Extraction of Saffron Crocin as a Natural Pharmaceutical Source with Solidifi...IjcmsdrJournal
In this research with crystallization method, saffron Crocin was extracted. Ethanol 80% and acetone was chosen as the best extraction solvent. Crystallization and purification process was performed in two steps in zero and -5c° degree. In first step, saffron Crocin was extracted with ethanol and after keeping in -5c° for 23 days obtained Crystals were separated. Obtained Crocin crystals from the first step had low purity and thepure crystals were yielded during the second crystallization. Extraction and purity of Crocin crystals were studied by UV-visible spectrophotometry and Fourier transform spectrometry and HPLC analysis compared to Crocin Sigma-Aldrich. Results show that the extraction intensity and purity of the obtained Crocins were significantly higher than Sigma Aldrich crocin. The results of this research showed that purchased Crocin according to the chromatograms is not pure and some unknown impurity was seen. Besides, Chromatogram spectra's shows that obtained Crocin crystals were in higher purity than purchased one.
An Experimental Investigation on Treatment of Tannery Effluent Using Azadirac...IJEAB
A preliminary investigation was carried out for the feasibile use of Azadirachta indica leafs powder as a natural coagulant to the treatment of tannery effluent. In this paper, Azadirachta indica leafs powder of 1, 2, 3 and 4mg/L dosages were used. Floc formation in coagulation process had been studied in the laboratory scale to determine the optimum dosage of natural coagulant. The above dosages were used in pre-treated tannery effluent with coagulants were considered to evaluate the percentage removal efficiency on the major pollutants of concern in in tannery effluent such as turbidity, TSS, TDS, COD and BOD. From the observed results, dosage of 3 mg/L gives better removal efficiencies with respect to turbidity, TSS, TDS, COD and BOD and appears to be suitable for tannery effluent treatment, when compared with other dosages.
Extraction of Saffron Crocin as a Natural Pharmaceutical Source with Solidifi...IjcmsdrJournal
In this research with crystallization method, saffron Crocin was extracted. Ethanol 80% and acetone was chosen as the best extraction solvent. Crystallization and purification process was performed in two steps in zero and -5c° degree. In first step, saffron Crocin was extracted with ethanol and after keeping in -5c° for 23 days obtained Crystals were separated. Obtained Crocin crystals from the first step had low purity and thepure crystals were yielded during the second crystallization. Extraction and purity of Crocin crystals were studied by UV-visible spectrophotometry and Fourier transform spectrometry and HPLC analysis compared to Crocin Sigma-Aldrich. Results show that the extraction intensity and purity of the obtained Crocins were significantly higher than Sigma Aldrich crocin. The results of this research showed that purchased Crocin according to the chromatograms is not pure and some unknown impurity was seen. Besides, Chromatogram spectra's shows that obtained Crocin crystals were in higher purity than purchased one.
An Experimental Investigation on Treatment of Tannery Effluent Using Azadirac...IJEAB
A preliminary investigation was carried out for the feasibile use of Azadirachta indica leafs powder as a natural coagulant to the treatment of tannery effluent. In this paper, Azadirachta indica leafs powder of 1, 2, 3 and 4mg/L dosages were used. Floc formation in coagulation process had been studied in the laboratory scale to determine the optimum dosage of natural coagulant. The above dosages were used in pre-treated tannery effluent with coagulants were considered to evaluate the percentage removal efficiency on the major pollutants of concern in in tannery effluent such as turbidity, TSS, TDS, COD and BOD. From the observed results, dosage of 3 mg/L gives better removal efficiencies with respect to turbidity, TSS, TDS, COD and BOD and appears to be suitable for tannery effluent treatment, when compared with other dosages.
In the present study, a gastro retentive micro particulate system was formulated with different Polymers by using
solvent evaporation technique. A series of 8 formulations was prepared based on 23 Design of experiments. The
formulated microspheres were evaluated flow characteristics, Practical yield (up to 80 %) and Encapsulation
efficiency (up to 94%). Scanning electron Microscopy confirmed their porous and spherical structure and the
particles were of the Size range of (65-525 μm). The release of drug at 1 hour and 8 hours’ time points were
taken as the measurable parameters for running the DOE experiments. According to design space Hollow
Microspheres formulated with Drug in the range of 50 to 70 mg/unit, Ethyl cellulose 7 cps in the range of 145 to
150 mg/unit and HPMC 5 cps in the range of 0.4 to 2 mg/unit were observed to have the best floating
characteristics and in vitro dissolution profile as per the preset target product profile. Stability studies showed no
significant change in the drug content in the formulations at 3 months accelerated condition. In this study
concluded that a micro particulate floating dosage form of an anti-infective drug can be successfully designed to
give controlled release and improved oral bioavailability.
KEYWORDS
Gastro retentive system, Ciprofloxacin Hcl, Ethyl Cellulose 7 cps, HPMC 5cps, Hollow microspheres.
Separation of Water to Concentrate Aloe Vera Juice:IJERA Editor
Aloe Vera is a succulent plant and is found in different arid areas. Due to its healing effect and soothing
properties it is being used in herbal medicines for years and its importance has grown due to use in cosmetic
products. It contains more than thirty active ingredients, which are utilized in cosmetic and pharmaceutical
industry. It also contains 98% water. To remove water from those active ingredient Reverse osmosis is used in
order not to thermally damage the active ingredients present in the juice. A reverse osmosis is a separation
technique which utilizes difference in pressure to segregate water from plant without damaging the active
ingredients present in the plant. This research is dedicated to evaluate the parameter for separation of water from
aloe Vera so that aloe Vera can be obtained in a form which can be utilized for different purposes such as
cosmetics and medicine. Osmosis technique is preferred over other conventional technique for the separation
purpose because it is not operated at high temperature, which will not damage the aloe Vera juice quality. Next
step in this research is the preserving, drying and analysis of this juice so that this product can be utilized in
versatile way.
This presentation gives brief idea about types of inhalation devices, types of DPIs devices, QbD elements, bioequivalence requirement in USA and EU, and marketed DPI products.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the quality control tests of parenteral as referred in the pharmacopoeia.
Thank you for reading. Hope it was of help to you.
UIPS,PU team
Polymeric Nanoparticles of Rifampicin were prepared by emulsion solvent evaporation technique using poly methyl methacrylate as polymer matrix and Poly vinyl alcohol as surfactant. Drug entrapped free flowing nanoparticles of Rifampicin were obtained after optimization using 32 factorial design and characterized for entrapment efficiency, particle size distribution, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and in vitro and stability studies. The PMMA nanoparticles had a small size (213 ± 0.72 nm), uniform size distribution. The effects of dependent variables drug-polymer ratio and surfactant concentration on particle size and encapsulation efficiency were studied. The drug and polymer were not interacting with each other. SEM studies revealed the spherical shape of nanoparticles and in vitro release studies showed sustained drug release. RIF-polymeric nanoparticles drug delivery system proved to be promising for anti-tubercular therapy.
