Biopharmaceutical and rheometric studies in the development of a gel composition with dimethindene maleate

Every year there is an increase in the number of cases of hypersensitivity to bites from various insects. A local allergic reaction to bites occurs within a few minutes and is accompanied by acute pain at the site of the bite, severe itching, hyperemia, the appearance of papules, tissue edema, and sometimes a small-point rash around. Considering the small number of drugs for local therapy of allergic manifestations and the unidirectional nature of their action, it is urgent to develop a drug containing the antihistamine dimethindene maleate and dexpanthenol, which plays the role of an anti-inflammatory, reparative and dermatoprotective substance. The aim. The aim of the study is to substantiate the delivery system of dimethindene maleate and dexpanthenol based on biopharmaceutical and rheometric research methods. Materials and methods. To determine the component composition of the active ingredient delivery system, the type of dimetindene maleate administration was substantiated by studying its solubility. As a delivery system for active pharmaceutical ingredients, hydrogels were considered, which were made using high-molecular compounds of various origins: a natural substance – xanthan gum, a semi-synthetic substance – gyroxypropyl methylcellulose, and a synthetic substance – carbomer. The rate of release of dimethindene maleate from hydrogels was estimated by studying the kinetics of release through a semipermeable membrane. The assessment of the viscoelastic properties of hydrogels was carried out by performing an oscillatory rheometry test, which makes it possible to quantitatively determine the viscous and elastic components, as well as to characterize the bioadhesive properties. Results. Based on the results of studying the solubility of dimethindene maleate in hydrophilic non-aqueous solvents, it was determined that propylene glycol is optimal for ensuring the introduction of a substance into hydrogel bases as a solution. As a result of studying the kinetics of the release of dimethindene maleate from hydrogels, it was found that the use of carbomer as a delivery system provides the release of 28.33 % of dimethindene maleate, xanthan gum – 25 %, hydroxypropyl methylcellulose – 7.33 %. When studying the viscoelastic properties by determining the values of the storage modulus G', the loss modulus G" and the damping (attenuation) factor tg δ, it was found that the carbomer-based hydrogel is a viscoelastic solid, the xanthan gum and hydroxypropyl methylcellulose-based hydrogels are a viscoelastic liquid. Bioadhesion on the surface of the skin during use has the advantage of carbomer hydrogel. Conclusions. Based on the combination of biopharmaceutical and rheometric methods for substantiating the composition of the delivery system for dimetindene maleate and dexpanthenol, it is rational to use carbomer for further pharmacological and microbiological studies

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Comparative study of blood coagulation kinetics and thrombus formation by rheological and electrorheological methods.

Тромбоз, гемостаз и реология ◽

10.25555/thr.2020.4.0951 ◽

2020 ◽

Author(s):

Н.М. Антонова ◽

И.М. Иванов ◽

У.Б. Виндбергер ◽

В.К. Паскова

Keyword(s):

