Verapamil Research Articles

A rapid and versatile microfluidic method for the simultaneous extraction of polar and non-polar basic pharmaceuticals from human urine

In sample preparation, simultaneous extraction of analytes of very different polarity from biological matrixes represents a challenge. In this work, verapamil hydrochloride (VRP), amitriptyline (AMP), tyramine (TYR), atenolol (ATN), metopropol (MTP) and nortriptyline (NRP) were used as basic model analytes and simultaneously extracted from urine samples by liquid-phase microextraction (LPME) in a microfluidic device. The model analytes (target compounds) were pharmaceuticals with 0.4 < log P < 5. Different organic solvents and mixtures of them were investigated as supported liquid membrane (SLM), and a mixture of 2:1 (v/v) tributyl phosphate (TBP) and dihexyl ether (DHE) was found to be highly efficient for the simultaneous extraction of the non-polar and polar model analytes. TBP reduced the intrinsic hydrophobicity of the SLM and facilitated extraction of polar analytes, while DHE served to minimize trapping of non-polar analytes. Sample and acceptor phase composition were adjusted to pH 12 and pH 1.5, respectively. Urine samples were pumped into the microfluidic system at 1 μL min-1 and the extraction was completed in 7 min. Recoveries exceeded 78% for the target analytes, and the relative standard deviation (n = 4) was below 7% in all cases. Using five microliters of SLM, the microfluidic extraction system showed good long-term stability, and the same SLM was used for more than 18 consecutive extractions.

Drug combination study of novel oxorhenium(V) complexes

Three Re(V) complexes of structural formulas [ReOCl2L(PPh3)], where L is pyridine-2-carboxylic acid (C1), 3-methyl-pyridine-2-carboxylic acid (C2) and 6-methyl-pyridine-2-carboxylic acid (C3) were synthesized and characterized using NMR, IR spectroscopy and mass spectrometry. Crystal structures of all three complexes have been additionally confirmed by X-ray analysis. The biological activity has been investigated in the panel of tumor cell lines A549, PANC-1, MDA-MB-231, MCF-7, LS-174, EAhy.926 and one in non-tumor cell line MRC-5. Only C1 showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cells MDA-MB-231 with IC50 68.90 ± 1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.84 ± 2.3 μM. Both cell lines are characterized by a highly invasive and resistant phenotype. Drug combination studies in PANC-1 cells with C1 and Verapamil hydrochloride (VRP), which is the established inhibitor of efflux transporter P-glycoprotein (Pgp), revealed enhancement of antiproliferative action of the complex in a dose-dependent manner, and slight arrest of cell cycle in the S phase. Also, a depletion of the glutathione (GSH) level by L-buthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) caused an increase of activity of C1 to the IC50 57.67 ± 6.51 (μM). A morphological analysis in PANC-1 cells by dual acridine orange/ethidium bromide staining, revealed apoptotic potential of complex C1 and a slower kinetic of cell death induction, suggesting a different mechanism of action compared to cisplatin.

Formulation and Characterization of Mucoadhesive Microspheres of Oxazolidines Class Drug for the Treatment of Loosen Enteritis

This study aimed to developed novel fast disintegrating sustained release pellets containing tablet by using Fluidized Bed processor. Verapamil HCl used as a model drug for the formulation. Fluidized bed processor was used for coating of drug and polymer on the sugar spheres. To overcome the problem of swallowing for paediatric, geriatric, psychiatric, bedridden patients, uncooperative patients or for active patients who are busy and travelling and may not access to we aim to formulate the fast-disintegrating tablet. The superdisintigrant are commonly use like cross povidone, sodium starch glycolate which disintegrate tablet rapidly. It is assumed that, after the disintegration of tablets, pellets within tablets which are reside in GIT for several hours and gradually released a drug in controlled way. Eudragit RS 30D and ethyl cellulose were used as a sustained release polymer. Coating of spheres with sustained release film is achieved by bottom spray processor of FBP. Proper pellets coating film thickness, and concentration of polymers’, ensure obtaining desirable VH release profile for extended period of time, was defined. X composition of tablet with pellets were examined in order to obtained formulation, from which VH release would mostly appropriate pellets before compressing. Compression of pellets into tablet, being a modern technological process than enclosing them into hard gelatine capsule. The optimized batch evaluated by studied the effect of compression force, tablet hardness and friability and drug release from the pellets by sustained release manner.