Synthesis, Characterization and invitro Anti- inflammatory activity of 1, 3, ...SriramNagarajan19
Oxadiazole derivatives have played a vital part in the development of heterocyclic compounds. In this present work, a series of 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-thione derivatives (1-10) have been synthesized by Mannich reaction. The reaction progress of the synthesized compounds was checked by TLC. The structures of the newly synthesized compounds were confirmed by IR and 1H NMR spectral data. The in-vitro anti-inflammatory activity of 1, 3, 4-oxadiazole compounds (1-10) was assessed by HRBC Membrane Stabilization Method. Among the newly synthesized 1,3,4-oxadiazole derivatives, compounds OFP, OAP, OBNP, OPBNP, ORP, OUP, OPClBP, OFD, OAD and OBND possessed highly significant anti-inflammatory activity at a dose of 1000µg/ml when compared with standard, Diclofenac potassium.
Development of Gastroretentive Floating Tablets Quetiapine Fumarateijtsrd
The idea of the study is to prepare and characterize a sustain release floating tablets of Quetiapine Fumarate for Schizophrenia. Materials which are used in making of effervescent Tablets are hydroxy methylcellulose HPMC. For the buoyancy sodium bicarbonate is used. Initially for the selection of formulation Definitive screening design is used which allows to study the effect of large number of factors in relatively small experiment. The optimized formulation is tested for release rate, buoyancy, hardness, thickness, floating time, swelling study and release rate. These studies shows that optimized tablet remains in stomach for 24h and shows release rate of 91 which is very desirable. Priyanka Lekhwar | Dr. P. K. Sahoo | Ravindra Agarwal | Amit Sharma ""Development of Gastroretentive Floating Tablets Quetiapine Fumarate"" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-4 , June 2019, URL: https://www.ijtsrd.com/papers/ijtsrd24051.pdf
Paper URL: https://www.ijtsrd.com/medicine/other/24051/development-of-gastroretentive-floating-tablets-quetiapine-fumarate/priyanka-lekhwar
Preparation, In Vitro and In Vivo Characterization of Solid Dispersions of La...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Quantitative Determination of Deltamethrin in Milk, Blood and Urine of Domest...IOSR Journals
Deltamethrin among pyrethroids is used as an insecticide on different vegetables. Grass of sprayed field was provided to the domestic animals as a food. In order to determine deltamethrin quantitatively, animal samples like milk, blood and urine were extracted with n-hexane, partitioned and anhydrous Na2SO4 was added to the acetonitrile layer to remove the water contents. Silica gel column was used to cleanup deltamethrin with n-hexane and diethyl ether as a mobile phase. The column fractions were concentrated to 5 ml using rotary evaporator and analyzed using Gas Chromatography with Flame Ionization Detector (GC-FID).Deltamethrin solutions with concentrations ranging from 0.5-to 2.5-μg/ ml were used as calibration standards. The solution at 1.0μg/ml is used to confirm the claimed limit of detection (LOD).
In the present study, a gastro retentive micro particulate system was formulated with different Polymers by using
solvent evaporation technique. A series of 8 formulations was prepared based on 23 Design of experiments. The
formulated microspheres were evaluated flow characteristics, Practical yield (up to 80 %) and Encapsulation
efficiency (up to 94%). Scanning electron Microscopy confirmed their porous and spherical structure and the
particles were of the Size range of (65-525 μm). The release of drug at 1 hour and 8 hours’ time points were
taken as the measurable parameters for running the DOE experiments. According to design space Hollow
Microspheres formulated with Drug in the range of 50 to 70 mg/unit, Ethyl cellulose 7 cps in the range of 145 to
150 mg/unit and HPMC 5 cps in the range of 0.4 to 2 mg/unit were observed to have the best floating
characteristics and in vitro dissolution profile as per the preset target product profile. Stability studies showed no
significant change in the drug content in the formulations at 3 months accelerated condition. In this study
concluded that a micro particulate floating dosage form of an anti-infective drug can be successfully designed to
give controlled release and improved oral bioavailability.
KEYWORDS
Gastro retentive system, Ciprofloxacin Hcl, Ethyl Cellulose 7 cps, HPMC 5cps, Hollow microspheres.
Separation of Water to Concentrate Aloe Vera Juice:IJERA Editor
Aloe Vera is a succulent plant and is found in different arid areas. Due to its healing effect and soothing
properties it is being used in herbal medicines for years and its importance has grown due to use in cosmetic
products. It contains more than thirty active ingredients, which are utilized in cosmetic and pharmaceutical
industry. It also contains 98% water. To remove water from those active ingredient Reverse osmosis is used in
order not to thermally damage the active ingredients present in the juice. A reverse osmosis is a separation
technique which utilizes difference in pressure to segregate water from plant without damaging the active
ingredients present in the plant. This research is dedicated to evaluate the parameter for separation of water from
aloe Vera so that aloe Vera can be obtained in a form which can be utilized for different purposes such as
cosmetics and medicine. Osmosis technique is preferred over other conventional technique for the separation
purpose because it is not operated at high temperature, which will not damage the aloe Vera juice quality. Next
step in this research is the preserving, drying and analysis of this juice so that this product can be utilized in
versatile way.
This presentation gives brief idea about types of inhalation devices, types of DPIs devices, QbD elements, bioequivalence requirement in USA and EU, and marketed DPI products.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the quality control tests of parenteral as referred in the pharmacopoeia.
Thank you for reading. Hope it was of help to you.
UIPS,PU team
Polymeric Nanoparticles of Rifampicin were prepared by emulsion solvent evaporation technique using poly methyl methacrylate as polymer matrix and Poly vinyl alcohol as surfactant. Drug entrapped free flowing nanoparticles of Rifampicin were obtained after optimization using 32 factorial design and characterized for entrapment efficiency, particle size distribution, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and in vitro and stability studies. The PMMA nanoparticles had a small size (213 ± 0.72 nm), uniform size distribution. The effects of dependent variables drug-polymer ratio and surfactant concentration on particle size and encapsulation efficiency were studied. The drug and polymer were not interacting with each other. SEM studies revealed the spherical shape of nanoparticles and in vitro release studies showed sustained drug release. RIF-polymeric nanoparticles drug delivery system proved to be promising for anti-tubercular therapy.
Synthesis, Characterization and invitro Anti- inflammatory activity of 1, 3, ...SriramNagarajan19
Oxadiazole derivatives have played a vital part in the development of heterocyclic compounds. In this present work, a series of 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-thione derivatives (1-10) have been synthesized by Mannich reaction. The reaction progress of the synthesized compounds was checked by TLC. The structures of the newly synthesized compounds were confirmed by IR and 1H NMR spectral data. The in-vitro anti-inflammatory activity of 1, 3, 4-oxadiazole compounds (1-10) was assessed by HRBC Membrane Stabilization Method. Among the newly synthesized 1,3,4-oxadiazole derivatives, compounds OFP, OAP, OBNP, OPBNP, ORP, OUP, OPClBP, OFD, OAD and OBND possessed highly significant anti-inflammatory activity at a dose of 1000µg/ml when compared with standard, Diclofenac potassium.
