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Chitosan-dextran sulfate nanoparticles of acetazolamide were formulated by using the ionic gelation technique, and evaluated for different attributes like particle size, ζ potential, drug entrapment, particle morphology, in vitro drug release, and in vivo efficacy. Particle size was observed to be changed with the increment of the drug/polymer ratio. Sustained in vitro drug release was exhibited by the particulate formulation that followed the Korsmeyer-Peppas kinetic model. Drug release from nanoparticles was found to occur, as shown by the results, through a combination of dissolution and diffusion. The optimized formulation had a particle size of 172.3 nm and ζ potential of 36.46 mV. The particles had a spherical shape and polydispersity index of 0.257. Decrease in crystallinity of the drug was indicated by powder X-ray diffraction and differential scanning calorimetry studies, in the optimized nanoparticle formulation. Approximately 2.5 times higher transcorneal permeation of drug was observed across the excised goat cornea, in comparison to the aqueous solution of drug, without any corneal damage, during ex vivo transcorneal studies. In vitro mucoadhesion studies showed 91.59% mucoadhesion. The in vivo studies involving ocular hypotensive activity in rabbits revealed significantly higher hypotensive activity with a p-value of

The aim of the present study was to develop and evaluate positively charged nanoparticles of aceclofenac for ocular delivery. The nanoparticles were prepared by the nanoprecipitation method using Eudragit RS 100. The optimized nanoparticles were found to have narrow particle size range (238.9 ± 8 nm) with nearly spherical shape, positive zeta potential (40.3 ± 3.8). Higher entrapment efficiency of aceclofenac (94.53 ± 1.0%) with prolonged in vitro drug release profiles was also observed. Powder X-ray diffraction and differential scanning calorimetry studies indicated decrease in crystallinity of drug within the nanoparticulate polymeric matrix. The formulation was found to have higher permeation as compared to aceclofenac aqueous solution. Nanoparticle formulation was found to be quite stable and well tolerated with no signs of corneal damage. The in vivo studies involving the arachidonic acid-induced ocular inflammation in rabbits showed optimal efficacy of the nanoparticles with significantly higher inhibition of polymorphonuclear leukocytes migration (p < 0.05) and lid closure scores. [ABSTRACT FROM AUTHOR]

Ocular inflammatory diseases, such as uveitis, scleritis, episcleritis and dry eye syndrome are commonly treated with eye drop formulations. In the present study, attempts were made to prepare aceclofenac oil formulations to evaluate its transcorneal permeation and anti-inflammatory effect. Ophthalmic solutions of aceclofenac with or without (0.5% v/v) benzyl alcohol were formulated in different vegetable oils and permeation studies were carried out. Aceclofenac ophthalmic solution in linseed oil containing benzyl alcohol exhibited maximum permeation (4.42% in goat, 4.26% in sheep and 3.94% in buffalo) through corneas under study. The partition characteristics of aceclofenac in linseed oil reinforced the results of permeation studies. The optimized formulation (linseed oil containing benzyl alcohol) showed better stability profile. Linseed oil aceclofenac formulation showed significant inhibitory effect on ocular inflammation induced by arachidonic acid in rabbit eyes (p < .05) and hence it can be considered as a potential approach for treatment of ocular inflammatory conditions. [ABSTRACT FROM PUBLISHER]

Colon-targeted microparticles loaded with a model anti-inflammatory drug were fabricated using especially designed acrylic acid–butyl methacrylate copolymers. Microparticles were prepared by oil-in-oil solvent evaporation method using Span 80 as emulsifier. Microparticles were found to be spherical in shape, hemocompatible and anionic with zeta potential of −27.4 and −29.0 mV. Entrapment of drug in the microparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. However, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed amorphous nature of microparticles due to the dilution effect of amorphous polymer. The microparticles released less than 5% drug at pH 1.2, while more than 90% of the drug load was released at pH 7.4. This suggested the colon targeting nature of the formulations. In experimentally developed colitis in Wistar rats, the microparticle formulation showed significant reduction (p < .05) in the disease activity score (disease symptoms), the colon-to-body weight ratio (tissue edema) and the myeloperoxidase, tumor necrosis factor (TNF)-α and interleukin (IL)-1β activities. [ABSTRACT FROM AUTHOR]