Design, Preparation and In Vitro Evaluation of Core-Shell Fused Deposition Modelling 3D-Printed Verapamil Hydrochloride Pulsatile Tablets.

The aim of the study was to investigate core–shell pulsatile tablets by combining the advantages of FDM 3D printing and traditional pharmaceutical technology, which are suitable for a patient’s individual medication and chronopathology. The tablets were designed and prepared with the commercial verapamil hydrochloride tablets as core inside and the fused deposition modelling (FDM) 3D-printed shell outside. Filaments composed of hydroxypropylmethyl cellulose (HPMC) and polyethylenglycol (PEG) 400 were prepared by hot melt extrusion (HME) and used for fabrication of the shell. Seven types of printed shells were designed for the tablets by adjusting the filament composition, geometric structure and thickness of the shell. A series of evaluations were then performed on the 3D-printed core–shell tablets, including the morphology, weight, hardness, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), in vitro drug release and CT imaging. The results showed that the tablets prepared by FDM 3D printing appeared intact without any defects. All the excipients of the tablet shells were thermally stable during the extruding and printing process. The weight, hardness and in vitro drug release of the tablets were affected by the filament composition, geometric structure and thickness of the shell. The pulsatile tablets achieved personalized lag time ranging from 4 h to 8 h in the drug release test in phosphate-buffered solution (pH 6.8). Therefore, the 3D-printed core–shell pulsatile tablets in this study presented good potential in personalized administration, thereby improving the therapeutic effects of the drug for circadian rhythm disease.

In Silico and Ex Vivo Studies on the Spasmolytic Activities of Fenchone Using Isolated Guinea Pig Trachea.

Fenchone is a bicyclic monoterpene found in a variety of aromatic plants, including Foeniculum vulgare and Peumus boldus, and is used in the management of airways disorders. This study aimed to explore the bronchodilator effect of fenchone using guinea pig tracheal muscles as an ex vivo model and in silico studies. A concentration-mediated tracheal relaxant effect of fenchone was evaluated using isolated guinea pig trachea mounted in an organ bath provided with physiological conditions. Sustained contractions were achieved using low K+ (25 mM), high K+ (80 mM), and carbamylcholine (CCh; 1 µM), and fenchone inhibitory concentration–response curves (CRCs) were obtained against these contractions. Fenchone selectively inhibited with higher potency contractions evoked by low K+ compared to high K+ with resultant EC50 values of 0.62 mg/mL (0.58–0.72; n = 5) and 6.44 mg/mL (5.86–7.32; n = 5), respectively. Verapamil (VRP) inhibited both low and high K+ contractions at similar concentrations. Pre-incubation of the tracheal tissues with K+ channel blockers such as glibenclamide (Gb), 4-aminopyridine (4-AP), and tetraethylammonium (TEA) significantly shifted the inhibitory CRCs of fenchone to the right towards higher doses. Fenchone also inhibited CCh-mediated contractions at comparable potency to its effect against high K+ [6.28 mg/mL (5.88–6.42, n = 4); CCh] and [6.44 mg/mL (5.86–7.32; n = 5); high K+]. A similar pattern was obtained with papaverine (PPV), a phosphodiesterase (PDE), and Ca2+ inhibitor which inhibited both CCh and high K+ at similar concentrations [10.46 µM (9.82–11.22, n = 4); CCh] and [10.28 µM (9.18–11.36; n = 5); high K+]. However, verapamil, a standard Ca2+ channel blocker, showed selectively higher potency against high K+ compared to CCh-mediated contractions with respective EC50 values of 0.84 mg/mL (0.82–0.96; n = 5) 14.46 mg/mL (12.24–16.38, n = 4). The PDE-inhibitory action of fenchone was further confirmed when its pre-incubation at 3 and 5 mg/mL potentiated and shifted the isoprenaline inhibitory CRCs towards the left, similar to papaverine, whereas the Ca2+ inhibitory-like action of fenchone pretreated tracheal tissues were authenticated by the rightward shift of Ca2+ CRCs with suppression of maximum response, similar to verapamil, a standard Ca2+ channel blocker. Fenchone showed a spasmolytic effect in isolated trachea mediated predominantly by K+ channel activation followed by dual inhibition of PDE and Ca2+ channels. Further in silico molecular docking studies provided the insight for binding of fenchone with Ca2+ channel (−5.3 kcal/mol) and K+ channel (−5.7), which also endorsed the idea of dual inhibition.

