Ontogenic expression of acetylcholinesterase activity in trachealis of young swine

1991 ◽  
Vol 261 (4) ◽  
pp. L322-L326 ◽  
Author(s):  
T. M. Murphy ◽  
R. W. Mitchell ◽  
I. J. Phillips ◽  
A. R. Leff
Keyword(s):  
Contractile Response ◽  
Age Groups ◽  
Acetylcholinesterase Activity ◽  
Zero Order ◽  
Maximal Inhibition ◽  
Zero Order Kinetics ◽  
Contractile Forces ◽  
Ontogenic Expression ◽  
Cholinergic Contraction

Previous investigations have demonstrated that cholinergic contraction of porcine tracheal smooth muscle (TSM) decreases between the second and tenth weeks of life. In this investigation, we hypothesized that the greater contractile response to acetylcholine (ACh) in TSM of 2-wk-old swine (2ws) vs. 10-wk-old swine (10ws) was the result of a relative decrease in activity of acetylcholinesterase (AChase). To examine this hypothesis, we assessed AChase activity directly in homogenates of TSM from eight 2ws and seven 10ws using a newly adapted method that measures the rate of cleavage of acetylthiocholine; enzyme activity was expressed as absorbance units per minute per milligram protein. The AChase from tissues of both age groups saturated at approximately 3 mM substrate. However, maximal AChase activity (Vmax) was significantly greater in 10ws than 2ws. Eadie-Hofstee analysis of enzyme kinetics revealed similar Michaelis-Menten constants for 2ws and 10ws. The concentration of physostigmine (PS), an inhibitor of cholinesterase, that elicited half-maximal inhibition of AChase activity also was similar for 2ws and 10ws. In separate studies, contraction of TSM strips was assessed in vitro at optimal resting length and expressed as a function of maximal force generation to potassium chloride. Strips of TSM from 2ws contracted with greater force than those of 10ws. After pretreatment with 10(-8) M PS, contractile forces were similar in 2ws and 10ws. We conclude that AChase activity measured directly in muscle homogenates is significantly reduced in TSM of 2ws vs. 10ws and that this may result in augmented contraction to ACh under conditions of zero-order kinetics.

scholarly journals Design and Evaluation of Polymeric Controlled Release Natamycin Ocular Inserts

1970 ◽  
Vol 6 (1) ◽  
pp. 108-115 ◽  
Author(s):  
A Rajasekaran ◽  
V Sivakumar ◽  
K Karthika ◽  
J Padma Preetha ◽  
T Abirami
Keyword(s):  
Drug Release ◽  
Transmission Rate ◽  
In Vitro Release ◽  
Zero Order ◽  
Release Kinetic ◽  
Permeable Membrane ◽  
Zero Order Kinetics ◽  
Zero Order Release ◽  
S 100

The main aim of this study is to develop ocular drug delivery system for Natamycin; a polyeneantibiotic is highly useful for the treatment of conjunctivitis and keratitis. The ocuserts were preparedusing different polymers such as eudragit L-100, eudragit S-100, eudragit RL-100, hydroxy propylmethyl cellulose phthalate and cellulose acetate phthalate at various proportion and combinationsusing PEG-400 as plasticizer. The prepared ocuserts were evaluated for their physicochemicalparameters like drug content, weight uniformity, folding endurance, thickness, % moistureabsorption and water vapour transmission rate. The in vitro drug release from the formulations wasstudied using commercial semi permeable membrane and the in vitro release kinetic datas weretreated according to the diffusion models proposed by Higuchi and Peppas in order to access themechanism of drug release from the formulations, which were following zero order kinetics. All theformulations showed no change in the physical appearance and the FTIR studies indicated nopossibility of interaction between drug and polymer. The expected zero order release for one day wasobserved in the formulation D1 (3% Eudragit RL100 and 1% Eudragit L100)Keywords: Ocular Insert; Ocular Delivery; NatamycinDOI: 10.3126/kuset.v6i1.3318 Kathmandu University Journal of Science, Engineering and Technology Vol.6(1) 2010, pp108-115

scholarly journals Design and Characterization of Mucoadhesive Microspheres of Etodolac

2019 ◽  
Vol 11 (03) ◽  
Author(s):  
A R Shabaraya ◽  
A S Parulkar ◽  
D Shripathy ◽  
P Shetty
Keyword(s):  
Drug Targeting ◽  
Entrapment Efficiency ◽  
Specific Region ◽  
Zero Order ◽  
Solvent Evaporation Method ◽  
In Vitro Drug Release ◽  
Zero Order Kinetics ◽  
Central Composite