Context: The unique physiological limitations of the eye have been assigned as reason of low bioavailability by conventional drug delivery systems. There is need of such drug carriers, which ensure improved bioavailability as well as patient compliance upon instillation into the eye. Objective: The present investigation deals with development of solid lipid nanoparticles (SLNs) containing celecoxib (CXB) for treatment of ophthalmic inflammations. Materials and methods: The SLNs were formulated by melt-emulsion sonication and low temperature-solidification process and evaluated for particle size, surface morphology, physicochemical properties, percentage drug incorporation efficiency,in vitrodrug release,in vitrotrans-corneal permeation,in vivoefficacy in ocular inflammation, stability study and gamma scintigraphy study to assess the residence of solid lipid nanoparticles over ocular surfaces. Results: The SLNs were spherical and the optimized formulation had particle size of 198.77 ± 7.5 nm, which is quite suitable for ocular applications. The maximum entrapment efficiency of 92.46 ± 0.07% was achieved for formulation SLN 20. The permeation across the cornea was also significantly better than aqueous suspension (8.21 ± 0.67 versus 4.61 ± 0.71) atp < 0.05. Discussion and conclusion: The SLN formulations demonstrated improved performance of entrapped CXB while mitigating the key parameters of ocular inflammation in rabbits. The particulate formulations have exhibited prolonged retention over ocular surfaces as evident from results of gamma scintigraphy using99mTc labeled SLNs. [ABSTRACT FROM AUTHOR]

Hydrophilic monomer methacrylic acid was copolymerized with hydrophobic monomer butylmethacrylate in different molar ratio, using AIBNfree radical initiator. Successful polymerization was confirmed by FTIR and1H NMR, while DSC and XRD revealed the amorphous nature of the polymers. Copolymers were highly hemocompatible. The polymers showed pH-dependent swelling and erosion which increased with increase in pH. As the amount of methacrylic acid increased, the swelling and erosion also increased. Polymers were used for the microencapsulation of a model anti-inflammatory drug, aceclofenac by an oil-in-oil solvent evaporation method. Microparticles were characterized using FTIR, XRD, DSC, and SEM analysis. The negatively charged particles were almost spherical in shape. The drug release was best explained by zero-order kinetics with anomalous release mechanism. Less than 1% of drug was released at pH 1.2 while the bulk of the drug load was released at pH 6.8 or above, confirming the colon-targeting nature. The microparticles showed significant lowering in myeloperoxidase activity in trinitrobenzene sulfonic acid-induced colitis rat model. There was a significant lowering in the severity of disease symptoms and colon-to-body weight ratio. The histopathological studies also confirmed successful treatment with microparticle formulation. [ABSTRACT FROM PUBLISHER]

In the current study, polylactide-co-glycolide (PLGA) nanoparticles entrapping both clozapine (CLZ) and risperidone (RIS) were formulated by spray-drying using Buchi Nano Spray Dryer B-90 (Flawil, Switzerland). Parameters such as inlet temperature, spray mesh diameter, sample flow rate, spray rate and applied pressure were optimized to produce nanoparticles having desired release profile using both low- and high-molecular weight PLGA polymer. Smallest size nanoparticle of size around 248 nm could be prepared using a 4.0 μm mesh diameter with low-molecular weight polymer. The load of CLZ and RIS was 126.3 and 58.2 μg/mg of polymer particles, respectively. Entrapment efficiency of drugs in PLGA nanoparticles was 94.74% for CLZ and 93.12% for RIS. Both the drugs released continuously from the nanoparticle formulations. PLGA nanoparticles formulated using low-molecular weight polymer released around 80% of the entrapped drug over 10 days of time. Nature of drug inside polymer particles was amorphous, and there was no chemical interaction of CLZ and RIS with polymer. Polymeric nanoparticles were found to be non-toxic in nature using PC12 cell line. This nanospray drying process proved to be suitable for developing polymeric nanoformulation delivering dual drugs for the treatment of Schizophrenia. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the feasibility of entrapping water-insoluble drug itraconazole into solid lipid nanoparticles (SLNs) for topical ocular delivery. The drug-loaded SLNs were prepared from stearic acid and palmitic acid using different concentrations of polyvinyl alcohol employed as emulsifier. SLNs were prepared by the melt-emulsion sonication and low temperature-solidification method and characterized for particle size, zeta potential, drug loading and drug entrapment efficiency. The mean particle size of SLNs prepared with stearic acid ranged from 139 to 199 nm, while the SLNs prepared with palmitic acid had particle size in the range of 126-160 nm. The SLNs were spherical in shape. Stearic acid-SLNs showed higher entrapment of drug compared with palmitic acid-SLNs. Differential scanning calorimetry (DSC) and X-ray diffraction measurements showed decrease in crystallinity of drug in the SLN formulations. The modified Franz-diffusion cell and freshly excised goat corneas were used to test drug corneal permeability. Permeation of itraconazole from stearic acid-SLNs was higher than that obtained with palmitic acid-SLNs. The SLNs showed clear zone of inhibition against Aspergillus flavus indicating antimicrobial efficacy of formulations. [ABSTRACT FROM AUTHOR]

