Phyto-cosmeceutical gel containing curcumin and quercetin loaded mixed micelles for improved anti-oxidant and photoprotective activity.

Ultra Violet radiations induced skin damage and associated skin disorders are a widespread concern. The consequences of sun exposure include a plethora of dermal conditions like aging, solar urticaria, albinism and cancer. Sunscreens provide effective protection to skin from these damages. Besides FDA approved physical and chemical UV filters, phytoconstituents with their multi functionalities are emerging as frontrunners in Therapy of skin disorders. Objective of this study was to develop novel phyto-dermal gel (PDG) with dual action of sun protection and antioxidant potential using polymeric mixed micelles (PMMs) are nanocarriers. PMMs of Pluronic F127 and Pluronic F68 loaded with curcumin and quercetin were optimized by 32 factorial designs. Responses studied were vesicle size, SPF, entrapment efficiency of curcumin and quercetin and antioxidant activity. Droplet size ranged from 300 to 500 nm with PDI in between 0.248 and 0.584. Combination of curcumin and quercetin showed enhanced sun protection and antioxidant activity. Pluronics played a significant positive role in various parameters. In present studies vesicle size of factorial batches was found to be between 387 and 527 nm, and SPF was found to be between 18.86 and 28.32. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into Carbopol 940. Optimized PDG was evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and skin retention. Hysteresis loop in the rheogram suggested thixotropy of PDG. Syneresis for gels from day 0-30 days was found to be between 0% and 12.46% w/w. SPF of optimized PDG was 27±0.5. Optimized PDG showed no signs of erythema and edema on Wistar rats. PMMs thus effectively enhanced antioxidant and skin protective effect of curcumin and quercetin.

Dapsone-Loaded Mixed Micellar Gel for Treatment OF Acne Vulgaris.

Mixed polymeric micelles are potential nanocarriers for topical drug delivery. Dapsone (DAP) is an antibacterial used as anti-acne agent, but challenged by low water solubility and poor skin permeability. In the present study, DAP-loaded mixed micellar gel was developed comprising Pluronics F-68 and F-127. Micelles were prepared by solvent evaporation method and particle size, ex vivo permeation, drug loading, and entrapment efficiency were determined. Central Composite Design was used to optimize formulation. Independent variables were concentration of Pluronics at three levels while micelle size and drug loading capacities were dependent variables. Droplet size ranged from 400 to 500 nm. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into gel base using HPMC K100M, Sodium CMC, and Carbopol 980 as gelling agents. Gels were evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and subacute dermal toxicity. Compared with solubility of free DAP (0.24+0.056 µg/ml), solubility in mixed micelles was 18.42±3.4 µg/ml in water at room temperature. Order of spreadability of gels was Na CMC < HPMC < Carbopol 980. Carbopol gels displayed thixotropy with index of 3.17. Syneresis for all gels from day 0 to day 30 was found to be in range of 4.2 to 15.6% w/w. Subacute dermal toxicity studies showed no signs of erythema and edema on rat skin until 21 days. These results suggest that mixed micelles can significantly increase solubility and permeability and sustain release of DAP and are suitable carriers for topical DAP delivery in anti-acne therapies.

Pharmacotechnical Evaluation by SeDeM Expert System to Develop Orodispersible Tablets.

Sediment delivery model (SeDeM) system is innovative tool to correlate micromeritic properties of powders with compressibility. It involves computation of indices which facilitate direct compressibility of solids and enable corrective measures through particle engineering. Study had multiple objectives, viz, (i) to enhance solubility of BCS class II, nevirapine using solid dispersions; (ii) SeDeM analyses of excipients and solid dispersions to analyze direct compressibility; and (iii) prepare orodispersible tablets (ODT). Solid dispersions were prepared by solvent evaporation. Superdisintegrants and solid dispersions were analyzed for primary indices of dimension, compressibility, flowability, stability, and disgregability derived from micromeritic properties. Radar diagrams were constructed to provide visual clues to deficient properties for direct compressibility. ODTs were prepared using excipients which passed criteria for direct compressibility and evaluated for tablet properties. Solid dispersions with Eudragit S100 revealed 6 to 10 fold increase in solubility in various dissolution media including biorelevant media in comparison with plain drug. Solubility was found to be pH dependent. SeDeM analyses facilitated identification of superdisintegrants and excipients with unfavorable compressibility. Radar diagrams provided a clear pictorial evidence of lacunae in powder properties. Based on SeDeM results, tablets were formulated by direct compression using crosspovidone, croscarmellose sodium, and mannitol. All batches showed 40% release in first minute in simulated salivary fluid.