Co-delivery of triamcinolone acetonide and verapamil for synergistic treatment of hypertrophic scars via carboxymethyl chitosan and Bletilla striata polysaccharide-based microneedles

Hypertrophic scar (HS) is a frequently diagnosed skin disease that is difficult to treat. HS is usually associated with itching and pain and causes both physical and psychological issues. In this study, a safe, convenient, and efficient therapy for HS is developed. Carboxymethyl chitosan (CMCH) and Bletilla striata polysaccharide (BSP) are used to prepare microneedles (MN) via a micro-molding method. Hydroxypropyl β-cyclodextrin (HP-β-CD) is used to encapsulate triamcinolone acetonide (TA) and the obtained inclusion is co-loaded with verapamil (VRP) to MN. The MN is then attached to an Ethyl cellulose (EC) base layer to obtain a MN patch. The MN patch has uniform needles, sufficient mechanical strength, good penetration and dissolution in skin, and low cytotoxicity. It also significantly decreases the thickness of HS, and hydroxyproline (HYP) and transforming growth factor-beta 1 (TGF-β1) expression in HS, improves collagen fiber arrangement, and reduces dermis congestion and hyperplasia.

Verapamil hydrochloride nanoparticles formulated with chitosan and sodium alginate by an ionic gelation method

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To formulate chitosan-based nanoparticles for extended release of verapamil so as to reduce its dosing frequency.&#x0D; Methods: Nanoparticles of chitosan and sodium alginate loaded with verapamil HCl were synthesized using the ionotropic gelation method. The formulations were optimized by cross linking of tripolyphosphate with chitosan, and CaCl2 with sodium alginate at different concentrations. The ionic gelation method was used to produce seven different formulations. The best formulation for nanoparticles preparation involved using 0.06 % sodium alginate with 18 mM CaCl2 and of chitosan: TPP (5:1 ratio). The compatibility of verapamil HCl with sodium alginate and chitosan was tested using FTIR.&#x0D; Results: Verapamil nanoparticles had a direct correlation with the polymer concentrations used. A 5:1 ratio of chitosan:TPP resulted in a particle size of 173 nm, and high drug entrapment. The size of verapamil nanoparticles prepared with sodium alginate was 186 nm (p = 0.02). Cross-linking agent played an important role in the preparation of the nanoparticles. Scanning electron micrographs showed that the nanoparticles were coalesced with one another, and had rough surfaces. Chitosan-based formulations had an entrapment efficiency in the range of 38.63 – 50.58 %, while the entrapment efficiency of sodium alginate-based formulations was 11.70 – 40.57 % (p 0.43).&#x0D; Conclusion: Verapamil nanoparticles have been successfully formulated by ionic gelation method using natural polymers. The nano-formulations did not exhibit polymer-drug interactions, but manifest extended drug-release profiles.&#x0D; &#x0D; &#x0D; &#x0D;

FDM 3D-Printed Sustained-Release Gastric-Floating Verapamil Hydrochloride Formulations with Cylinder, Capsule and Hemisphere Shapes, and Low Infill Percentage.