Attempts have been made to optimize immobilization parameters, catalytic property, and stability of immobilized α-amylase in agar. The work compares natural entrapment efficiency of agar with the ionotropically cross-linked agar hydrogel, with the advantage of easy scale-up and cost and time effectiveness. Beads prepared with 3% (w/v) agar and 75 mM calcium chloride and hardened for 20 minutes were selected for further studies on the basis of entrapment efficiency (80%) and physical stability. Following entrapment, pH and temperature optima of enzyme were shifted from 6 to 6.5 and 50 to 55°C, respectively. Michaelis constant (Km) for both free and entrapped enzymes remained the same (0.83%) suggesting no change in substrate affinity. However, Vmax of entrapped enzyme decreased ~37.5-fold. The midpoint of thermal inactivation for entrapped enzyme increased by 8 ± 1°C implying its higher thermal stability. The entrapped enzyme in calcium agar bead had an Ea value of 27.49 kcal/mol compared to 17.6 kcal/mol for free enzyme indicating increased stability on entrapment. Half-life of enzyme increased ~2.2 times after entrapment in calcium agar at 60°C indicating stabilization of enzyme. The reusability of beads was size dependent. Beads with diameter <710 µm were stable and could be reused for 6 cycles with ~22% loss in activity. [ABSTRACT FROM AUTHOR]

The binary mixture tablets of papain and microcrystalline cellulose (MCC), dicalcium phosphate dihydrate (DCP), carrageenan, tragacanth, and agar were prepared by direct compression. Carrageenan, tragacanth, and agar provided maximum protection to enzyme activity compared to MCC and DCP. However, stability studies indicated highest loss of enzyme activity with carrageenan, tragacanth, and agar. Therefore, compression behaviour of different binary mixtures of papain with MCC at different compaction pressures, that is, 40-280 MPa, was studied according to Heckel equation. The compressibility studies of binary mixtures indicated brittle behavior of papain. The application of percolation theory on the relationship between critical density as a function of enzyme activity and mixture composition revealed the presence of percolation threshold for binary mixture. Papain-MCC mixture composition showed significant percolation threshold at 18.48% (w/w) papain loading. Microcrystalline cellulose provided higher protection during stability study. However, higher concentrations of microcrystalline cellulose, probably as dominant particles, do not protect the enzyme with their plastic deformation. Below the percolation threshold, that is, 18.48% (w/w) papain amount in mixture with plastic excipient, activity loss increases strongly because of higher shearing forces during compaction due to system dominance of plastic particles. This mixture range should therefore be avoided to get robust formulation of papain. [ABSTRACT FROM AUTHOR]