Development of Gastroretentive Floating Tablets Quetiapine Fumarateijtsrd
The idea of the study is to prepare and characterize a sustain release floating tablets of Quetiapine Fumarate for Schizophrenia. Materials which are used in making of effervescent Tablets are hydroxy methylcellulose HPMC. For the buoyancy sodium bicarbonate is used. Initially for the selection of formulation Definitive screening design is used which allows to study the effect of large number of factors in relatively small experiment. The optimized formulation is tested for release rate, buoyancy, hardness, thickness, floating time, swelling study and release rate. These studies shows that optimized tablet remains in stomach for 24h and shows release rate of 91 which is very desirable. Priyanka Lekhwar | Dr. P. K. Sahoo | Ravindra Agarwal | Amit Sharma ""Development of Gastroretentive Floating Tablets Quetiapine Fumarate"" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-4 , June 2019, URL: https://www.ijtsrd.com/papers/ijtsrd24051.pdf
Paper URL: https://www.ijtsrd.com/medicine/other/24051/development-of-gastroretentive-floating-tablets-quetiapine-fumarate/priyanka-lekhwar
Preparation, In Vitro and In Vivo Characterization of Solid Dispersions of La...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Quantitative Determination of Deltamethrin in Milk, Blood and Urine of Domest...IOSR Journals
Deltamethrin among pyrethroids is used as an insecticide on different vegetables. Grass of sprayed field was provided to the domestic animals as a food. In order to determine deltamethrin quantitatively, animal samples like milk, blood and urine were extracted with n-hexane, partitioned and anhydrous Na2SO4 was added to the acetonitrile layer to remove the water contents. Silica gel column was used to cleanup deltamethrin with n-hexane and diethyl ether as a mobile phase. The column fractions were concentrated to 5 ml using rotary evaporator and analyzed using Gas Chromatography with Flame Ionization Detector (GC-FID).Deltamethrin solutions with concentrations ranging from 0.5-to 2.5-μg/ ml were used as calibration standards. The solution at 1.0μg/ml is used to confirm the claimed limit of detection (LOD).
Introduction to Topic Maps and Kamala. Learn to develop model-driven knowledge applications step by step. TAO of TopicMaps with Kamala including Typing, Schema and first Ontology constructs.
Design, Development, Evaluation and Optimization of Microballoons of TelmisartanSnehal Patel
Abstract: In present study an attempt was made to prepare microballoons of
Telmisartan by emulsion solvent diffusion technique for sustained delivery by
using polymers like Ethyl cellulose to extend the drug release for about 12 hours in
the upper GIT, which may result in enhanced absorption and there by improved
bioavailability. Formulation optimization of Telmisartan loaded microballoons was
carried out by using different concentration of Polyvinyl alcohol (PVA) and Ethyl
cellulose. Total 9 batches were formulated. All 9 batches were evaluated for
entrapment efficiency (EE) and buoyancy. Among all batches DP4 shows
maximum entrapment efficiency (EE) and buoyancy and was considered as
optimized formulation. DP4 batch was further used for process optimization. The
process optimization was carried out at three different stirring speeds i.e. 1300,
1500 and 1700 rpm for three different stirring time period i.e. 1hr, 2hr and 3 hr and
another 9 batches were formulated. Out of all the batches DP13 showed the
spherical shape of microballoons without formation of flakes. Optimized batch
DP13 was evaluated for Zeta Potential, Particle Size Distribution which show -
41.8mV and 1.344 μm particle size, SEM, XRD Analysis. Batch DP13 was
charged for stability and were placed in glass vials container and stored at ICH
storage condition (2°C - 4°C Refrigeration condition , 30 ± 2°C / 60% ± 5% RH ,
40 ± 2°C / 75% ± 5% RH ) for a period of 30 days. The samples were analyzed for
physical appearance, buoyancy and for the drug release after 30 days. After 1
months samples were withdrawn and microballoons showed no change in physical
appearances, buoyancy and drug release, which indicate that the microballoons
were stable.
Keywords: Telmisartan, Microballoons, Emulsion solvent diffusion technique,
Buoyancy, Entrapment Efficiency.
Design expert software assisted development and evaluation of cefpodoxime pro...Makrani Shaharukh
Cefpodoxime Proxetil is third generation, broad-spectrum Cephalosporin Antibiotic & it has an oral bioavailability of only 50% and biological half life 2 h so to improve it’s bioavailability sustain release matrix formulation was designed. Sustained release matrix tablets of Cefpodoxime Proxetil prepared by direct compression method based on combination of natural Acacia gum & Karaya gum polymers. 32 full factorial designs optimization study was carried out by using Design Expert Software to find the effect of independent variables, i.e., Acacia gum (X1) and Karaya gum (X2) concentration on dependent variables i.e., Hardness & % CDR. The drug excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical studies, in-vitro drug release, kinetic studies and stability studies. FTIR and DSC studies shown there was no interaction between drug and polymers. Matrix tablet of Cefpodoxime Proxetil were formulated well in term of hardness 5.07 ± 0. 5.93 ± 0.03 kg/cm2, thickness 2.25 ± 0.1 mm to 3.33 ± 0.3 mm, weight variation were within limits. In-vitro release studies show that almost 90 % of drug was release from all the formulation were within 12 h. Formulation F5 selected as a optimized one since it showed optimum hardness & sustained drug release within 12 h in comparison to other formulation. The F5 optimized formulations were subjected to stability studies and shown there were no significant changes in drug content, physicochemical parameters and release pattern. 32 full factorial design optimization technique was successfully used in this research work. Developed matrix tablets of Cefpodoxime Proxetil produced a sustained and effective drug release over a prolonged time frame that led to greater therapeutic efficacy.
DOI: 10.21276/ijlssr.2016.2.3.16
ABSTRACT- The present research article was described about the hypotriglycerdemic activity of Withania coagulans
bud extract. Withania coagulans Dunal belonging to the family Solanaceae is a small bush which is widely spread in
South Asia. The biological activity of with anolides from Withania coagulans has antihyperglycaemic activity and the
plant is commonly called as Indian cheese maker due to the milk coagulation characteristics of the bud. The present study
was to investigate preliminary studies shows satisfactory result. The chromatographic studies like TLC, HPTLC and
HPLC show good spot. HPTLC shows maximum height and area of 18.83%.HPLC shows maximum peak at 1.867
minutes having area coverage of 87.4%.The free radical scavenging activity of chloroform fraction (CF) of a crude drug
shows 510μg/ml of scavenging activity. The IC50 value for MTT assay was found to be 84.7μg/ml. The GLUT4 study
shows significant uptake of glucose. PPAR gamma activity regulation of glucose disposal and insulin sensitivity in the
skeletal muscles shows concentration dependence response using standard Pioglitazone. The bud of Withania coagulants
will be a promising medicine for more ailments.