The aim of this work was to design and fabricate fused deposition modeling (FDM) 3D-printed sustained-release gastric-floating formulations with different shapes (cylinder, capsule and hemisphere) and infill percentages (0% and 15%), and to investigate the influence of shape and infill percentage on the properties of the printed formulations. Drug-loaded filaments containing HPMC, Soluplus® and verapamil hydrochloride were prepared via hot-melt extrusion (HME) and then used to print the following gastric-floating formulations: cylinder-15, capsule-0, capsule-15, hemisphere-0 and hemisphere-15. The morphology of the filaments and the printed formulations were observed by scanning electron microscopy (SEM). The physical state of the drugs in the filaments and the printed formulations were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The printed formulations were evaluated in vitro, including the weight variation, hardness, floating time, drug content and drug release. The results showed that the drug-loaded filament prepared was successful in printing the gastric floating formulations. Verapamil hydrochloride was proved thermally stable during HME and FDM, and in an amorphous state in the filament and the printed formulations. The shape and infill percentage of the printed formulations effected the hardness, floating time and in vitro drug release.

Losartan Potassium and Verapamil Hydrochloride Compound Transdermal Drug Delivery System: Formulation and Characterization

Losartan Potassium and Verapamil Hydrochloride Compound Transdermal Drug Delivery System: Formulation and Characterization

Effect of single and multilayered Ti3C2TX MXene as a catalyst and adsorbent on enhanced sonodegradation of diclofenac and verapamil

Single and multilayered Ti3C2TX MXene (referred to as SLM and MLM in this study, respectively) was applied as catalysts in the ultrasonic (US) process to treat selected pharmaceutical compounds including diclofenac and verapamil (VRP). Due to solid surface, elemental composition, and functional groups of Ti3C2TX MXene, the free OH• production was increased by 48.8% for the US treatment with SLM and 59.8% for the US treatment with MLM compared with the US-only treatment. Additionally, adsorption affected the performance during the US treatment in the presence of the catalyst. Thus, the US treatment in the presence of Ti3C2TX MXene had an enhanced performance not only because of increased oxidation but also because of adsorption, particularly between positively charged VRP and negatively charged Ti3C2TX MXene. Moreover, although the degradation of the performance was higher for SLM (85.1%) than for MLM (81.8%), by improving the dispersion and reducing the size via sonication, the US treatment in the presence of MLM showed the highest synergy effect. In other words, the US treatment in the presence of MLM showed higher performance than the simple sum of oxidation and adsorption. These findings confirm that the US treatment in the presence of MLM may be a promising technology to treat various pharmaceuticals as a more degradable, strongly reusable, and less toxic process.

Formulation &amp; Evaluation of Effervescent Tablet of Verapamil Hydrochloride

The chief aim of the present investigation is to study the Formulation &amp; Evaluation of Effervescent Tablet of Verapamil Hydrochloride. The floating tablets of verapamil hydrochloride were prepared by direct compression technique. For each tablet formulation, drug, HPMC-K15M, karaya gum, sodium bicarbonate, and diluents were blended homogeneously for 10 min followed by addition of magnesium stearate. The total weight of each tablet was 300 mg. The amount of karaya gum used was in the range of 40–90 mg, whereas HPMC was used in the range of 20-40 mg. The powder mixture was further mixed for 5 min in a mortar. The resultant mixture was compressed into tablets using a Rimek rotary tablet machine. After preparation, the formulations were evaluated by various parameters. The friability of the tablet formulation varied between 0.3 ± 0.0063 to 0.59 ± 0.0076%. The weight variation of prepared tablet formulation complies with USP limits. The thickness was found to be in the range of 4.1 ± 0.48 to 4.2 ± 0.76 mm. The assay for drug content varied between 96.53 ± 0.36 to 102.03 ± 0.52%. The B1, B5, B6, B9, and B10 exhibited more than 75% drug release at 12 h. The B1 exhibited a maximum of 30 % drug release in the 1st hour and constant release for almost up to 12 h. B8 showed the least drug release among all other formulations; this may be due to the formation of a thick gel barrier on the tablet. Tablets were prepared by direct compression. Technological characteristics of floating tablets were within the Pharmacopoeial limit. Tablets floated for more than 8 h. Complete swelling was achieved by the end of 8 h, so percent swelling was determined at the end of 8 h for all the developed formulations.