The purpose of this research was to evaluate the effect the formulation factors on in vitro permeation of voriconazole through freshly isolated goat and sheep corneas. An increase in the pH of the drops from 4.0 to 8.0 resulted in significant (P < 0.05) increase drug permeation. Raising concentration of the drops from 0.05% to 0.2% (w/v) significantly, (P < 0.05) increased drug permeation, but decreased the percent permeation. Corneal transport of voriconazole is both pH and concentration dependent. Eye drops containing disodium edetate (ethylenediaminetetraacetic acid) alone or combination with benzalkonium chloride showed significantly (P < 0.05) higher permeation as compared with control formulation. Addition of beta-cyclodextrin to the formulation enhanced corneal permeation of voriconazole. Compared with control formulation, voriconazole 0.2% (w/v) drop containing viscosity modifier produced significant (P < 0.05) decrease in permeation. Most of the formulations showed higher zone of inhibition against Candida albicans. [ABSTRACT FROM AUTHOR]

Enteric submicron particles (SPs) formulations of α-amylase were prepared by w/o/w emulsion solvent evaporation using hydroxypropyl methylcellulose phthalate (HPMCP) and Eudragit L 100, to avoid gastric inactivation of α-amylase. Smaller internal and external aqueous phase volume provided maximum encapsulation efficiency (71.92-73.40%), least particle size (546.4-595.4 nm) and 23-26% loss of enzyme activity. Release studies in 0.1 N HCl confirmed the gastro-resistance of formulations. The anionic SPs aggregated in 0.1 N HCl (i.e. gastric pH 1.2), due to protonation of carboxylic groups of enteric polymer. The aggregates being < 500 µm size would not impede gastric emptying. However, at pH >5.0 (duodenal pH), SPs showed de-aggregation due to restoration of surface charge. HPMCP and Eudragit L 100 SPs facilitated almost complete release of α-amylase within 30 min at pH 6.0 and 6.8, respectively, following Higuchi kinetics. PXRD and DSC indicated amorphous character and scanning electron microscope showed spherical shape of SPs. In simulated gastro-intestinal pH condition, HPMCP and Eudragit L 100 SPs showed good digestion of cooked rice and could serve as potential carrier for oral enzyme delivery. Stability studies indicated the formulations as quite stable to ensure 2 years shelf life at room temperature. [ABSTRACT FROM AUTHOR]

The intake of omega-3 unsaturated fatty acids has a beneficial effect on insulin sensitivity in rats and in subjects with type 2 diabetes. It has been reported that these omega-3 fatty acids are useful in the treatment of hypertriglyceridemia and in the enhancement of high-density lipoprotein (HDL)-cholesterol levels in diabetic patients. The present study was therefore aimed to evaluate the antioxidant, antihyperglycemic and antihyperlipidemic effect of L. usitatissimum fixed oil. The antioxidant activity was evaluated in vitro using 1,1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide (H2O2) assay. The oil exhibited significant in vitro antioxidant activity in the DPPH and H2O2 assay. The oil (1, 2, 3 mL/kg) was further investigated against streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in albino rats, subjected to 3 weeks of treatment. The oil manifested decrease in blood glucose and glycated hemoglobin levels at higher dose and significant dose dependent negating action on antioxidant enzymes in the heart, liver and kidney tissues. The oil also normalized the various hematological parameters and electrolyte levels in the STZ treated rats. Treatment with oil significantly increased the level of serum HDL and decreased the levels of total cholesterol, triglycerides, and low-density lipoprotein-cholesterol in STZ-diabetic rats in comparison to normal control. The antioxidant, antihyperglycemic and antihyperlipidemic activity of the oil could be attributed to the presence of linolenic acid (ALA, 18:3 n-3) and its metabolic products, eicosapentanoic acid (EPA, 20:5 n-3) and docosahexanoic acid (DHA, 22:6 n-3). [ABSTRACT FROM AUTHOR]

In this study, diclofenac-loaded Eudragit S100-based nanosuspension was prepared by nanoprecipitation method and characterised for particle size, morphology, in vitro release, and for its in vivo ocular anti-inflammatory activity. The diclofenac-loaded Eudragit S100 nanosuspension was found to have a particle size of 172 nm, polydispersibility index of 0.14 and zeta potential of −23.7 ± 6.07 mV, indicating that the nanosuspension is fairly stable. The nanosuspended particles were found to be spherical in shape. The nanosuspension was found to provide a sustained in vitro release, following the Higuchi square-root release kinetics. The results indicated that the nanosuspension released the drug by combination of dissolution and diffusion. The in vivo evaluation of nanosuspension in PGE2-induced ocular inflammation in rabbit model revealed a significantly ( p < 0.05) higher inhibition of PGE2-induced polymorphonuclear leukocytes migration and lid-closure scores as compared with the aqueous solution of diclofenac. [ABSTRACT FROM AUTHOR]

