane cured PDMS elastomer, RTV11^?. The adhesion strength of one species of barnacle, Balanus eburneus, to the hydrosilation coatings is in the range of 0.37–0.60 kg cm^‐2 while the corresponding range for RTV11 is 0.64–0.90 kg cm^‐2. The easier release of B. eburneus from the hydrosilation cured network compared to RTV11 is discussed in relationship to differences in bulk and surface properties. Preliminary results suggest bulk modulus may be the most important parameter in determining barnacle adhesion strength. In light or mechanical property analysis, a re‐evaluation of surface properties and chemical stability is presented.     

Enantioselective Photolysis and Quantitative Chiral Analysis of Tryptophan Complexed With Alkali‐Metalized L‐Serine in the Gas Phase

The enantioselective photolysis of a cold gas‐phase noncovalent complex of tryptophan with alkali‐metalized L‐serine, M⁺(L‐Ser)(Trp) (M = Na and Li), was examined using a tandem mass spectrometer containing a variable‐temperature ion trap. CO₂ loss from Trp in the clusters was enantiomerically selective in ultraviolet excitation with linearly polarized light. M⁺(L‐Ser) promoted the enantioselective photolysis of Trp as a chiral auxiliary. The enantioselective photolysis of the D‐enantiomer was applied to a quantitative chiral analysis, in which the optical purity of tryptophan could be determined by measuring the relative abundance ratio R of the enantioselective CO₂ loss to the chiral‐independent evaporation of L‐Ser in a single photodissociation mass spectrum of M⁺(L‐Ser)(Trp). Chirality 27:349–352, 2015. © 2015 Wiley Periodicals, Inc.     

Synthesis of an amphiphilic tetrazine derivative and its application as a liposomal component to accelerate release of encapsulated drugs

Tetrazine irreversibly reacts with dienophiles, and its derivatives find wide applications in the fields of biochemistry and biophysics. We have synthesized an amphiphilic tetrazine derivative (2-hexadecyl-N-(6-(6-(pyridin-2-yl)-1,2,4,5-tetrazine-3-yl)pyridin-3-yl)octadecanamide; 1), which has a hydrophilic tetrazine structure and hydrophobic alkyl chains. Liposomes composed of compound 1 and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) (PTz-liposome) were prepared. In search of a new drug delivery system (DDS), we investigated the viability of inverse electron-demand Diels-Alder, a reaction between tetrazine and 2-norbornene, on the surface of the liposomes to change membrane fluidity and promote spatial and temporal controlled release of the encapsulated drugs. Compound 1 was synthesized with a yield of 71%. MS analysis after incubation of 2-norbornene with PTz-liposome revealed the binding of 2-norbornene to tetrazine. Indium-111-labeled diethylenetriaminepentaacetic acid (¹¹¹In-DTPA) was encapsulated inside PTz-liposome to evaluate the leakage of free ¹¹¹In-DTPA from the liposomes quantitatively. After 24 h of adding 2-norbornene, the release percentage for PTz-liposome was significantly higher than that for the control liposome (without tetrazine structure). Furthermore, the membrane fluidity of the PTz-liposome was increased by adding 2-norbornene. These results suggested that the combination of dienophile and liposome containing a newly synthesized tetrazine derivative can be used as a controlled release DDS carrier.     

Effect of periphyton on growth performance of grey mullet, Mugil cephalus (Linn.), in inland saline groundwater ponds