Comparison Between Saphenous Vein Graft and Radial Artery Graft in Coronary Artery Bypass Grafting

Background: To bypass the obstruction in native coronary arteries both arterial and venous grafts are used. Inspite of having radial artery graft as a favored second conduit for bypass, venous grafts are more frequently used. Objective: To compare the CT angiography patency findings of radial artery graft vs. saphenous vein graft 3 months postoperatively. Study Design: Randomized controlled trial. Settings: The study was conductedat the Department of Cardiac Surgery, Mayo Hospital, Lahore. Data Collection: All patients fulfilling theinclusioncriteria were recruited. A written informed consentwastaken. The non-dominant arm was used almostexclusively forharvesting the radial artery in those patients who have positive modified Allen`s test as a pedicle by atraumatic "no-touch" technique. After heparanization, it was immersed in diluted solution (Inj. verapamil hydrochloride 5mg + Inj. nitroglycerin 2.5mg + Inj. heparin 500 IU + Inj. ringer lactate 300 ml with Inj. 8.4% NaHCO3 0.9 m1). All the patients in the study received LIMA to LAD and were done on pump. After that the patients were dividedinto2 groups namely Group I and Group II by computer generated method. In Group I, the patient received the radial artery as a second graft to a coronary having more than 90% stenosis. The third or fourth graft if required is saphenous vein graft. The group II had SVG as second, third or fourth grafts, one of the venous grafts were to a coronary having more than 90% stenosis. Results: Average age of all (n=62) patients was 38.82±9.93 years. Average age in Group-I &amp; II patients was 39.09±9.49 &amp; 38.54±10.50 years respectively. Among patients 47% were male and 53% were female patients. In Group-I, 12 (38.7%) of the patients were male, and 19 (67.3%) were female, whereas in Group-II, 17 (54.8%) of the patients were male, and 14 (45.8%) were female. In Group-I 1(3.2%) patient and in Group-II 3(9.7%) patients died (p=0.301). Insignificant difference was seen for cardiac arrhythmias i.e. Group-I:16.1% vs. Group-II: 19.4%, p=0.740. Myocardial infarction in Group-A 5(16.1%) patients and in Group-B 7(22.6%) (p=0.520). In Group-A, 30(96.8%) patients and in Group-B, 28(90.3%) patients showed patency of artery after coronary artery bypass grafting(P&gt;0.05). Conclusion: We discovered no significant difference in the patency of both radial artery and saphenous vein grafts on 3 months postoperative CT angiography and clinical outcomes in terms of perioperative mortality, MI, and cardiac arrhythmias in patients who underwent CABG in this study. Keywords: radial artery graft, saphenous vein graft, coronary artery bypass grafting, Myocardial Infarction, Mortality, Cardiac arrhythmias

Formulation, Development and Characterization of Floating Microspheres of Selected Calcium Channel Blocker