The binary mixture tablets of papain and microcrystalline cellulose (MCC), dicalcium phosphate dihydrate (DCP), carrageenan, tragacanth, and agar were prepared by direct compression. Carrageenan, tragacanth, and agar provided maximum protection to enzyme activity compared to MCC and DCP. However, stability studies indicated highest loss of enzyme activity with carrageenan, tragacanth, and agar. Therefore, compression behaviour of different binary mixtures of papain with MCC at different compaction pressures, that is, 40-280 MPa, was studied according to Heckel equation. The compressibility studies of binary mixtures indicated brittle behavior of papain. The application of percolation theory on the relationship between critical density as a function of enzyme activity and mixture composition revealed the presence of percolation threshold for binary mixture. Papain-MCC mixture composition showed significant percolation threshold at 18.48% (w/w) papain loading. Microcrystalline cellulose provided higher protection during stability study. However, higher concentrations of microcrystalline cellulose, probably as dominant particles, do not protect the enzyme with their plastic deformation. Below the percolation threshold, that is, 18.48% (w/w) papain amount in mixture with plastic excipient, activity loss increases strongly because of higher shearing forces during compaction due to system dominance of plastic particles. This mixture range should therefore be avoided to get robust formulation of papain.

Attempts have been made to optimize immobilization parameters, catalytic property, and stability of immobilized α-amylase in agar. The work compares natural entrapment efficiency of agar with the ionotropically cross-linked agar hydrogel, with the advantage of easy scale-up and cost and time effectiveness. Beads prepared with 3% (w/v) agar and 75 mM calcium chloride and hardened for 20 minutes were selected for further studies on the basis of entrapment efficiency (80%) and physical stability. Following entrapment, pH and temperature optima of enzyme were shifted from 6 to 6.5 and 50 to 55°C, respectively. Michaelis constant (K m ) for both free and entrapped enzymes remained the same (0.83%) suggesting no change in substrate affinity. However, V max⁡ of entrapped enzyme decreased ~37.5-fold. The midpoint of thermal inactivation for entrapped enzyme increased by 8 ± 1°C implying its higher thermal stability. The entrapped enzyme in calcium agar bead had an Ea value of 27.49 kcal/mol compared to 17.6 kcal/mol for free enzyme indicating increased stability on entrapment. Half-life of enzyme increased ~2.2 times after entrapment in calcium agar at 60°C indicating stabilization of enzyme. The reusability of beads was size dependent. Beads with diameter <710 μm were stable and could be reused for 6 cycles with ~22% loss in activity.

Introduction: Topical fluoroquinolones are used in ophthalmology to treat ocular infections. They are bactericidal and inhibit bacterial DNA replication by inhibiting DNA gyrase and topoisomerase. Fluoroquinolones possess two ionizable groups: a carboxylic group (pKa1 = 5.5 - 6.34) and a heterocyclic group (pKa2 = 7.6 - 9.3), in the nucleus, which acquire charge at pH above and below the isoelectric point (pI = 6.75 - 7.78). At isoelectric point, fluoroquinolones remain unionized and show enhanced corneal penetration but exhibit reduced aqueous solubility and the drug may precipitate from aqueous solution. Aqueous ophthalmic solutions of fluoroquinolones are obtained by using hydrochloride or mesylate salt which is acidic and irritating to the eyes. Hence, pH of the solution is kept between 5 and 7 to ensure aqueous solubility and minimum ocular irritation., Areas Covered: This review gives an overview of various physicochemical and formulation factors affecting the ocular delivery of fluoroquinolones and strategies for getting higher ocular bioavailability for ocular delivery of fluoroquinolones. These strategies could be employed to improve efficacy of fluoroquinolones in eye preparation., Expert Opinion: Broad-spectrum antibacterials, such as the ophthalmic fluoroquinolones, are powerful weapons for treating and preventing potentially sight-threatening infections. The fourth-generation fluoroquinolones have quickly assumed an outstanding place in the ophthalmic applications. Especially valuable for their broad-spectrum coverage against Gram-positive and Gram-negative organisms, these agents have become the anti-infective of preference for many ophthalmologists. Moxifloxacin seems to be a promising powerful molecule among all fluoroquinolones for treatment of bacterial infections.