Mucoadhesive microspheres are drug delivery system intended for drug targeting to a specific region. Etodolac is a Non-steroidal anti-inflammatory drug. Sustain released Etodolac loaded mucoadhesive microspheres were prepared to overcome the relatively short residence time of Etodolac in the GIT tract before elimination. Solvent evaporation method was used for preparation of mucoadhesive microspheres with the help of Carbopol 974P, HPMC K100M and HPMC K4M as the polymers. Central composite design was selected for the development of the formulation. The formulations were evaluated for their particle size, surface morphology, degree of swelling, entrapment efficiency, drug content and in-vitro drug release study was done. Based on the results obtained from the preliminary formulations three optimized formulations were designed. The percentage mucoadhesion and swelling index of these formulations were obtained in the range of 66-70% and 82.50-83.84% respectively. Optimized formulation releases 90.94% to 92.11% of drug after 10 hours and follows zero order kinetics.

scholarly journals The Study of Release of Chlorhexidine from Preparations with Modified Thermosensitive Poly-N-isopropylacrylamide Microspheres

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Witold Musial ◽  
Bojana Voncina ◽  
Janusz Pluta ◽  
Vanja Kokol
Keyword(s):  
Functional Groups ◽  
Inhibitory Concentration ◽  
Zero Order ◽  
Volume Phase Transition ◽  
Release Rates ◽  
Zero Order Kinetics ◽  
Polymeric Beads ◽  
Time Periods ◽  
Anionic Groups

The aim of this study was to investigate and compare the release rates of chlorhexidine (CX) base entrapped in the polymeric beads of modified poly-N-isopropylacrylamides (pNIPAMs) at temperatures below and over the volume phase transition temperature (VPTT) of synthesized polymers: pNIPAM-A with terminal anionic groups resulting from potassium persulfate initiator, pNIPAM-B with cationic amidine terminal groups, and pNIPAM-C comprising anionic terminals, but with increased hydrophobicity maintained by the N-tert-butyl functional groups. The preparations, assessed in vitro below the VPTT, release an initial burst of CX at different time periods between 120 and 240 min, followed by a period of 24 h, when the rate of release remains approximately constant, approaching the zero-order kinetics; the release rates for the polymers beads are as follows: pNIPAM-C>pNIPAM-B>pNIPAM-A. The pattern of release rates at temperature over the VPTT is as follows: pNIPAM-C>pNIPAM-A>pNIPAM-B. In the presence of pNIPAM-C, the duration between the start of the release and the attained minimal inhibitory concentration (MIC) for most of the microbes, in conditions over the VPTT, increased from 60 to 90 min. The release prolongation could be ascribed to some interactions between the practically insoluble CX particle and the hydrophobic functional groups of the polymer.

scholarly journals Formulation and in vitro Evaluation of Piroxicam Emulgel

2018 ◽  
Vol 10 (4) ◽  
Author(s):  
Y Bindu Vani ◽  
C. Surya Prakash Reddy
Keyword(s):  
Drug Release ◽  
Xanthan Gum ◽  
Evaluation Studies ◽  
Tween 80 ◽  
Zero Order ◽  
In Vitro Drug Release ◽  
Zero Order Kinetics ◽  
Release Studies ◽  
Span 80

The present work is concerned with the formulation and evaluation of Piroxicam emulgel employing carbopol 934 and xanthan gum as polymers. The emulgel is prepared by combining the gel and emulsion. The gel in formulations were prepared by dispersing Carbopol 934 and xanthan gum separately in purified water with constant stirring at a moderate speed and then the pH was adjusted to 4 to 5.4 using Tri-ethanol amine (TEA). The oil phase in the emulsion consists of oleic acid and span-80. The aqueous phase in the emulsion was prepared using Tween-80, propylene glycol and distilled water. The prepared emulgel formulations were subjected to evaluation studies like Physical appearance, rheological studies, estimation of drug content and in-vitro drug release. The appearance of prepared emulgel was white. The pH of the emulgel was found to be 5.4. The in vitro drug release studies revealed that formulation F1 showed 85.20% and formulation F2 showed 79.23% of drug release at the end of 8 hrs. The drug release of F1 formulation follows zero order kinetics.

scholarly journals Comparison of In-Vitro Dissolution of Griseofulvin Tablet made from Nano Particles and Solid Dispersion