The main aim of the present investigation is to study of formulation, development and characterization of floating mcrospheres of verapamil hydrochloride. Floating microspheres with a central hollow cavity were prepared by using a modified Quasi-emulsion diffusion technique. Weighed quantities of verapamil hydrochloride, ethyl cellulose, polyethylene oxide and hydroxy propylmethyl cellulose (HPMC K15M) were dissolved in a mixture of ethanol and dichloromethane (1:1 solvent ratio) at room temperature in a magnetic stirrer at 50 rpm for 50 min. The samples were assayed for drug content using UV spectrophotometer at 228 nm after suitable dilution. No interference was found due to the other components of floating microspheres at 228 nm. The yield was determined by weighing the microspheres and then the percentage yield was calculated with respect to the weight of the input materials, i.e., weight of verapamil and polymers used. The polymers like ethyl cellulose, eudragit L 100, polyethylene oxide and HPMC were selected for hollow microspheres preparation. These formulations contained ethyl cellulose (2%) and Polyethylene oxide (1%), HPMC K15M (1%) &amp; eudragit L100 (1%) respectively. The encapsulation efficiency ranged between 53 ± 2.2 to 89 ± 1.9%, and was observed that the encapsulation efficiency increased with increasing amount of polymers in the hollow microspheres. The sphericity factors for all formulations were in the range of 1.01 ± 0.2 to 1.29 ± 0.6 and the sphericity values of best formulations F3, F7 and F9 were 1.05±0.2, 1.07 ± 0.1 and 1.16 ± 0.1 respectively. Quassi emulsion method used for preparation of hollow microspheres was suitable for poor water soluble drugs, because the drug was soluble in the internal organic phase.

Formulation Development and Evaluation of Fast Disintegrating Sustained Release Pellets Containing Verapamil Hydrochloride Tablets by Fluidized Bed Processor

This study aimed to developed novel fast disintegrating sustained release pellets containing tablet by using Fluidized Bed processor. Verapamil HCl used as a model drug for the formulation. Fluidized bed processor was used for coating of drug and polymer on the sugar spheres. To overcome the problem of swallowing for paediatric, geriatric, psychiatric, bedridden patients, uncooperative patients or for active patients who are busy and travelling and may not access to we aim to formulate the fast-disintegrating tablet. The superdisintigrant are commonly use like cross povidone, sodium starch glycolate which disintegrate tablet rapidly. It is assumed that, after the disintegration of tablets, pellets within tablets which are reside in GIT for several hours and gradually released a drug in controlled way. Eudragit RS 30D and ethyl cellulose were used as a sustained release polymer. Coating of spheres with sustained release film is achieved by bottom spray processor of FBP. Proper pellets coating film thickness, and concentration of polymers’, ensure obtaining desirable VH release profile for extended period of time, was defined. X composition of tablet with pellets were examined in order to obtained formulation, from which VH release would mostly appropriate pellets before compressing. Compression of pellets into tablet, being a modern technological process than enclosing them into hard gelatine capsule. The optimized batch evaluated by studied the effect of compression force, tablet hardness and friability and drug release from the pellets by sustained release manner.

Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization

Chirality is a property of asymmetry which determines the pharmacokinetic and pharmacological profiles of optically active pharmaceuticals. Verapamil (VER), a calcium channel blocker phenylalkylamine derivative used in the treatment of cardio-vascular diseases, is a chiral compound, marketed as a racemate, although differences between the pharmacokinetic and pharmacological attributes of the enantiomers have been reported. The aim of our study was to develop a new chiral separation method for VER enantiomers by capillary electrophoresis (CE) using cyclodextrins (CDs) as chiral selectors (CSs). After an initial screening, using different native and derivatized CDs, at four pH levels, heptakis 2,3,6-tri-O-methyl-β-CD (TM-β-CD), a neutral derivatized CD, was identified as the optimum CS. For method optimization, a preliminary univariate approach was applied to characterize the influence of analytical parameters on the separation followed by a Box–Behnken experimental design to establish the optimal separation conditions. Chiral separation of enantiomers was achieved with a resolution of 1.58 in approximately 4 min; the migration order was R-VER followed by S-VER. The method analytical performance was evaluated in terms of precision, linearity, accuracy, and robustness (applying a Plackett–Burnam experimental design). The developed method was applied for the determination of VER enantiomers in pharmaceuticals. Finally, a computer modelling of VER–CD complexes was used to describe host–guest chiral recognition.