Key-words- Withania coagulants, Hypotriglycerdemic, HPLC, HPTLC, GLUT-4, MTT assay
FORMULATION AND CHARACTERISATION OF TRANSDERMAL PATCHES OF PERINDOPRILSriramNagarajan19
Transdermal drug delivery system (TDDS) has been an increased interest in the drug administration via the skin for both local therapeutic effects on diseased skin (topical delivery) as well as for systemic delivery of drugs. The skin as a site of drug delivery, has a number of significant advantages over many other routes of drug administration, including the ability to avoid problems of gastric irritation, pH and emptying rate effects, avoid hepatic first-pass metabolism thereby increasing the bioavailability of drug, reduce the risk of systemic side effects by minimizing plasma concentrations compared to oral therapy, provide a sustained release of drug at the site of application; rapid termination of therapy by removal of the device or formulation, the reduction of fluctuations in plasma levels of drugs, and avoid pain associated with injections. The transdermal delivery can also eliminate pulsed entry into the systemic circulation, which might often cause undesirable side effects. Main objective of formulating the transdermal system was to prolong the drug release time, reduce the frequency of administration and to improve patient compliance. In the present study, five formulations were prepared using single polymer in different ratios, along with plasticizers and penetration enhancer. Finally it was concluded that Some formulations show formation of brittle patch due to insufficient amount of polymer and in some patches texture of patch is not elegant due to plasticizer concentration for patch preparation. So by increasing concentration of polymer and plasticizer, finally formulation-5 was considered as optimized formula for preparing transdermal patch of Perindopril, where it shown best drug release profile.
Membrane Stabilizing And Antimicrobial Activities Of Caladium Bicolor And Che...IOSR Journals
The crude methanol extracts of whole plant of Caladium bicolor (Aiton) Vent. and leaf of Chenopodium album L. as well as their pet-ether, carbon tetrachloride, chloroform and aqueous soluble fractions were evaluated for membrane stabilizing and antimicrobial activities. At concentration 1.0 mg/ml, the carbon tetrachloride soluble fraction of C. bicolor inhibited 43.92±1.63% and 38.08±0.83 % hypotonic solution and heat induced haemolysis of RBCs, respectively. Among the extractives of C. album, the aqueous soluble fraction inhibited 47.11±0.49 % and 36.73±0.76 % hypotonic solution and heat induced haemolysis of RBCs as compared to 72.79 % and 42.12 % by acetyl salicylic acid (0.10 mg/ml), respectively. C. bicolor test samples demonstrated zone of inhibition ranging from 6.0 to 20.0 mm. The chloroform soluble fraction showed the highest zone of inhibition (20.0 mm) against Staphylococcus aureus. The test samples of C. album displayed zone of inhibition ranging from 7.0 to 13.0 mm. The highest zone of inhibition (13.0 mm) was showed by the chloroform soluble fraction against Salmonella paratyphi
Hepatoprotective Effect of Cestrum parqui L. aerial parts and Phytochemical ...Jing Zang
This study deals with the investigation of hepatoprotective effect of 70% methanolic extract from Cestrum parqui aerial parts and determination of the bioactive components of the plant. The hepatoprotective effect of Cestrum parqui methanol extract (100, 500, 1000 mg/kg) was analysed on carbon tetrachloride (CCl4)-induced acute liver injury. The administration of a single dose of 40% CCl4 (1ml/kg b.w.) causes an increase in the activities of serum alanine aminotransferase (ALT) and aspirate aminotransferase (AST) enzymes and so pretreated orally of a dose from Cestrum parqui methanol extract (100, 500, 1000 mg/kg) and silymarin (200 mg/kg) for three consecutive days prior to The administration of a single dose of CCl4 significantly prevented the increase in the activities of these enzymes. Histological analysis showed that Cestrum parqui methanol extract at doses of 500 and 1000 mg/kg and silymarin reduced the incidence of liver lesions including vacuole formation, neutrophil infiltration and necrosis of hepatocytes induced by CCl4. The extract cause a negative result on the antioxidative enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRd) and decreased malondialdehyde (MDA) level in liver, as compared to those in the CCl4-treated group and this suggests that the hepatoprotective activity of the extract is due to the antioxidant effect of the extract. Phytochemical analysis of the methanol extract from Cestrum parqui aerial parts showed that it contained different phytoconstituents, flavonoids, tannins, saponins, alkaloids, terpenes and carbohydrates.
ABSTRACT- Mosquito-borne diseases have intruded the globe since immemorial time. The present scenario for
commanding the mosquitoes is aimed at application of target and stage-specific, cost-effective and biodegradable
phytoproducts. Plant extracts are safer for non-target organisms including man. Plant based formulations would be more
feasible environmental products with proven potential as insecticide. Therefore, in the present study of larvicidal
activity of biologically active compound Apigenin extracted from leaf of Jatropha gossypifolia against the filarial
vector, Culex quinquefasciatus was studied. Standard WHO protocols with minor modifications was adopted for the
larvicidal bioassay. The active compound Apigenin extracted through ethyl alcohol solvent from the leaf of Jatropha
gossypifolia plant of family Euphorbiaceae was administered for 24h or 96h to the larvae of Culex quinquefasciatus.
Exposure of larvae over 24h to sub-lethal doses (40% and 80% of LC50) of apigenin, significantly (P<0.05) altered the
level of total protein, total free amino acid, glycogen and activity of enzymes acetyl cholinesterase, acid and alkaline
phosphatase activity in whole body tissue of Culex quinquefasciatus larvae. The alterations in all these biochemical
parameters were significantly (P<0.05) time and dose dependent.
Key-words- Jatropha gossypifolia, Euphorbiaceae, Culex quinquefasciatus, biochemical effects, Wuchereria bancrofti
IN-SILIC0 STUDY OF CURCUMIN, DEMETHOXYCURCUMIN AND XANTHORRIZOL AS SKIN WHITE...Jing Zang
Curcumin, demetoxycurcumin and xanthorrhizol are an active compounds contained in temulawak (Curcuma xanthorrhiza) which have activity in inhibiting the tyrosinase enzyme and α-melanocyte stimulating hormone (α-MSH ) in vitro. Docking simulation was done to determine and visualize the interaction of the three compounds with the tyrosinase enzyme and α-MSH. The results of docking simulations showed that the three compounds can interact spontaneously with the tyrosinase enzyme and α-MSH. On the tyrosinase enzyme, xanthorrhizol interact most easily through the formation of hydrogen bonds with Asn205. On the α-MSH, demethoxycurcumin interact most easily through the formation of two hydrogen bonds with His3 and Arg5. With the inhibitory effect on the enzyme tyrosinase and α-melanocyte stimulating hormone (α-MSH) means preventing the formation of skin coloring pigment melanin, indicating that the three compounds studied can be applied as skin whitening agents.
ABSTRACT
Overactive bladder (OAB) is a prevalent condition which has an adverse effect on quality of life. The presence
of urgency incontinence confers significant morbidity above and beyond that of OAB sufferers who are
continent. The primary treatment for OAB and urgency incontinence is a combination of behavioral measures
and antimuscarinic drug therapy. The ideal antimuscarinic agent should effectively relieve the symptoms of
OAB, with the minimum of side effects; it should be available as a once-daily sustained release formulation
and in dosage strength that allows easy dose titration for the majority of sufferers. Solifenacin succinate was
launched in 2005 and has been shown in both short and long term clinical trials to fulfill these requirements.