The present investigation summarizes the effect of Linum usitatissimum fixed oil against different phases of acute inflammatory reaction, namely, protein exudation, peritoneal capillary permeability, and leukocyte migration. The fixed oil exhibited dose-dependent inhibition of protein exudation vascular permeability, comparable to standard aspirin. The oil also inhibited the leukocyte migration in pleural exudates in a dose-dependent manner. Production of less vasodilatory (PGE3) and chemotactic (LTB5) eicosanoids through EPA (derived from linolenic acid) metabolism could account for the above observations.

Introduction: Eudragit is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives., Areas Covered: In this review, the physicochemical characteristics and applications of different grades of Eudragit in colon-specific/enteric-coated/sustained release drug delivery and taste masking have been addressed., Expert Opinion: Eudragits are amorphous polymers having glass transition temperatures between 9 to > 150(o)C. Eudragits are non-biodegradable, nonabsorbable, and nontoxic. Anionic Eudragit L dissolves at pH > 6 and is used for enteric coating, while Eudragit S, soluble at pH > 7 is used for colon targeting. Studies in human volunteers have confirmed that pH drops from 7.0 at terminal ileum to 6.0 at ascending colon, and Eudragit S based systems sometimes fail to release the drug. To overcome the shortcoming, combination of Eudragit S and Eudragit L which ensures drug release at pH < 7 has been advocated. Eudragit RL and RS, having quaternary ammonium groups, are water insoluble, but swellable/permeable polymers which are suitable for the sustained release film coating applications. Cationic Eudragit E, insoluble at pH ≥ 5, can prevent drug release in saliva and finds application in taste masking.

The objective of the present investigation was to prepare and evaluate ocular inserts of moxifloxacin. An ocular insert was made from an aqueous dispersion of moxifloxacin, sodium alginate, polyvinyl alcohol, and dibutyl phthalate by the film casting method. The ocular insert (5.5 mm diameter) was cross-linked by CaCl2 and was coated with Eudragit S-100, RL-100, RS-100, E-100 or L-100. The in vitro drug drainage/permeation studies were carried out using an all-glass modified Franz diffusion cell. The drug concentration and mucoadhesion time of the ocular insert were found satisfactory. Cross-linking and coating with polymers extended the drainage from inserts. The cross-linked ocular insert coated with Eudragit RL-100 showed maximum drug permeation compared to other formulations.

The fixed oil of L. usitatissimum (flaxseed/linseed) inhibited PGE2-, leukotriene-, histamine- and bradykinin-induced inflammation. The oil also inhibited arachidonic acid-induced inflammation, suggesting its capacity to inhibit both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism. In tail immersion model, the oil raised the pain threshold to a lesser extent than morphine but showed excellent peripherally acting, analgesic activity comparable to aspirin, against acetic acid-induced writhing in mouse. In typhoid paratyphoid A/B vaccine-induced pyrexia, the oil showed antipyretic activity comparable to aspirin. The oil contains 57.38% alpha-linolenic acid. Dual inhibition of arachidonic acid metabolism, antihistaminic and antibradykinin activities of the oil could account for the biological activity and the active principle could be alpha-linolenic acid an omega-3 (18:3, n-3) fatty acid.