The present study attempts to assess the potential of artificial substrates to enhance fish production in inland saline groundwater ponds through periphyton production. Grey mullet, Mugil cephalus, was cultured for 100 days in ponds with substrate (treatment ponds) and without substrate (control ponds). To enhance the surface area, bamboo poles were used as substrate. The periphyton population, pigment concentration and hydrobiological characteristics of pond water were monitored. The studies revealed little difference in most of the water quality parameters observed in the two treatments. However, turbidity (27.0 ± 0.1–35.0 ± 0.1 Nephalo Turbidity Unit (NTU)), chlorophyll ‘a’ (6.6 ± 0.6–7.6 ± 0.6 μg L^?1), plankton population (phytoplankton 8.4 × 10³–9.4 ×10³ numbers L^?1; zooplankton 4.0 × 10³–5.1 × 10³ numbers L^?1) and NH₄–N (2.0 ± 0.2–2.3 ± 0.1 mg L^?1) were high in the treatment with no additional substrate; however, in the treatment with substrate the total Kjeldahl nitrogen (9.8 ± 0.8–10.8 ± 0.7 mg L^?1) and o‐PO₄ (0.1 ± 0.01–0.1 mg L^?1) remained significantly (P < 0.05) higher. Highest periphyton biomass in terms of dry matter (DM) (0.8 ± 0.01–1.4 ±0.01 mg cm^?2), ash free DM (0.4 ± 0.0–0.6 ± 0.01 mg cm^?2), chlorophyll ‘a’ (3.1 ± 0.2–8.1 ± 0.8 μg cm^?2) and pheophytin ‘a’ (1.9 ± 0.4–3.9 ± 0.5 μg cm^?2) was observed at 50 cm depth in ponds provided with additional substrate. Fifteen plankton genera showing periphytic affinity colonized the bamboo substrates. Fish growth (mean fish weight 524.3 ± 8.7 g and SGR 2.5 ± 0.1) was significantly (P < 0.05) higher in ponds provided with additional substrate compared with control ponds (387.2 ± 6.0). Length–weight relationship (LWR) (W = cLⁿ) also showed that the exponential value (‘n’) of length was high in substrate‐supported ponds (n = 2.36) in comparison with controls (n = 1.09). These studies suggest that a periphyton‐supported aquaculture system can be used successfully for the culture of herbivorous brackishwater fish species like M. cephalus in inland saline groundwaters and thus could contribute to the development of sound and sustainable aquaculture technology.     

Explication of bovine serum albumin binding with naphthyl hydroxamic acids using a multispectroscopic and molecular docking approach along with its antioxidant activity

In the present investigation, the protein‐binding properties of naphthyl‐based hydroxamic acids (HAs), N‐1‐naphthyllaurohydroxamic acid ( 1 ) and N‐1‐naphthyl‐p‐methylbenzohydroxamic acid ( 2 ) were studied using bovine serum albumin (BSA) and UV–visible spectroscopy, fluorescence spectroscopy, diffuse reflectance spectroscopy–Fourier transform infrared (DRS–FTIR), circular dichroism (CD), and cyclic voltammetry along with computational approaches, i.e. molecular docking. Alteration in the antioxidant activities of compound 1 and compound 2 during interaction with BSA was also studied. From the fluorescence studies, thermodynamic parameters such as Gibb's free energy (ΔG), entropy change (ΔS) and enthalpy change (ΔH) were calculated at five different temperatures (viz., 298, 303, 308, 313 or 318 K) for the HAs–BSA interaction. The results suggested that the binding process was enthalpy driven with dominating hydrogen bonds and van der Waals’ interactions for both compounds. Warfarin (WF) and ibuprofen (IB) were used for competitive site‐specific marker binding interaction and revealed that compound 1 and compound 2 were located in subdomain IIA (Sudlow's site I) on the BSA molecule. Conclusions based on above‐applied techniques signify that various non‐covalent forces were involved during the HAs–BSA interaction. Therefore the resulted HAs–BSA interaction manifested its effect in transportation, distribution and metabolism for the drug in the blood circulation system, therefore establishing HAs as a drug‐like molecule.     

Ultrasonography to Quantify Hepatic Fat Content: Validation by 1H Magnetic Resonance Spectroscopy

An abundance of fat stored within the liver, or steatosis, is the beginning of a broad hepatological spectrum, usually referred to as fatty liver disease (FLD). For studies on FLD, quantitative hepatic fat ultrasonography would be an appealing study modality. Objective of this study was to develop a technique for quantifying hepatic fat content by ultrasonography and validate this using proton magnetic resonance spectroscopy (¹H MRS) as gold standard. Eighteen white volunteers (BMI range 21.0–42.9) were scanned by both ultrasonography and ¹H MRS. Altered ultrasound characteristics, present in the case of FLD, were assessed using a specially developed software program. Various attenuation and textural based indices of FLD were extracted from ultrasound images. Using linear regression analysis, the predictive power of several models (consisting of both attenuation and textural based measures) on log 10–transformed hepatic fat content by ¹H MRS were investigated. The best quantitative model was compared with a qualitative ultrasonography method, as used in clinical care. A model with four ultrasound characteristics could modestly predict the amount of liver fat (adjusted explained variance 43.2%, P = 0.021). Expanding the model to seven ultrasound characteristics increased adjusted explained variance to 60% (P = 0.015), with r = 0.789 (P < 0.001). Comparing this quantitative model with qualitative ultrasonography revealed a significant advantage of the quantitative model in predicting hepatic fat content (P < 0.001). This validation study shows that a combination of computer‐assessed ultrasound measures from routine ultrasound images can be used to quantitatively assess hepatic fat content.     