Solifenacin is a competitive M3 receptor antagonist with a long half-life (45-68 hours). It is available in two
dosage strengths namely a 5 or 10 mg once-daily tablet. The efficacy and tolerability of solifenacin for the
treatment of all symptoms of OAB has been evaluated in a number of large, placebo controlled, randomized
trials. Long-term safety, efficacy, tolerability and persistence with treatment have been established in an open
label 40 week continuation study.
KEYWORDS
Solifenacin, Urinary incontinence, Overactive bladder and Wet granulation method.
Inhaler Devices For Cannabinoids Controlled Delivery Cannatech 2018Philippe Rogueda
Let's talk about inhaled and intranasal devices for
cannabinoid delivery: I will debunk quacks, bring
in science and see what works and what does not.
No prisoners will be taken. Technology will either
stand scrutiny or be lampooned.
e-Cigarettes: lessons for Inhalation technologistsPhilippe Rogueda
e-Cigarettes: lessons for Inhalation technologists
Electronic cigarettes (ECs), or e-cigarettes, produce aerosols through heating and vaporizing solutions. They are marketed for recreational use and are not much regulated. They share a common purpose as inhalation products: they produce aerosols intended to be orally inhaled. ECs are much cheaper and more popular than pharmaceutical inhalers. Their efficiency at delivering nicotine satisfies their users, yet, their delivery mechanism is a mystery. A selection of vaping devices available in Hong Kong were tested in vitro with commercial e-liquids and laboratory formulations based on glycerin. Their aerosolisation profiles were studied by laser scattering and were compared to tobacco industry claims. Conclusion: nicotine is more likely to be delivered via the buccal cavity than the lung. The array of flavourings and formulation excipients used is as broad as it is exotic (bubble gum, butterscotch, gourmet cinnamon, pie crust, root beer, propylene glycol and glycerin), it is an unheard of open-access worldwide clinical trial of excipients: exploring and monitoring it is a must.
Full slides are available via the Aedestra Ltd website (www.aedestra.com) or on slideshares: http://www.slideshare.net/progueda/ecigarettes-lessons-for-inhalation-technologists, and on request: info@aedestra.com
Aedestra is a product development company in the field of inhaled drug product. We make developing inhaled products easy, so you can focus on delivery. We drive initiatives; you realise opportunities. We can help you develop the right product in the right way by providing strategic and technical expertise: reducing cost, time and risk. Get in touch now to expand and develop your inhaled portfolio.
Philippe Rogueda (1), Philip Chi Lip Kwok (2), Lu Hou (2)
(1) Aedestra Limited, 11/F, Rykadan Capital Tower, 135-137 Hoi Bun Road, Kwun Tong, Kowloon, Hong Kong SAR
(2) Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR
The future of Gx DPI Inhalers - Presented Mgt Forum 16 June 2016 London, UK.
Topics include:
-what's happening: latest filings, regulations, players
-where it is going: technology, market trends, clinical trials
-future opportunities: products, telehealth, triple therapies
-east-west influence: how India and China are shaping the Gx DPI market.
Full slides available on request: info@aedestra.com
Has innovation in inhalation drug delivery run out of steam?Philippe Rogueda
Has innovation in inhalation drug delivery run out of steam?
Slides presented at the Chiesi I3 innovation seminar, 10 July 2014 at Celtic Manor Resort, Wales, U.K.
Choosing the right device: The case for nebulisersPhilippe Rogueda
Nebulisers are the oldest inhalation delivery devices, yet have been confined to the treatment of cystic fibrosis and clinical settings. Choosing a nebuliser can be bewildering, because of the choices and combinations available, and because nebules+nebuliser combinations are not prescriptive. This is further compounded by the different methods and experimental set-ups used to test nebulisers, that could benefit from harmonisation.
The term nebulisers covers a range of technology: from jet to mesh nebulisers, from home to hospital setting, from daily use to critical care, paediatrics to geriatrics. No wonder the technology choices can seem too rich to contemplate. This wealth of technology shows that nebulisation delivery is very much alive and can answer many needs of the respiratory delivery community. New devices and technologies are developed regularly, the Respimat, MicroDose dry powder nebuliser and Supraer are three examples of such advances which will we review.
In this paper, we will take a stand in favour of nebulisers, and show you how to structure your approach to select the most appropriate device for your needs. This will be done in 4 steps:
-Criteria list drafting
-Technology and performance review
-Hints and tips to screen through performance data and marketing smoke-screens
-Review of alternative technologies
Is There A Future For Triple Therapy In Copd Ph Rogueda 14 April 2011Philippe Rogueda
An extensive review of the potential of triple therapy in the treatment of COPD, spanning Clinical Trials, Clinical Practice, Commercial insight and Intellectual Property
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
6. Surface Modified Voriconazole Dry Powder Inhalable Formulation for the Treatment of Invasive Pulmonary
Aspergillosis
Sumit Arora1, 2, 3
, Mehra Haghi2, 4
, Paul M. Young2
, Michael Kappl3
, Daniela Traini2
& Sanyog Jain1
1
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical
Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali) Punjab- 160062 INDIA
2
Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical
School, The University of Sydney, NSW 2037, Australia
3
Max Planck Institute for Polymer Research, 55128 Mainz, Germany
4
School of Pharmacy, Graduate School of Health, University of Technology, Sydney, NSW 2007, Australia
Summary
Background: Invasive pulmonary aspergillosis (IPA) is a severe disease in immunocompromised patients with
extremely high mortality rate. Voriconazole (VRZ) is a first line treatment drug for IPA, conventionally administered
orally or intravenous, resulting in a plethora of drug-drug interactions and off-target toxic effects. In the present
research work, we developed and characterised a highly dispersible dry powder inhalable formulation of VRZ using L-
Leucine as a dispersibility enhancer. Methods: VRZ and L-Leucine in varying concentrations were dissolved in
ethanol-water (70:30% v/v) and spray dried to yield inhalable dry powders. Powders were characterised in terms of
particle size, morphology and aerosol performance using the low resistance RS01 dry powder device with next
generation cascade impactor. Storage stability (chemical stability and aerosol performance) of the optimized
formulation was evaluated for 3 months. Calu-3 sub bronchial epithelial cell line was used to study cell viability (MTS
test). Finally, in vivo pharmacokinetic studies in mice were carried out to determine the lung bioavailability of the
optimised formulation. Results: Dry powder comprising VRZ (8 mg/mL) and L-Leucine (2 mg/mL) was found to be
suitable for inhalation therapy. Powder exhibited a volume median diameter of 2.64 ± 0.05 µm and superior
aerosolisation with MMAD of 3.79 ± 0.02 µm and fine particle fraction (% aerosol < 5 µm) of 60.00 ± 0.94 %. Powder
exhibited irregular morphology and demonstrated physico-chemical stability of up to 3 months at room temperature.
Formulation was found to be non-cytotoxic to Calu-3 cells. Moreover, lung bioavailability in murine model showed the
ability of inhaled formulation to attain higher concentration of VRZ in lungs as compared to intravenous administration.
Conclusion: A highly respirable dry powder VRZ formulation was developed for the treatment of IPA.