Nanosuspension coated multiparticulates for controlled delivery of albendazole.

OBJECTIVE: Improving solubility and bioavailability of albendazole (ALB). SIGNIFICANCE: ALB is a broad-spectrum anthelminthic BCS class II drug with aqueous solubility of solubility of 4.1 mg/l at 25 °C and oral bioavailability of <5%. METHODS: ALB nanosuspensions (NSs) were prepared by evaporative antisolvent precipitation using tocopherol polyethylene glycol succinate (TPGS) and polyvinyl pyrrolidone (PVP) as stabilizers and characterized for particle size, polydispersity index, and zeta potential. 32 factorial design was used to investigate effect of stabilizer concentration and speed of stirring on particle size. Concentration of TPGS was varied from 0.03 to 0.05% w/v and PVP K-30 was constant at 0.04% w/v. Stirring speed range was 1000-3000 rpm. Optimized NS was loaded on Espheres and coated with Eudragit S10& L100 and studied for friability, surface morphology and release kinetics. RESULTS: Factorial experiments revealed pronounced effect of TPGS on particle size. Optimized batch had particle size of 251 ± 7.2 nm and zeta potential -16.2 ± 2.68 mV. Saturation solubility showed increase of 16-fold in water whereas in phosphate buffer increase was fourfold. ALB-NS secondary coated Espheres released 94.3% drug in 10 h whereas ALB-MS (microsuspension) coated Espheres showed 58% release. A 1.3-fold increase in AUC0-10h was evident. Permeation from ALB-NS coated Espheres was 32% in 60 min while for ALB-MS coated Espheres it was 20%. Permeation increase occurred due to presence of TPGS which acts as a permeation enhancer.

Clinical Veterinary Boron Neutron Capture Therapy (BNCT) Studies in Dogs with Head and Neck Cancer: Bridging the Gap between Translational and Clinical Studies.

Translational Boron Neutron Capture Therapy (BNCT) studies performed by our group and clinical BNCT studies worldwide have shown the therapeutic efficacy of BNCT for head and neck cancer. The present BNCT studies in veterinary patients with head and neck cancer were performed to optimize the therapeutic efficacy of BNCT, contribute towards exploring the role of BNCT in veterinary medicine, put in place technical aspects for an upcoming clinical trial of BNCT for head and neck cancer at the RA-6 Nuclear Reactor, and assess the feasibility of employing the existing B2 beam to treat large, deep-seated tumors. Five dogs with head and neck cancer with no other therapeutic option were treated with two applications of BNCT mediated by boronophenyl-alanine (BPA) separated by 3-5 weeks. Two to three portals per BNCT application were used to achieve a potentially therapeutic dose over the tumor without exceeding normal tissue tolerance. Clinical and Computed Tomography results evidenced partial tumor control in all cases, with slight-moderate mucositis, excellent life quality, and prolongation in the survival time estimated at recruitment. These exploratory studies show the potential value of BNCT in veterinary medicine and contribute towards initiating a clinical BNCT trial for head and neck cancer at the RA-6 clinical facility.

Taste Evaluation by Electronic Tongue and Bioavailability Enhancement of Efavirenz.

Self-nanoemulsifying drug delivery systems (SNEDDS) are isotropic and thermodynamically stable mixtures of oil, surfactant, co-surfactant, and drug which emulsify spontaneously on contact with aqueous phase under mild agitation. Efavirenz used for treatment of acquired immune deficiency syndrome, is poorly water soluble and bitter tasting drug resulting in "burning mouth syndrome (BMS)." The objective of this study was to improve solubility and oral bioavailability by formulating liquid-SNEDDS and to mask bitter taste and minimize BMS. Capmul PG8 NF, Cremophor RH40, and Transcutol HP were selected as oil, surfactant, and co-surfactant. Ternary phase diagrams were constructed to evaluate the nanoemulsification region. A 32 factorial design was employed to optimize L-SNEDDS with droplet size and drug release as responses. Optimized batch was subjected to evaluation of taste by human panel method and electronic tongue, cloud point determination, phase separation, in vivo and stability studies. The optimized batch exhibited droplet size of 21.53 nm, polydispersibility index 0.155, and in vitro drug release of 92.26% in 60 min. The in vivo studies revealed 4.5 times enhancement in oral bioavailability. Taste evaluation indicated reduced the intensity and shortened duration of BMS. The formulation was stable at 40°C ± 75% RH after 3 months. Comparison between standard bitter drug and efavirenz in SNEDDS formulation using e-tongue by principal component analysis revealed significant differences in discrimination index, computed by multivariate data analysis. This study demonstrated that L-SNEDDS may be an alternative approach to improve solubility and oral bioavailability and for masking the bitterness of efavirenz.

Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine.

Rilpivrine is BCS class II drug used for treatment of HIV infection. The drug has low aqueous solubility (0.0166 mg/ml) and dissolution rate leading to low bioavailability (32%). Aim of this work was to enhance solubility and dissolution of rilpivirine using beta-cyclodextrin-based nanosponges. These nanosponges are biocompatible nanoporous particles having high loading capacity to form supramolecular inclusion and non-inclusion complexes with hydrophilic and lipophilic drugs for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonyl diimidazole and pyromellitic dianhydride to prepare nanosponges. The nanosponges were loaded with rilpivirine by solvent evaporation method. Binary and ternary complexes of drug with ß-CD, HP-ß-CD, nanosponges, and tocopherol polyethylene glycol succinate were prepared and characterized by phase solubility, saturation solubility in different media, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry was performed. Results obtained from spectral characterization confirmed inclusion complexation. Phase solubility studies indicated stable complex formation. Saturation solubility was found to be 10-13-folds higher with ternary complexes in distilled water and 12-14-fold higher in 0.1 N HCl. Solubility enhancement was evident in biorelevant media. Molecular modeling studies revealed possible mode of entrapment of rilpivirine within ß-CD cavities. A 3-fold increase in dissolution with ternary complexes was observed. Animal studies revealed nearly 2-fold increase in oral bioavailability of rilpivirine. It was inferred that electronic interactions, hydrogen bonding, and van der Waals forces are involved in the supramolecular interactions.

Synthesis and characterization of psyllium seed mucilage grafted with N,N-methylene bisacrylamide.

Psyllium seed polysaccharide was modified to investigate its use as multifunctional pharmaceutical excipient. The objective of this study was isolation of psyllium seed polysaccharide and crosslinking with acrylic acid using N,N-methylene bisacrylamide and its characterization. Acrylic acid was used as monomer and ammonium persulfate as initiator. A full factorial design was employed to optimize the crosslinking. The modified polysaccharide was characterized by FTIR, DSC, PXRD, loss on drying, pH, viscosity, micromeritics properties and swelling studies in 0.1N HCl, 0.5N NaOH, phosphate buffer pH 6.8. It was observed that swelling of crosslinked polysaccharide increased with decreased concentration of monomer and increasing concentration of crosslinker. Greater degree of grafting was observed with increase in crosslinker and monomer concentration. Dispersions of 1% w/v of PPS and APPS show pseudoplastic behavior. No clinical signs of toxicity were evident in repeat dose toxicity studies conducted in rats. Administration of up to 350mg/kg/day of APPS was well tolerated by the animals. Modification of psyllium via graft copolymerization and network formation with the crosslinker, improved the property profile and utility of psyllium polysaccharide. The modified polysaccharide can be used for designing controlled release drug delivery systems due to its swelling ability.

Enhancement of Bioavailability of Non-nucleoside Reverse Transciptase Inhibitor Using Nanosponges.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor which is chronically prescribed for HIV patients. However, it exhibits solubility-limited bioavailability. Aim of this work was to enhance the solubility and dissolution of the Biopharmaceutical Classification System (BCS) class II drug efavirenz, using beta-cyclodextrin-based nanosponges. Nanosponges have high drug loading capacity and are effective for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonates in different ratios to prepare nanosponges. The nanosponges were loaded with efavirenz by solvent evaporation method and the nanosponge with higher drug loading capacity was selected for further studies. Binary and ternary complexes with EFA, NS, and PVP K30 were prepared and characterized by phase solubility, solution state interaction, saturation solubility, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and field emission scanning electron microscopy was performed. Results obtained from spectral characterization confirmed inclusion complexation. Stability constant for ternary complex was found to be 1997 lit/mole, which indicates stable complex formation. The saturation solubility was found to be 17-fold higher with ternary complex in distilled water and about 4-fold in simulated gastric fluid. In vitro dissolution was improved 3 folds with ternary complex. Ternary nanosponge complexes were found to have 2-fold increase in oral bioavailability of efavirenz as compared to plain drug.

Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release.

The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release.

Thermoreversible mucoadhesive in situ nasal gel for treatment of Parkinson's disease.