Background: Particulate systems have received increasing attention for oral delivery of biomolecules. The objective of the present study was to prepare submicron particulate formulations of papain for pH-dependent site-specific release using pH-sensitive polymers., Methods: Enteric submicron particle formulations of papain were prepared by w/o/w emulsion solvent evaporation using hydroxypropyl methylcellulose phthalate (HPMCP), Eudragit L100, and Eudragit S100, to avoid gastric inactivation of papain., Results: Smaller internal and external aqueous phase volumes provided maximum encapsulation efficiency (75.58%-82.35%), the smallest particle size (665.6-692.4 nm), and 25%-30% loss of enzyme activity. Release studies in 0.1 N HCl confirmed the gastroresistance of the formulations. The anionic submicron particles aggregated in 0.1 N HCl (ie, gastric pH 1.2) due to protonation of carboxylic groups in the enteric polymer. Aggregates < 500 μm size would not impede gastric emptying. However, at pH > 5.0 (duodenal pH), the submicron particles showed deaggregation due to restoration of surface charge. HPMCP submicron particles facilitated almost complete release of papain within 30 minutes at pH 6.0, while Eudragit L100 and Eudragit S100 particles released 88.82% and 53.00% of papain at pH 6.8 and pH 7.4, respectively, according to the Korsmeyer-Peppas equation. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorescence spectroscopy confirmed that the structural integrity of the enzyme was maintained during encapsulation. Fourier transform infrared spectroscopy revealed entrapment of the enzyme, with powder x-ray diffraction and differential scanning calorimetry indicating an amorphous character, and scanning electron microscopy showing that the submicron particles had a spherical shape., Conclusion: In simulated gastrointestinal pH conditions, the HPMCP, Eudragit L100, and Eudragit S100 submicron particles showed good digestion of paneer and milk protein, and could serve as potential carriers for oral enzyme delivery. Stability studies indicated that formulations with approximately 6% overage would ensure a two-year shelf-life at room temperature.

Enteric microspheres formulations of papain were prepared by w/o/w emulsion solvent evaporation using hydroxypropyl methylcellulose phthalate (HPMCP), Eudragit L 100 and Eudragit S 100, to avoid gastric inactivation of papain. Smaller internal and external aqueous phase volume provided maximum encapsulation efficiency (74.49-79.76%), least particle size (52.4-60.2 µm) and 21-26% loss of enzyme activity. Release studies in 0.1 N HCl confirmed the gastro-resistance of formulations. The anionic microspheres, zeta potential between -18.21 and -20.06 mV, aggregated in 0.1 N HCl (i.e., gastric pH 1.2), due to protonation of carboxylic groups of enteric polymer and loss of surface charge with subsequent change in zeta potential. The aggregates being <500 µm size would not impede gastric emptying. However, at pH>5.0 (duodenal pH) the microspheres showed de-aggregation due to restoration of surface charge. HPMCP and Eudragit L 100 microspheres facilitated almost complete release of papain within an hour at pH 6.0 and 6.8, respectively while Eudragit S 100 microspheres released 84.56% papain at pH 7.4, following Higuchi kinetics. FTIR spectroscopy revealed entrapment of enzyme; PXRD & DSC indicated amorphous character and SEM showed spherical shape of microspheres. In simulated gastro-intestinal pH condition, HPMCP, Eudragit L 100 and Eudragit S 100 microspheres showed good digestion of paneer and milk protein. Thus, enteric microspheres formulations could serve as potential carrier for oral enzyme delivery. Stability studies indicated the formulations with around 5% overage would ensure 2 years shelf life at room temperature.

The aim of the present study was to prepare valdecoxib, a cyclo-oxygenase-2 enzyme inhibitor, as a loaded multiparticulate system to achieve site-specific drug delivery to colorectal tumors. Film coating was done with the pH-sensitive polymer Eudragit S100 and sodium alginate was used as mucoadhesive polymer in the core. The microspheres were characterized by X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy and were evaluated for particle size, drug load, in vitro drug release, release kinetics, accelerated stability, and extent of mucoadhesion. The coated microspheres released the drug at pH 7.4, the putative parameter for colonic delivery. When applied to the mucosal surface of freshly excised goat colon, microspheres pretreated with phosphate buffer pH 7.4 for 30 minutes showed mucoadhesion. To ascertain the effect of valdecoxib on the viability of Caco-2 cells, the 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide) test was conducted using both valdecoxib and coated microspheres. In both cases, the percentage of dehydrogenase activity indicated a lack of toxicity against Caco-2 cells in the tested concentration range. Drug transport studies of the drug as well as the coated microspheres in buffers of pH 6 and 7.4 across Caco-2 cell monolayers were conducted. The microspheres were found to exhibit slower and delayed drug release and lower intracellular concentration of valdecoxib.