Introduction
Aspergillus fumigatus, the opportunistic fungi, causes IPA particularly in immunocompromised patients such as those
suffering from hematologic malignancies, cancer, AIDS and those undergoing solid organ transplantation.[1]
This
results in substantial mortality (nearly 80%) and huge financial burden. VRZ is the drug of choice for the treatment of
IPA.[2]
Oral or intravenous administration of VRZ have been associated with high inter- and intra-patient
pharmacokinetic variability, poor lung distribution particularly in patients undergoing lung transplantation, alteration of
enzyme levels in liver leading to numerous, sometimes lethal drug-drug interactions as well as the off-target toxic
effects. [3]
Pulmonary delivery of high doses of VRZ represent a potential viable therapeutic option for the targeted treatment of
IPA, whilst minimising systemic exposure and related toxicity.
Methods and Materials
VRZ was supplied by Ranbaxy Laboratories (Gurgaon, India) and L-Leucine was purchased from Sigma-Aldrich
(Sydney, Australia). Calu-3 cell line (HTB-55) was purchased from the American Type Cell Culture Collection (ATTC,
Rockville, USA). Dulbecco’s modified Eagle’s medium and L-glutamine from Invitrogen (Sydney, Australia). All
solvents were of analytical grade and used as supplied (Biolab, Victoria, Australia)
Preparation of L-Leucine modified VRZ microparticles
For the preparation of respirable particles, VRZ (8 mg/mL) and L-Leucine (2 mg/mL) were dissolved in ethanol-water
(70:30% v/v) and spray dried using a Buchi Mini Spray Dryer B-290 at the following conditions: feed concentration of
10 mg/ml, inlet temperature 125°C, outlet temperature was 78°C, atomiser 700 L/h, aspirator 40 m3/h and feed rate
5%.
7. Morphological and Particle Size Analysis
Morphology of the spray dried products was studied using a scanning electron microscope (SEM, JMC, 6000 JEOL,
Japan). Samples were coated with 15 nm gold (Sputter coater S150B, Edwards High Vacuum, Sussex, UK) and
images were taken at random locations. Size distribution of the VRZ alone and VRZ-Leucine particles was analysed
using laser light diffraction (Mastersizer 3000, Malvern, United Kingdom) using the Scirocco dry dispersion unit with a
feed pressure of 4 bar and a refractive index of 1.62 for VRZ.
In vitro aerosol performance characterisation
Aerosol performance of the spray dried products (5mg in a size 3 gelatin capsule) was evaluated using an RS01 dry
powder inhaler device (Plastiape, Italy) with a next generation impactor (NGI) operated at a flow rate of 60 L/min for 4
sec. Under these operating conditions, the volume of air drawn through the inhaler corresponds to 4 L, which
represent the normal inspiratory capacity of an average sized-adult male of 70 kg. Samples were recovered from each
stage of the NGI and the VRZ content was determined by a validated HPLC method. Mass median aerodynamic
diameter (MMAD), geometric standard deviation (GSD) and fine particle fraction (FPF) (% aerosol < 5 µm) of the
emitted dose were calculated from the NGI results.
Short Term Storage Stability
Storage stability of optimised formulation was determined as per USFDA guidelines.[4]
Optimised formulation was
stored under two conditions: Condition 1: 25ºC and 60% RH and Condition 2: 40ºC and 75% RH in climate controlled
cabinet and assessed for their chemical stability and aerosol performance for up to a 3 months.
Calu-3 cell viability
Calu-3 cell viability for the spray dried VRZ only and L-Leucine modified VRZ was carried out according to the
previous published method.[5]
Briefly, cells were seeded at the density of 5×104
cells/well, incubated overnight and
treated with the increasing equivalent concentrations of VRZ (1.2 nM to 300 µM) for both the spray dried products for
72 h. 20 μL of the CellTiter 96®
Aqueous assay (MTS reagent) (Promega, Madison, USA) was added to each well to
assess the viability of the cells. The plates were incubated for 3 hours at 37°C in humidified 5% CO2 atmosphere. The
absorbance was measured at 490 nm using a Wallac 1420 VICTOR 2 Multilabel Counter (Wallac, Waltham, USA).
In vivo lung bioavailability
Animal experimentation were carried out after obtaining ethical clearances from the Institutional Animal Ethics
Committee of the National Institute of Pharmaceutical Education and Research (NIPER), S.A.S Nagar India. Balb/c
mice of either sex (20-25 g) were divided in two groups: Group 1 (40 animals) were dosed with optimised inhalable
formulation (target VRZ dose 10 mg/kg) using a custom built in house apparatus while Group 2 (40 animals) received
an intravenous VRZ dose (10mg/kg). At predetermined time points (10 min, 30 min, 1, 2, 4, 8, 12 and 24 h), five mice
were euthanised with pentobarbital injection. Whole blood was collected following cardiac puncture and lungs were
also excised and stored at -20ºC until further analysis. VRZ was quantified by validated HPLC method following
homogenisation of lung tissue according Beinborn et al
protocol with minor modifications.[6]
Results and Discussion
Dry powder formulation containing VRZ (8 mg/mL) and
L-Leucine (2 mg/mL) was found to have optimum
characteristics for inhalation therapy. Figure 1 shows
the representative scanning electron microscopy images
of spray dried VRZ alone and optimised L-Leucine
modified VRZ microparticles (VRZ_LEU_20). Spray
dried VRZ exhibited irregular plate like morphology with
crystalline structure. However, with the inclusion of L-
Leucine in the spray drying feed, the morphology of
composite particles were found to be more regular and
spherical. Particle size analysis by laser diffraction
indicated median volume diameters (dv0.5) of 4.52 ±
0.07 μm and 2.64 ± 0.05 (n=3) for VRZ alone and VRZ_LEU_20, respectively.
10 µm
B
10 µm
A
Figure 1 Representative scanning electron microscopy
images (A) Spray dried VRZ alone and (B) VRZ LEU 20
8. The in vitro aerosolisation performance of the
spray dried VRZ alone and VRZ_LEU_20 is
shown in Figure 2. The MMAD and FPF (%
aerosol < 5µm) of VRZ alone was found to be
6.12 ± 0.18 µm and 20.86 ± 1.98 %,
respectively, while for VRZ_LEU_20, it was
found to be 3.79 ± 0.02 µm and 60.00 ± 0.94
%, respectively. Incorporation of L-Leucine
clearly lead to an improvement (p<0.05) of the
aerosolisation performance of the spray dried
composite particles. L-Leucine probably
increased aerosol performance by reducing
particle agglomeration, thus promoting particle
deagglomeration and delivery.[7]
The optimised formulation (VRZ_LEU_20) was
found to be chemically stable in terms when
stored for 3 months at room temperature as
well as accelerated storage conditions. No
significant change (p>0.05) in the aerosol
performance of VRZ_LEU_20 was observed
when powders were stored at 25ºC and 60%
RH for three months. However, nearly 10%
decrease in FPF (% aerosol < 5µm) of
VRZ_LEU_20 was observed when it was stored at 40ºC and 75% RH. This clearly revealed that the optimised
formulation should be protected from high humidity and high temperature conditions for its optimal performance.