Parkinson's disease is a degenerative disorder of the central nervous system (CNS). The most obvious symptoms are movement-related such as shaking, rigidity, slowness of movement and difficulty with walking, rigid muscular movements and difficulty in chewing and swallowing especially solid dosage forms. Ropinirole is an anti-Parkinson drug that has low oral bioavailability which is primarily due to first-pass metabolism. The objective of proposed work was to increase bioavailability of ropinirole and avoid patient discomfort by formulating thermoreversible in situ nasal gel. Thermoreversible nasal gels were prepared by cold method using Pluronic F-127 and hydroxy methyl propyl cellulose (HPMC K4M) as gelling agents. Formulations were evaluated for various parameters such as drug content, pH, gelling time, gelling temperature, gel strength, mucoadhesive force, ex vivo diffusion, histological studies and in vivo bioavailability. Formulations displayed gelation at nasal temperature and the gelation time was found to be less than mucociliary clearance time. The nasal residence time was seen to be increased due to mucoadhesion and increased gel strength. The nasal gel formulations showed ex vivo drug release between 56-100% in 5 h. Histological study of sheep nasal mucosa revealed that the gel had a protective effect on the mucosa unlike plain ropinirole which showed evidence of moderate cellular damage. A fivefold increase in bioavailability in brain was observed on nasal administration as compared to IV route. Thermoreversible in situ nasal gel was found to a promising drug delivery for Parkinsonian patients.

Phosphorylation of psyllium seed polysaccharide and its characterization.

Psyllium is widely used as a medicinally active natural polysaccharide for treating conditions like constipation, diarrhea, and irritable bowel syndrome, inflammatory bowel disease, ulcerative colitis and colon cancer. Studies have been performed to characterize and modify the polysaccharide obtained from psyllium seed husk and to evaluate its use as a pharmaceutical excipient, but no studies have been performed to evaluate the properties of the polysaccharide present in psyllium seeds. The present study focuses on phosphorylation of psyllium seed polysaccharide (PPS) using sodium tri-meta phosphate as the cross-linking agent. The modified phosphorylated psyllium seed polysaccharide was then evaluated for physicochemical properties, rheological properties, spectral analysis, thermal analysis, crosslinking density and acute oral toxicity studies. The modified polysaccharide (PhPPS) has a high swelling index due to which it can be categorized as a hydrogel. The percent increase in swelling of PhPPS as compared to PPS was found to be 90.26%. The PPS & PhPPS mucilages of all strengths were found to have shear thinning properties. These findings are suggestive of the potential use of PhPPS as gelling & suspending agent. PhPPS was found to have a mucoadhesive property which was comparable with carbopol.

Nanosponge-based pediatric-controlled release dry suspension of Gabapentin for reconstitution.

CONTEXT: Gabapentin was selected to formulate oral controlled release dry suspension because of short biological half life of 5-7 h and low bioavailability (60%). Gabapentin is a bitter drug so an attempt was made to mask its taste. OBJECTIVE: To formulate and evaluate controlled release dry suspension for reconstitution to increase the bioavailability and to control bitter taste of drug. MATERIALS AND METHODS: Cyclodextrin based nanosponges were synthesized by previously reported melt method. The nanosponge-drug complexes were characterized by FTIR, DSC and PXRD as well as evaluated for taste and saturation solubility. The complexes were coated on Espheres by a suspension layering technique followed by coating with ethyl cellulose and Eudragit RS-100. A dry powder suspension for reconstitution of the microspheres was formulated and evaluated for taste, redispersibility, in vitro dissolution, sedimentation volume, leaching and pharmacokinetics. RESULTS AND DISCUSSION: The complexes showed partial entrapment of drug nanocavities. Significant decrease in solubility (25%) was observed in the complexes than pure drug in different media. The microspheres of nanosponge complexes showed desired controlled release profile for 12 h. Insignificant drug leaching was observed in reconstituted suspension during storage for 7 days at 45 °C/75% RH. Nanosponges effectively masked the taste of Gabapentin and the coating polymers provided controlled release of the drug and enhanced taste masking. The results of in vivo studies showed increase in bioavailability of controlled release suspension by 24.09% as compared to pure drug. CONCLUSION: The dry powder suspension loaded with microspheres of nanosponges complexes can be proposed as a suitable controlled release drug delivery for Gabapentin.

Evaluation of Phosphorylated Psyllium Seed Polysaccharide as a Release Retardant.