2020 ◽  
Vol 8 (1) ◽  
pp. 11-13
Author(s):  
Nurul Karima ◽  
Sumaiyah Sumaiyah ◽  
Azizah Nasution
Keyword(s):  
Solid Dispersions ◽  
Zero Order ◽  
Nano Particles ◽  
In Vitro Dissolution ◽  
Active Ingredients ◽  
Zero Order Kinetics ◽  
Different Types ◽  
Active Nanoparticles ◽  
Kinetics Of

Objectives: To find out the comparison of dissolution results of griseofulvin tablets made from nanoparticles, solid dispersions, and conventional materials. Interventions: Different types of active ingredients in the form of nanoparticles and solid dispersions can affect the dissolution results of tablets. Main outcomes measure: The results obtained in this study are the cumulative dissolution percentage and the order kinetics of the release of active ingredients. Conclusion: There was no significant cumulative percent drug release difference (p> 0.05) between nano particles, solid dispersions, and conventional materials. Tablets containing active nanoparticles, solid dispersions, and conventional materials show a linear relationship with a correlation coefficient (R2) close to 1, shown in zero-order kinetics models.    

scholarly journals The influence of hydrophylic polymers on the release rate of calcium dobesilate in hydrogel formulation assessed in vitro using porcine ear skin

2015 ◽  
Vol 28 (4) ◽  
pp. 225-230 ◽  
Author(s):  
Dorota Wojcik-Pastuszka ◽  
Anna Lisik ◽  
Maria Twarda ◽  
Ryszard Berkowski ◽  
Witold Musial
Keyword(s):  
Release Rate ◽  
Hydroxypropyl Methylcellulose ◽  
Zero Order ◽  
Kinetics Model ◽  
Calcium Dobesilate ◽  
First Order ◽  
Anionic Polymers ◽  
First Order Kinetics ◽  
Zero Order Kinetics

Abstract A shortage of available experimental data exists in the available bibliography on the release rate of calcium dobesilate (CD) from hydrogel formulations. Thus, the aim of the study was to evaluate the effect of selected hydrophilic nonionic polymers and anionic polymers on the release rate of CD from formulation provided for dermal application, as compared to the reference product in the market. The work utilized excised pork skin, while, Methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), and anionic polymers (copolymers of acrylic acid) were used as CD carriers. The release study was executed by the pharmacopoeial paddle method, with extraction cells and fresh excised porcine skin as a membrane. CD in aqueous acceptor fluid was quantified by UV-VIS spectrometry at 300 nm. Subsequently, the kinetic curves were fitted to a zero-order kinetics model, a first-order kinetics model, a second-order kinetics model, as well as to the Higuchi model. The work saw that porcine ear skin influences the release pattern of the CD, compared to the artificial membrane. In the study, the evaluated formulations with MC, polyacrylic acid (PA) and polyacrylate crosspolymer 11 (PC-11) deliver over 60% of the active component (AC), within 250 min, through the excised porcine ear skin, to the acceptor compartment. Moreover, the release observed via porcine ear skin to the aqueous acceptor compartment is congenial to zero-order or first-order kinetics. In addition, the formulations prepared on the basis of MC and PA appear to control AC delivery, independently of actual concentration of AC.

Acetylcholinesterase Inhibitory Potential and Antioxidant Activities of Five Cultivars of Rosa Damascena Mill. From Isparta, Turkey

2020 ◽  
Vol 18 (4) ◽  
pp. 354-359
Author(s):  
Shirin Tarbiat ◽  
Azize Simay Türütoğlu ◽  
Merve Ekingen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radical ◽  
Neurodegenerative Disorder ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Acetylcholinesterase Activity ◽  
Rosa Damascena ◽  
Free Radical Damage

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impairment of language. Alzheimer's disease is strongly associated with oxidative stress and impairment in the cholinergic pathway, which results in decreased levels of acetylcholine in certain areas of the brain. Hence, inhibition of acetylcholinesterase activity has been recognized as an acceptable treatment against Alzheimer's disease. Nature provides an array of bioactive compounds, which may protect against free radical damage and inhibit acetylcholinesterase activity. This study compares the in vitro antioxidant and anticholinesterase activities of hydroalcoholic extracts of five cultivars of Rosa Damascena Mill. petals (R. damascena 'Bulgarica', R. damascena 'Faik', R. damascena 'Iranica', R. damascena 'Complex-635' and R. damascena 'Complex-637') from Isparta, Turkey. The antioxidant activities of the hydroalcoholic extracts were tested for ferric ion reduction and DPPH radical scavenging activities. The anti-acetylcholinesterase activity was also evaluated. All rose cultivars showed a high potency for scavenging free radical and inhibiting acetylcholinesterase activity. There was a significant correlation between antioxidant and acetylcholinesterase inhibitory activity. Among cultivars, Complex-635 showed the highest inhibitory effect with an IC50 value of 3.92 µg/mL. Our results suggest that all these extracts may have the potential to treat Alzheimer's disease with Complex-635 showing more promise.