Electrophysiological study of the interactive role of the cannabinoid breakdown inhibitors and L-type calcium channels on granular neurons in the hippocampal dentate gyrus in rats

ABSTRACT The interaction between L-type voltage-dependent Ca2+ channels and the endocannabinoid system (eCs) in synaptic plasticity is controversial. In the present research, the impact of acute administration of URB597, as an endocannabinoid breakdown inhibitor, was evaluated after chronic injection of verapamil, as a Ca2+ channels blocker, on inducing long-term potentiation (LTP) in the rat’s hippocampal dentate gyrus (DG). Treatment of male Wistar rats was done using intraperitoneal(i.p) injection of verapamil hydrochloride (n = 8) and saline (n = 10), as the solvent of verapamil once a day within 13 days. Anesthetization was done by i.p injection of urethane and the rats were located in the stereotaxic apparatus for surgery, electrode implantation, and field potential recording. After observing a steady-state baseline response, saline or URB597 were injected (n = 9). Measurement of the population spike (PS) amplitude and slope of field excitatory postsynaptic potentials (fEPSPs) in the DG region was performed as a result of perforant pathway (PP) stimulation. Our treatments could inhibit LTP. Our results indicated that the chronic administration of verapamil produced a significant decrease in the slope of fEPSP and PS amplitude. Also, acute URB597 administration decreased the slope of fEPSP and PS amplitude compared to the saline group. Moreover, URB597 administration in combination with chronic administration of verapamil produced a greater decrease in fEPSP slope and PS amplitude than the saline group. These findings indicated that verapamil and URB597 disrupted LTP induction in the DG. Moreover, an interaction was observed between Ca2+ channels and eCs. Therefore, the eCs possibly play a selective role in synaptic plasticity.

Diterpenoids from Euphorbia glomerulans with potential reversal activities against P-glycoprotein-mediated multidrug resistance

The development of collateral sensitivity agents that are able to modulate P-glycoprotein (P-gp) is the most promising approaches to overcome multidrug resistance (MDR) in cancer. In this study, eight new diterpenoids of jatrophane and ingenane type, 1–8, and three known ones (9–11) were isolated from Euphorbia glomerulans. Their structures were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations. The MDR reversal activity evaluation of these isolates on breast cancer MCF-7/ADR cells demonstrated the four potent MDR modulators (3, 4, 5, and 9) with great chemoreversal ability and low cytotoxicity. The structure-activity relationship (SAR) analysis indicated that the presence of isobutanoyloxy group at C-8 significantly enhance reversal efficiency. Compound 5 exhibited high efficacy (EC50 = 159.5 nM) in reversing MDR resistance, being stronger than verapamil (EC50 = 302.9 nM). The MDR reversal mechanism assays revealed that 5 could promote the accumulation of Rh123 and DOX in drug-resistant cells in a certain dose-dependent manner, and inhibit P-gp transport function. In addition, the possible recognition mechanism of compound 5 and verapamil (VRP) with P-gp was predicted by molecular docking.

Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools.

The aim of this study was to gain deeper insight into the mass transport mechanisms controlling drug release from polymer-coated pellets using non-invasive analytical tools. Pellet starter cores loaded with verapamil HCl (10% loading, 45% lactose, 45% microcrystalline cellulose) were prepared by extrusion/spheronization and coated with 5% Kollicoat SR:IR 95:5 or 10% Kollicoat SR:IR 90:10. Drug release was measured from ensembles of pellets as well as from single pellets upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4. The swelling of single pellets was observed by optical microscopy, while dynamic changes in the pH in the pellet cores were monitored by fluorescence spectroscopy. Also, mathematical modeling using a mechanistically realistic theory as well as SEM and Raman imaging were applied to elucidate whether drug release mainly occurs by diffusion through the intact film coatings or whether crack formation in the film coatings plays a role. Interestingly, fluorescence spectroscopy revealed that the pH within the pellet cores substantially differed upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4, resulting in significant differences in drug solubility (verapamil being a weak base) and faster drug release at lower pH: from ensembles of pellets and single pellets. The monitoring of drug release from and the swelling of single pellets indicated that crack formation in the film coatings likely plays a major role, irrespective of the Kollicoat SR:IR ratio/coating level. This was confirmed by mathematical modeling, SEM and Raman imaging. Importantly, the latter technique allowed also for non-invasive measurements, reducing the risk of artifact creation associated with sample cutting with a scalpel.