The aim of the present study was to modify psyllium seed polysaccharide and evaluate the modified polysaccharide as release retardant in tablets employing ciprofloxacin hydrochloride as model drug. Studies on polysaccharide from psyllium husk has been reported but no work has been reported on characterization and modification of the polysaccharide present in the psyllium (Plantago ovata) seed and the use of the modified polysaccharide as a release retardant in tablets. In this study, the seed gum was modified using sodium trimetaphosphate as crosslinking agent. Sustained release matrix tablets of ciprofloxacin hydrochloride were prepared by wet granulation using various drug-polymer ratios. The polymers investigated were psyllium polysaccharide, phosphorylated psyllium polysaccharide and widely used release retardant hydroxypropyl methylcellulose K100M. The tablets were evaluated for hardness, friability, drug content, swelling profile and in vitro dissolution studies. The matrix tablets containing 1:3 proportion of drug-phosphorylated psyllium polysaccharide was found to have higher hardness as compared to tablets containing 1:1 and 1:2 proportions. The results of swelling behavior in water showed that the tablets containing 1:3 drug:phosphorylated psyllium polysaccharide ratio had swelling comparable to that of tablets containing 1:3 drug:hydroxypropyl methylcellulose ratio. The in vitro dissolution studies shows that the dissolution rate was retarded from 98.41 to 37.6% in 6 h with increase in concentration of phosphorylated psyllium polysaccharide from 100 to 300 mg. Formulations containing psyllium polysaccharide showed complete drug release in 8 h whereas those formulated with phosphorylated psyllium polysaccharide exhibited extended drug release over the 12 h period. Drug release kinetic studies revealed that drug release followed Korsmeyer-Peppas model.

Optimization of Metronidazole Emulgel.

The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole), a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent), and the dependent variables (responses) were a cumulative amount of drug permeated across the dialysis membrane in 24 h (Y 1) and spreadability (Y 2). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses Y 1 and Y 2. The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 2(3) factorial design and could provide an effective treatment against topical infections.

Self-nanoemulsifying drug delivery system of cefpodoxime proxetil containing tocopherol polyethylene glycol succinate.

CONTEXT: Lipid based drug delivery systems have gained prominence in last decade for drugs with dissolution rate limited oral bioavailability. OBJECTIVE: To improve the solubility, permeability and oral bioavailability of cefpodoxime proxetil, ß-lactam antibiotic. It is BCS Class IV drug having solubility 400 µg/mL and 50% oral bioavailability. MATERIALS AND METHODS: Self-nanoemulsifying drug delivery system (SNEDDS) using various surfactant and cosurfactants such as tween 80, tocopheryl polyethylene glycol succinate (TPGS), propylene glycol and Capmul MCM as oil phase were prepared. Ternary phase diagrams were constructed to identify stable microemulsion region. Percent transmittance studies helped to shortlist the surfactant-cosurfactant combination. RESULTS AND DISCUSSION: Tween 80 and TPGS as surfactants and Capmul MCM as oil phase were found to produce stable nanoemulsions. Five formulations of SNEDDS had globule size of 55-60 nm and zeta potential of -4 to -11 mV. Self-emulsification time was between 221 and 370 s, while viscosity was dependent on composition of SNEDDS. Cloud point was above 70°C which indicated the retention of in vivo self-emulsifying properties. Average flux for cefpodoxime proxetil (CP) and SNEDDS was 0.104 and 0.985 µg/cm(2) min. Permeability was 19.72 and 206 for CP and SNEDDS. Liquid SNEDDS spray coated onto micropellets of microcrystalline cellulose (18-20#) were analysed by scanning electron microscope (SEM), self-emulsification and in vitro dissolution. A 5.36-fold increase in area under curve AUC(0-∞) was observed for CP-SNEDDS than plain drug. Minimum inhibitory concentration (MIC) was lower for SNEDDS. Liquid and SNEDDS micropellets were stable under accelerated conditions. CONCLUSION: SNEDDS formulations led to improved oral bioavailability due to enhanced solubilization of selected drug.

Nanocrystallization by evaporative antisolvent technique for solubility and bioavailability enhancement of telmisartan.