Floating granules of ranitidine hydrochloride-gelucire 43/01: Formulation optimization using factorial design

The purpose of this research was to develop and optimize a controlled-release multiunit floating system of a highly water soluble drug, ranitidine HCl, using Compritol, Gelucire 50/13, and Gelucire 43/01 as lipid carriers. Ranitidine HCl-lipid granules were prepared by the melt granulation technique and evaluated for in vitro floating and drug release. ethyl cellulose, methylcellulose, and hydroxypropyl methylcellulose were evaluated as release rate modifiers. A 3² full factorial design was used for optimization by taking the amounts of Gelucire 43/01 (X ₁) and ethyl cellulose (X ₂) as independent variables, and the percentage drug released in 1(Q₁), 5(Q₅), and 10 (Q₁₀) hours as dependent variables. The results revealed that the moderate amount of Gelucire 43/01 and ethyl cellulose provides desired release of ranitidine hydrochloride from a floating system. Batch F4 was considered optimum since it contained less Gelucire and was more similar to the theoretically predicted dissolution profile (f₂=62.43). The temperature sensitivity studies for the prepared formulations at 40°C/75% relative humidity for 3 months showed no significant change in in vitro drug release pattern. These studies indicate that the hydrophobic lipid Gelucire 43/01 can be considered an effective carrier for design of a multiunit floating drug delivery system for highly water soluble drugs such as ranitidine HCl. Published: April 13, 2007     

Effect of Formulation Parameters on the Preparation of Superporous Hydrogel Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Carvedilol

The purpose of this study was to formulate a superporous hydrogel (SPH) containing carvedilol self-nanoemulsifying drug delivery system. Effects of formulation parameters (amount of SPH and 0.1 N HCl used during drug loading) were studied in 3² factorial design. Response surface plots showed significant effect of the parameters on hydrogel swelling, carvedilol content, and carvedilol in vitro release. Regression equations were generated to calculate the desirable responses.     

Development and evaluation of a diatom-conductivity model from lakes in West Greenland

1. The area around Kangerlussuaq (Søndre Strømfjord; West Greenland, 67°N 51°W) contains thousands of lakes ranging from coastal, dilute (conductivity < 30 μS cm^–1) oligotrophic systems to subsaline (～4000 μS cm^–1), closed basin lakes close to the ice sheet margin. In closed basins, salinity (or conductivity) is often a proxy for effective moisture, and thus palaeorecords of lake conductivity can provide valuable palaeoclimatic data. Little or nothing is known about the recent history of these lakes and hence it is difficult to evaluate how they will respond to effects of future changes. 2. Over 100 lakes have been sampled (1996–2000) between the ice sheet and the outer coast for a variety of water chemical and limnological variables. Surface sediments were taken from a subset of 40 lakes and analysed for diatoms. Diatom responses to 28 environmental variables were analysed by multivariate ordination techniques and indicate that the main gradient is highly correlated to conductivity (explaining ～12% of species variance). Despite the relatively short gradient (24–4072 μS cm^–1), diatom assemblages exhibit a clear response to conductivity. The most saline lakes do not contain a true saline flora. 3. We developed a range of weighted averaging (WA) and weighted‐averaging partial least squares (WA‐PLS) models from this training data set and found two component WA‐PLS models performed best. The effects of data transformation and omission of dissolution susceptible species (Diatoma spp.) on model performance were also examined. The error statistics for the preferred WA‐PLS (2) model (r²_jack=0.88, root mean square error of prediction (RMSEP)=0.217 log μS cm^–1) compare well with other published models. 4. A ²¹⁰Pb‐dated short core from a meromictic, subsaline lake (Braya Sø; location 67°N, 51°W, max. depth 23 m; conductivity 2600 μS cm^–1) was analysed for diatoms. Diatom preservation is poor and some taxa (e.g. Diatoma spp.) are badly corroded. Lake water conductivity was reconstructed using WA‐PLS models. Diatom‐inferred conductivity ranges from 1800 to 4400 μS cm^–1 over the last 600 years (extrapolated ²¹⁰Pb chronology). 5. The Kangerlussuaq area of West Greenland is an important area for palaeoclimatic research, located as it is between the Greenland ice sheet (ice core records) and the Davis Straits to the west. The development of a statistically robust transfer function for diatoms and conductivity will enable the reconstruction of conductivity from the many subsaline lakes around the head of the fjord and, hence, regional estimates of changing palaeoprecipitation.