A study was undertaken to determine the longevity of active muscarinic receptors on abattoir-sourced isolated ileum preparations from Gallus gallus domesticus, with a view to using the tissue as an experimental tool for functional response assays in laboratory experiments. A concentration-response curve for acetylcholine (1-256 μM) was plotted, in the presence and absence of 1, 3 and 6 nM atropine. In a second experiment, unknown concentrations of acetylcholine samples were determined by using an interpolation method. In this experiment, four sample concentrations were used and the calculated values were found to be almost equal to the actual values. Finally, an experiment was carried out to elucidate the effects of post-sacrifice time on the contractile response of the tissue. The results showed that the tissue maintained considerable contractile response at the 6-hour post-sacrifice time-point. Competitive antagonistic activity was observed between acetylcholine and atropine on the chicken ileum, and the pA2 value was calculated to be 9.21 by using an Arunlakshana-Schild plot. The results suggest that isolated ileum preparations of Gallus gallus domesticus, obtained from a meat abattoir, can be used as a basic experimental tool for bioassays in routine laboratory experiments. However, its potential as a research tool still needs to be confirmed., (© 2010 FRAME.)

Pulmonary insulin delivery is steadily emerging as a promising solution for the treatment of diabetes mellitus. The large as well as thin absorptive area of the lungs has not been explored until now for the treatment of systemic disease like diabetes. With an understanding of the lung anatomy and physiology and the transport mechanism of insulin through lungs, diabetic treatment through the pulmonary route may well become the reality of the 21(st) century. Though the transport of insulin through the lungs itself appears quite encouraging, potential problems concerning the formulation of a peptide like insulin in the form of an aerosol seem to be the most challenging. Stability aspects, stringent control of Mass Median Aerodynamic Diameter, antigenicity, insulin losses due to the device and impaction, sedimentation and diffusion in the nonabsorptive areas of the airway system (especially in the oropharynx) emerge as major concerns. This is in addition to the problems of lack of reproducibility of dose delivery by an inhaler where individual variations due to inspiratory differences and method of use of device come into play. Lung diseases and smoking may alter lung mechanisms and dose alterations are to be studied in such cases. Though almost equally effective, if not more, than the subcutaneous insulin route, even with proved short-term efficacy, insulin delivery through lungs is a potential but not a wholly proven means for blood glucose control.

Seeds of Ocimum sanctum L. (Labiatae; popularly known as 'Tulsi' in Hindi and 'Holy Basil' in English) contain a pale yellow colored fixed oil. The oil possesses antiinflammatory activity due to dual inhibition of arachidonate metabolism supplemented by antihistaminic activity. The antiinflammatory activity is not dependent on the pituitary adrenal axis. The oil possesses antipyretic activity due to prostaglandin inhibition and peripherally acting analgesic activity. The oil has been found to be effective against formaldehyde or adjuvant induced arthritis and turpentine oil induced joint edema in animals. Lipoxygenase inhibitory, histamine antagonistic and antisecretory activities of the oil contribute towards antiulcer activity. The oil can inhibit enhancement of vascular capillary permeability and leucocyte migration following inflammatory stimulus. The LD50 of the oil is 42.5 ml/kg and long-term use of oil at 3 ml/kg dose does not produce any untoward effects in rats. The oil contains a-linolenic acid, an omega-3 fatty acid, which on metabolism produces eicosapentaenoic acid and the same appears to be responsible for the biological activity. The oil has hypotensive, anticoagulant and immunomodulatory activities. Antioxidant property of the oil renders metabolic inhibition, chemoprevention and hypolipidaemic activity. Presence of linolenic acid in the oil imparts antibacterial activity against Staphylococcus aureus. The oil alone or in combination with cloxacillin, a beta-lactamase resistant penicillin, has been found to be beneficial in bovine mastitis, an inflammatory disorder resulting from staphylococcal infection. Existence of anti-inflammatory, analgesic and antibacterial activities in single entity i.e. fixed oil appears to be unique.