Telmisartan is an orally active nonpeptide angiotensin II receptor antagonist used in the management of hypertension. It is a Biopharmaceutics Classification System class II drug having aqueous solubility of 9.9 µg/ml. Telmisartan (TEL) nanocrystals were prepared by evaporative antisolvent precipitation technique using different stabilizers as PVPK30, TPGS, Poloxamer 188, and PEG 6000 in combination or singly. The nanosuspensions were characterized in terms of particle size distribution, zeta potential, and polydispersity index. The suspension containing PVPK30 and TPGS (1:1) showed least average particle size of 82.63 nm and polydispersity index of 0.472. The zeta potential of nanosuspensions ranged between 6.54 and 10.8 mV. An increase of 116.45% was evident in the specific surface area of the freeze-dried product. Contact angle of nanoparticles was also lowered to 27° as compared to 50.8° for TEL. Saturation solubility studies in various media revealed a significant increase in comparison to plain drug. An increase of 3.74× in saturation solubility in FaSSIF and 5.02× in FeSSIF was seen. In vitro dissolution profile of nanosuspension coated on pellets revealed release of 85% in water, 95% in 0.1 N HCl, and 75% in phosphate buffer in 30 min. Nanosuspensions were found to be stable in the presence of univalent and bivalent electrolytes. A tenfold increase in bioavailability was evident. Nanoparticles of telmisartan prepared by bottom-up technique proved to be effective in improving the oral bioavailability as a result of enhanced solubility and dissolution rate.

Social deviance activates the brain's error-monitoring system.

Social psychologists have long noted the tendency for human behavior to conform to social group norms. This study examined whether feedback indicating that participants had deviated from group norms would elicit a neural signal previously shown to be elicited by errors and monetary losses. While electroencephalograms were recorded, participants (N = 30) rated the attractiveness of 120 faces and received feedback giving the purported average rating made by a group of peers. The feedback was manipulated so that group ratings either were the same as a participant's rating or deviated by 1, 2, or 3 points. Feedback indicating deviance from the group norm elicited a feedback-related negativity, a brainwave signal known to be elicited by objective performance errors and losses. The results imply that the brain treats deviance from social norms as an error.

Mechanistic evaluation of the effect of sintering on Compritol 888 ATO matrices.

The present research studied the effect of sintering technique in the development of a controlled release formulation for ketorolac tromethamine. The method consisted of mixing drug and wax powder (Compritol 888 ATO) along with lactose as diluent and talc as lubricant followed by direct compression at room temperature. The compressed fluffy matrices were kept at 80 degrees C for 1, 2, and 3 h for sintering. The sintered tablets were characterized by their physical parameters and in vitro dissolution profile. The sintering time markedly affected the drug release properties of Compritol 888 ATO matrices. It is notable that the release rate of ketorolac tromethamine from matrices was inversely related to the time of sintering. This may be due to the increase in the extent and firmness of sintering which further compacts the mass so that drug release is affected. Contact angle measurement and scanning electron microscopy analysis indicated that heat treatment caused the wax to melt and redistribute. This redistributed wax formed a network-like structure in which the drug along with lactose is entrapped. This particular formed matrix is responsible for retarding the drug release. Fourier transform infrared spectroscopy results did not show any drug-wax interaction due to sintering. Differential scanning calorimetric and powder X-ray diffraction studies ruled out the occurrence of solid solution and polymorphic changes of the drug. Drug release from the wax tablets with or without sintering was best described by the Higuchi equation.

Effect of processing and sintering on controlled release wax matrix tablets of ketorolac tromethamine.

The objective of present study was to evaluate the effect of processing methods and sintering condition on matrix formation and subsequent drug release from wax matrix tablets for controlled release. Ketorolac tromethamine and compritol were processed with appropriate diluent using either dry blending, spray drying, partial melt granulation or melt granulation.The tablets were then sintered at 80 degrees . The sintered tablets were characterized by their physical parameters and in vitro dissolution tests. The micro-morphology and wettability of the tablets was also investigated. It was evident that different processing methods for identical formulation significant impact the release profile of drug. Sintering further retarded drug release and its effect was related to the manufacturing processes. Scanning electron microscopy showed that heat treatment redistributed the wax and formed a film-like structure covering drug and excipient particle. The contact angle of tablets made by dry blending, spray drying and partial melt granulation methods increased after sintering, while that of tablets made by melt granulation remained constant. Drug release from the wax tablets with or without heat treatment was best described by the Higuchi equation. Different processing methods produced different matrix structures that resulted in different drug release rates. Sintering retarded drug release mainly by decreasing the porosity of the matrix. Contact angle measurement and SEM analysis indicated that heat treatment caused the wax to melt, redistribute, coat the drug and diluents and form a network structure. Differential scanning calorimetry studies ruled out the occurrence of solid solution of the drug during sintering condition.