EFFICACY OF INTRALESIONAL VERAPAMIL HYDROCHLORIDE VERSUS INTRALESIONAL TRIAMCINOLONE ACETONIDE IN HYPERTROPHIC SCARS AND KELOIDS

Background: Keloids and hypertrophic scars are dermal fibro-proliferative disorders lead to disfigurement, pain and pruritus. Their management is still challenging as there is no universally accepted treatment regimen. Corticosteroid injections, most commonly triamcinolone acetonide, continue to play a major role in the management of keloids. Verapamil is a phenylalkylamine calcium channel blocker antiarrhythmic agent that has antifibrotic effect. Objective: To compare efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids. Patients and methods: Forty Egyptian patients with keloids or hypertrophic scars were divided into two equal groups. The patients were recruited from the Dermatology outpatient clinics of Al-Zahraa University Hospital during the period from May 2016 to May 2017. Informed written consents were obtained from all patients. Group A: Intralesional Verapamil Hydrochloride. Group B: Intralesional Triamcinolone Acetonide. The efficacy of treatment was evaluated by Digital photography and Vancouver scar scale before and after treatment. Two- fine millimeter punch biopsies were taken from 5 patients of the verapamil group before and after treatment to demonstrate the histopathological changes induced by verapamil. Results: Both drugs improved total Vancouver scar scale, vascularity score and pliability score of keloid or hypertrophic scar nearly equally with no statistical significant difference. Both drugs improved height of keloid or hypertrophic scar significantly, but triamcinolone showed better improvement. Verapamil highly improved pigmentation score of keloids and hypertrophic scars, but triamcinolone showed non- significant improvement. Side effects were reported in 4 patients of triamcinolone group with no side effects in verapamil group. The histopathological examination after treatment with verapamil injection showed marked reduction of collagen deposition and alteration of the fibroblast shape (from elongated to spherical), and these changes are similar to histopathological changes which occur after corticosteroids injection. Conclusion: Verapamil was among the several therapeutic modalities, have an option for keloids and hypertrophic scars with an extremely low cost and fewer adverse effects.

Comparative efficacy of intralesional verapamil hydrochloride, triamcinolone acetonide and combination of both drug in hypertrophic scars and keloids at tertiary care center

Background: Keloids and hypertrophic scars are still a therapeutic problem. Despite numerous proposed therapies reported in the literature, the management of keloid and hypertrophic scars is still challenging as there is no universally accepted treatment regimen. Compare the efficacy intralesional verapamil hydrochloride and triamcinolone acetonide separately as well as combination of both drug in treatment of hypertrophic scars and keloids.Methods: A retrospective study was carried out at the general surgery department (plastic surgery unit) at the JNUIMSRC Jaipur, Rajasthan. Total of 150 patients (60 males and 90 females) between 18 to 60 years of age were enrolled fulfilling the inclusion criteria. They were randomly categorized in to three groups (group A, B and C), based on treatment they received viz. verapamil alone, triamcinolone alone and combination of both drugs respectively. Assessment of the scars were done prior to or on the day of the first injection and at 24 weeks after the end of injection scheme by Vancouver scar scale (VSS). The decreasing values reflected clinical improvement of the scar.Results: Better improvement observed in all four parameters: height, vascularity, pliability and pigmentation among patients receiving combination of both triamcinolone-verapamil drugs as compare to those patients receiving drugs separately either verapamil or triamcinolone alone. For parameters height, pliability and pigmentation, the improvement was found to be statistically significant (p&lt;0.05)Conclusions: Study highlights that the combined verapamil and triamcinolone therapy scheme causes remarkable scar improvement in keloid and hypertrophic scars in comparison to single drug scheme.