Gastroretentive Floating Capsules of Risedronate Sodium: Development, Optimization, in vitro and in vivo Evaluation in Healthy Human Volunteers

2015 ◽  
Vol 8 (2) ◽  
pp. 2835-2842
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Arun Kumar Jarathi ◽  
Suresh Gande ◽  
Viswaja Medipally ◽  
Ramesh Bomma
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Zero Order ◽  
Wet Granulation ◽  
Capsule Formulation ◽  
In Vivo Evaluation ◽  
Healthy Human ◽  
X Ray ◽  
Human Volunteers

Background and the purpose of the study: Risedronate sodium inhibits osteoclast bone resorption and modulates bone metabolism. Risedronate has a high affinity for hydroxyapatite crystals in bone and is a potent antiresorptive agent. In the present investigation efforts were made to improve the bioavailability of risedronate sodium by increasing the residence time of the drug through sustained-release matrix capsule formulation via gastroretentive mechanism. Capsules were prepared by wet granulation technique. The influence of gel forming agents, amount of risedronate and total weight of capsules on physical properties, in vitro buoyancy, drug release, FTIR, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study at 40 °C/75% RH, 25 °C/60% RH for the period of three months. For all formulations, kinetics of drug release from capsules followed Higuchi’s square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulation containing 25 mg HPMC K4M and 75 mg HPMC K100 LV (F-8) showed zero order release profile. There was no significant change in the selected formulation, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.60 ± 0.77 hrs for the selected formulation. Stable, sustained release effervescent floating capsules of risedronate sodium could be prepared by wet granulation technique.  

Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

2019 ◽  
Vol 15 (4) ◽  
pp. 373-382 ◽  
Author(s):  
Ralph C. Gomes ◽  
Renata P. Sakata ◽  
Wanda P. Almeida ◽  
Fernando Coelho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Population Aging ◽  
Acetylcholinesterase Inhibitors ◽  
Acetylcholinesterase Activity ◽  
Docking Study ◽  
Biological Properties ◽  
Ache Inhibitor ◽  
Molecular Docking Study

Background: The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease. Methods: The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase. Results: Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Conclusion: We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.

Formulation Development and Characterization of controlled release core in cup matrix tablets of venlafaxine HCl

2020 ◽  
Vol 15 ◽  
Author(s):  
Balaji Maddiboyina ◽  
Vikas Jhawat ◽  
Gandhi Sivaraman ◽  
Om Prakash Sunnapu ◽  
Ramya Krishna Nakkala ◽  
...  
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Release Rate ◽  
Zero Order ◽  
Water Soluble ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Crystalline Cellulose ◽  
Hydrophobic Polymers

Background: Venlafaxine HCl is a selective serotonin reuptake inhibitor which is given in the treatment of depression. The delivery of the drug at a controlled rate can be of great importance for prolonged effect. Objective: The objective was to prepare and optimize the controlled release core in cup matrix tablet of venlafaxine HCl using the combination of hydrophilic and hydrophobic polymers to prolong the effect with rate controlled drug release. Methods: The controlled release core in cup matrix tablets of venlafaxine HCl were prepared using HPMC K5, K4, K15, HCO, IPA, aerosol, magnesium sterate, hydrogenated castor oil and micro crystalline cellulose PVOK-900 using wet granulation technique. Total ten formulations with varying concentrations of polymers were prepared and evaluated for different physicochemical parameters such FTIR analysis for drug identification, In-vitro drug dissolution study was performed to evaluate the amount of drug release in 24 hrs, drug release kinetics study was performed to fit the data in zero order, first order, Hixson–crowell and Higuchi equation to determine the mechanism of drug release and stability studies for 3 months as observed. Results: The results of hardness, thickness, weight variation, friability and drug content study were in acceptable range for all formulations. Based on the In vitro dissolution profile, formulation F-9 was considered to be the optimized extending the release of 98.32% of drug up to 24 hrs. The data fitting study showed that the optimized formulation followed the zero order release rate kinetics and also compared with innovator product (flavix XR) showed better drug release profile. Conclusion: The core-in-cup technology has a potential to control the release rate of freely water soluble drugs for single administration per day by optimization with combined use of hydrophilic and hydrophobic polymers.

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