The dose response cytotoxicity profile of spray dried VRZ alone and VRZ_LEU_20 on Calu-3 cells is shown in Figure
3. Calu-3 cells could tolerate (nearly 90% cell viability) a wide range of VRZ concentrations, from 1.2 nM to 300 µM
indicating that it can be safely administered to the lungs in this range.
Figure 4 shows the plasma and lung VRZ concentration time profiles following intravenous administration of VRZ
solution and inhalation delivery of optimised formulation (VRZ_LEU_20). In vivo lung bioavailability studies in murine
model suggested that inhalable VRZ formulation (VRZ_LEU_20) was able to reach higher VRZ concentrations in the
lungs compared to intravenous administration, thereby, enhancing the therapeutic effect of the drug at the disease
site. Total lung VRZ exposure AUC 0-∞ was found to be 524.31 ± 170.05 mg/kg h wet lung weight and 32.89 ± 9.95
mg/kg h wet lung weight when administered through inhalation and intravenous delivery, respectively. Similarly, Cmax
in the lungs was found to be 1095.25 ± 277.92 µg/g and 13.48 ± 5.35 µg/g when VRZ was administered through
inhalation and intravenous route of administration, respectively.
Concentration of VRZ (mM)
10-1
100
101
102
103
104
105
106
Calu-3CellViability(%)
60
80
100
120
140
160
(A)
Concentration of VRZ_LEU_20 (mM)
10-1 100 101 102 103 104 105 106
Calu-3CellViability(%)
40
60
80
100
120
140
(B)
D
eviceThroat
Stage
1Stage
2Stage
3Stage
4Stage
5
Stage
6Stage
7Stage
8
0
10
20
30
40
50
VRZ
VRZ_LEU_20
%VRZDeposition
Figure 2 Aerodynamic particle size distribution profile of VRZ and
VRZ_LEU_20 with NGI at a flow rate of 60 L/min. For each stage,
VRZ is shown as a percentage of its total actual recovered
amount. (n=3; mean ± SD)
Figure 3 The effect of VRZ (A) and VRZ_LEU_20 (B) on Calu-3 Cell viability following 72 h VRZ
treatment. (n=3; mean ± SD)
9. Conclusions
IPA is a serious disease in immunocompromised patients with unmet medical needs. Pulmonary delivery of high dose
of VRZ could serve as attractive therapeutic alternative for the treatment of IPA. The present study confirmed the
suitability of L-Leucine modified VRZ formulation for the inhalation therapy. The formulation was found to be high
dispersible, stable for 3 months under room temperature conditions and non-toxic to the pulmonary epithelial cells. In
addition, murine pharmacokinetics studies revealed that inhalable VRZ formulation can achieve higher concentrations
of VRZ in the lungs as compared to conventional intravenous administration, thereby, may lead to better therapeutic
outcome.
Acknowledgments
Authors are thankful to Director, NIPER, Woolcock Institute of Medical Research and Max Planck Institute for Polymer
Research for providing necessary infrastructure facilities. SA is the recipient of an Endeavour Research Fellowship
and German Academic Exchange Service (DAAD) Scholarship from the Australian and German government,
respectively, in 2014 and the work was carried out as a part of these fellowships.
References
1. Patterson, T. F: Advances and challenges in management of invasive mycoses. Lancet 2005; 366: pp1013-1025.
2. T.J. Walsh, E.J. Anaissie, D.W. Denning, R. Herbrecht, D.P. Kontoyiannis, K.A. Marr, V.A. Morrison, B.H. Segal,
W.J. Steinbach, D.A. Stevens, J.A. van Burik, J.R. Wingard, T.F. Patterson, A: Infectious Diseases Society of,
Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America, Clin Infect Dis
2008; 46: pp 327-360.
3. Hilberg, O., Andersen, C. U., Henning, O., Lundby, T., Mortensen, J., Bendstrup, E: Remarkably efficient inhaled
antifungal monotherapy for invasive pulmonary aspergillosis. Eur Respir J 2012; 40: pp 271-273.
4. F. Draft, Guidance for industry—metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products,
Chemistry, manufacturing, and controls documentation Oct. 1998.
5. Haghi, M., Young, P. M., Traini, D., Jaiswal, R., Gong, J., Bebawy, M: Time- and passage-dependent
characteristics of a Calu-3 respiratory epithelial cell model. Drug Dev. Ind. Pharm. 2010; 36: pp 1207-1214.
6. N.A. Beinborn, J. Du, N.P. Wiederhold, H.D. Smyth, R.O. Williams, 3rd
: Dry powder insufflation of crystalline and
amorphous voriconazole formulations produced by thin film freezing to mice. Eur J Pharm Biopharm 2012; 81: pp 600-
608
7. L. Cruz, E. Fattal, L. Tasso, G.C. Freitas, A.B. Carregaro, S.S. Guterres, A.R. Pohlmann, N. Tsapis: Formulation
and in vivo evaluation of sodium alendronate spray-dried microparticles intended for lung delivery. J Control Release
2011; 152: pp 370-375.
Time (h)
0 5 10 15 20 25 30
VRZConcentration(µg/g)
0.01
0.1
1
10
100
1000
Lung (IV)
Lung (IL)
Time (h)
0 5 10 15 20 25 30
VRZConcentration(µg/ml)
0.01
0.1
1
10
100
Plasma (IV)
Plasma (IL)
(A) (B)
Figure 4 Voriconazole (VRZ) concentration–time plots following intravenous (IV) and inhalation (IL)
delivery (mean ± standard deviation) (n = 5) for (A) Plasma and (B) Lung.
12. Background of the Research -
Discontent
Rationale for Selection of the Drug
and Formulation
Experimental Results: Formulation Design and
Characterisation
Conclusion and
Acknowledgements
8
13. "The person who
takes medicine must
recover twice, once
from the disease and
o n c e f r o m t h e
medicine."
- William Osler, M.D.
9
14. 10
IPA is an increasingly common opportunistic fungal infection usually
occurring in patients with neutropenia and/or corticosteroid exposure. The
lungs are involved in about 85% of cases of IPA. Mortality rate exceeds 50%
in neutropenic patients and reaches 90% in haematopoietic stem-cell
transplantation recipients
Inhalation of
spores
Infected
Lungs
http://www.jpmoldcontrol.com/faq/health-hazards.shtml Sabins et al; Lung
India, 2012, 29(2); pg 185-186
15. N N
F CH3
N
N
N
F
F
OH
M o l e c u l a r
Formula
C16H14F3N5O
M o l e c u l a r
Weight
349.311 g/mol
pKa 1.76
Log P 1.8
Mel6ng Point 127-130 °C
Solubility Low water solubility (0.7
VORICONAZOLE
(VRZ)
11
Commericially available VRZ
Formulations administered as
tablet or an intravenous injection
20. 5 µm
VRZ
5 µm
VRZ_LEU
_10
5 µm
VRZ_LEU_20
5 µm
VRZ_LEU_30
Scanning electron microscopic images of (A) VRZ (B)
VRZ_LEU_10 (90:10) (C) VRZ_LEU_20 (80:10) and (D) 16
21. 17
-18
-8
2
10 60 110 160
VRZ
VRZ_LEU_10
VRZ_LEU_20
VRZ_LEU_30
50 100 150
-20
-10
0
Temp (ºC)
HeatFlow(mW)
10 20 30 40
2θ Scale
Intensity
(ArbitraryUnits)
VRZ
VRZ_LEU_10
VRZ_LEU_20
VRZ_LEU_30
Leucine
10 20 30 40
2θ ScaleIntensity
(ArbitraryUnits)
A B
A) DSC Thermograms of spray dried VRZ formulations and B) Powder X-
Ray Diffractograms of spray dried VRZ formulations
L-leucine interferes with the crystallization of VRZ during the
spray drying
132.6
°C
22. Aerodynamic particle size distribution profile of L-leucine
modified VRZ microparticles with NGI at a flow rate of 60
L/min. For each stage, VRZ is shown as a percentage of
its total actual recovered amount. (n=3; mean ± SD)
Next Generation Impactor
(NGI)
18
DeviceThroat
Stage1(>
8.06µm
)
Stage2(8.06
-4.46µm
)
Stage3(4.46
-2.82µm
)
Stage4(2.82
-1.66µm
)
Stage5(1.66
-0.94µm
)
Stage6(0.94
-0.55µm
)
Stage7(0.55
-0.34µm
)
Stage8(<
0.34µm
)
0
10
20
30
40
50
VRZ
VRZ_LEU_10
VRZ_LEU_20
VRZ_LEU_30
%DrugDeposition
Operating
Conditions
Flow Rate: 60L/
min
Time of operation:
4s
23. Formulati
on
MMAD GSD
FPF (<
5µm)
EDF (%) FPD (µg)
VRZ
6.12 ±
0.18
1.60 ± 0.02 20.86 ± 1.98 57.77 ± 2.01 703.92 ± 96.56
VRZ_LEU_
10
4.54 ±
0.08
1.49 ± 0.02 50.97 ± 1.82 72.07 ± 2.31 1419.79 ± 50.49
VRZ_LEU_
20
3.79 ±
0.02
1.70 ± 0.01 60.00 ± 0.94 81.88 ± 0.56 1892.98 ± 156.67
VRZ_LEU_
30
3.97 ±
0.35
1.66 ± 0.04 58.73 ± 5.50 79.95 ± 1.75 1583.98 ± 139.10
Formulation with 20% L-leucine showed optimal aerodynamic
properties and was selected for further cell and in vivo studies.
MMAD – Mass Median Aerodynamic Diameter GSD – Geometric
Standard Deviation
FPF – Fine Particle Fraction EDF – Emitted Dose Fraction
FPD – Fine Particle Dose
19
24. 20
Storage
Condition
MMAD
(µm)
GSD
FPF (%) (<
5µm)
EDF (%) FPD (µg)
25ºC and 60%
RH
3.71 ± 0.16
1.73 ±
0.03
60.26 ± 2.03
77.32 ±
3.43
1942.79 ±
76.28
40ºC and 75%
RH
4.38 ± 0.13
1.62 ±
0.01
50.78 ± 4.02
77.98 ±
0.58
1371.40 ±
208.38
Aerosol property of optimised formulation (VRZ_LEU_20) after storage at room and
accelerated conditions for 3 months. Data are represented as mean ± S.D (n = 3)
DeviceThroatStage
1Stage
2Stage
3Stage
4Stage
5Stage
6Stage
7Stage
8
0
10
20
30
3 month 25ºC and 60%RH
3 month 40ºC and 75%RH
0 month
%VRZDeposition
25. 21
Haghi, M., et al. (2014) Pharm Res 31:1779–1787
Schematic Diagram of In vitro Calu-3 cell
integrated Impactor
26. 22
Statistical analysis revealed no significant difference between release
profile of VRZ and VRZ_LEU_20. Co-spraying L-leucine with VRZ
did not influence the dissolution of VRZ.
27. Even at the highest concentration of VRZ and VRZ_LEU, cell
viability was above the 80%.
96 well plate 5 X 104 cells per well
1.2 nM to 300 µM
72 hours incubation Absorbance 490 nm
10-6
10-5
10-4
10-3
10-2
10-1
100
60
80
100
120
140
160
Concentration of VRZ (mM)
Calu-3viability(%)
10-6
10-5
10-4
10-3
10-2
10-1
100
60
80
100
120
140
Concentration of VRZ_LEU (mM)
Calu-3viability(%)
23
28. Voriconazole (VRZ) concentration–time plots following intravenous (IV) and inhalation (IL) delivery
(mean ± standard deviation) (n = 5) for (A) Plasma, (B) Lung, (C) Liver, (D) Kidney and (E) Spleen at
the dose of 10 mg/kg in mice model. 24
29. 25
Route/
Parameter
Plasma Lung Liver Kidney Spleen
Inhalation
AUC 0-∞ (mg/L h) 26.22 ±
9.69
N/D N/D N/D N/D
AUC 0-∞ (mg/kg h) N/D 524.31 ±
170.05
59.09 ±
18.81
47.61 ± 8.65 23.19 ± 4.75
C0 (µg/ml or µg/g) 0 1095.25 ±
277.92
0 0 0
Cmax (µg/ml or µg/
g)
8.92 ±
2.25
N/D 13.58 ±
3.97
10.03 ± 3.44 3.64 ± 0.97
Tmax (h) 0.167 N/D 2 2 2
Intravenous
AUC 0-∞ (mg/L h) 47.12 ±
7.77
N/D N/D N/D N/D
AUC 0-∞ (mg/kg h) N/D 32.89 ± 9.95 92.74 ±
20.52
66.49 ±
15.54
36.44 ± 7.77
C0 (µg/ml or µg/g) 16.13 ±
8.31
0 0 0 0
Cmax (µg/ml or µg/
g)
N/D 13.48 ± 5.35 25.14 ±
8.20
16.46 ± 5.66 7.88 ± 1.29
Tmax (h) 0 1.1 ± 0.55 1 1 1
Pharmacokinetic parameters of VRZ following inhalation and
intravenous administration in BALB/c mice (mean ± standard
deviation; n=5)
AUC0–∞, area under the concentration–time curve from time 0 to infinity; C0, Concentration at
time = 0 h; Cmax, maximum observed VRZ concentration; Tmax, time to Cmax; N/D, not
determined. Values for plasm is presented as per mL or per L while for tissue homogenates,
values are presented in per g or per Kg.
This clearly demonstrates that an inhalable VRZ dry powder delivered directly to the lung
results in high VRZ concentrations whilst simultaneously reducing its systemic exposure to
other tissues such as liver, kidney and spleen and hence reducing associated toxicities.
30. Spray dried VRZ formulation as inhalation powder
could be used as a new potential therapeutic
approach for the targeted treatment of Invasive
Pulmonary Aspergillosis
26
Further in vivo efficacy studies in animal models are
needed to be performed
31. 27
Supervisor
s
Post Doc
D r . M e h r a
Haghi
Dr. Paul M
Young
Dr. Daienla Traini
R e s p i t e c h
Group
Dr. Sanyog Jain
C P N
Lab
Dr. Michael
Kappl
AKA Butt
“None of us is as smart as all of us.” - Japanese Proverb