Elastic Modulus ◽

Electric Field ◽

Storage Modulus ◽

Whole Blood ◽

Viscoelastic Properties ◽

Loss Modulus ◽

Thrombus Formation ◽

Kinetics Of ◽

Low Shear

Цель исследования: изучить механизмы формирования и тромбодинамические свойства кровяного сгустка при тромбообразовании in vitro и представить сравнительное исследование кинетики тромбообразования с помощью реологических и электрореологических методов в условиях постоянного и осциллирующего сдвигового вискозиметрического течения; оценить свертывание цельной и консервированной крови, ее вязкоупругие свой ства и влияние фибриногена и декстранов на формирование сгустка. Материалы и методы. Вязкость и удельную электропроводимость нормальной и консервированной с CPD-A1-адениновым раствором крови измеряли ротационным вискозиметром Low Shear 30 Contraves (LS30) с коаксиальными цилиндрами и копией измерительной системы MS1/1 со встроенными электродами (разработана на базе LS30) в условиях постоянного сдвигового потока и в электрическом поле. Вязкоупругие свойства нормальной цельной крови исследовали с помощью реометра Physica MCR 301 (Anton Paar, Austria) в условиях осциллирующего синусоидального потока. Результаты. Представлены результаты кинетики динамической вязкости и удельной электропроводимости консервированной крови в процессе коагуляции в условиях постоянного сдвигового потока и в электрическом поле. Исследованы вязкоупругие свойства цельной крови в условиях синусоидального осциллирующего вискозиметрического течения и представлены зависимости упругого модуля G' (storage modulus) и модуля потерь G'' (loss modulus), а также нормальных сил как функция времени при свертывании. Приводятся данные эффекта фибриногена и декстрана на упругий модуль G' и на модуль потерь G'' цельной крови в процессе коагуляции. Заключение. В условиях вискозиметрического течения при низких скоростях сдвига кинетика тромбообразования характеризуется начальным этапом постепенного увеличения кажущейся вязкости и уменьшения удельной электропроводимости крови и периодом интенсивной коагуляции, характеризирующимся экспоненциальным ростом вязкости и параллельным уменьшением удельной электропроводимости исследуемого образца. Установлено, что коагулирующая цельная кровь обладает нелинейными вязкоупругими свойствами. Кинетика образования сгустка в условиях осциллирующего вискозиметрического течения крови характеризуется увеличением упругого модуля G' и модуля потерь G'' со временем. Одновременно зарегистрирована и отрицательная нормальная сила исследуемого образца в зазоре между пластинами при постоянной толщине зазора. Повышение содержание фибриногена ускоряет коагуляцию и увеличивает значения упругого модуля G' и модуля потерь G'', а также и нормальной силы коагулирующей цельной крови. Objectives: to study the mechanisms of thrombus formation and thrombodynamic properties of a blood clot during coagulation in vitro and to present a comparative study of clot kinetics formation under conditions of steady and oscillating shear viscometric flow and at electric field by rheological and electrorheological methods; to evaluate the coagulation of whole and preserved blood, its viscoelastic properties and the effect of fi brinogen and dextrans on clot formation. Materials/ Methods. The viscosity and electrical conductivity of normal blood and blood preserved with CPD-A1-adenine solution were measured with a Low Shear 30 Contraves (LS30) rotational viscometer with coaxial cylinders and with a copy of the measuring system MS1 / 1 with builtin electrodes at a steady viscometric shear flow and in an electric field too. The viscoelastic properties of normal whole blood were investigated using a Physica MCR 301 rheometer (Anton Paar, Austria) at an oscillating sinusoidal flow. Results. Kinetics of the dynamic viscosity and electrical conductivity of preserved blood during coagulation at a steady shear flow and at electric field were obtained. The viscoelastic properties of whole blood were investigated under conditions of sinusoidal oscillating viscometric flow. The dependences of the elastic (storage) modulus G' and the loss modulus G'', as well as the normal coagulation forces as a function of time are presented. The effect of fibrinogen and dextran on the elastic modulus G' and the loss modulus G'' of whole blood during coagulation are presented. Conclusions. The kinetics of blood coagulation at low shear rates is characterized by a gradual increase of the apparent viscosity and a decrease in blood conductivity at the initial stage and an exponential increase in viscosity during intensive coagulation and a parallel decrease of conductivity too. It was established that coagulating whole blood exhibit nonlinear viscoelastic properties under conditions of sinusoidal blood flow. The kinetics of thrombus formation is characterized by increasing the elastic modulus G' (storage modulus) and the loss modulus G'' with time. The negative normal force in the gap between the plates is also registered at a constant thickness of the gap. An increase in fibrinogen content accelerates coagulation and increases the values of elastic modulus G' and loss modulus G', as well as of the normal force of coagulating whole blood.

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Formulation and Optimization of Sodium Alginate Polymer Film as a Buccal Mucoadhesive Drug Delivery System Containing Cetirizine Dihydrochloride

Pharmaceutics ◽

10.3390/pharmaceutics13050619 ◽

2021 ◽

Vol 13 (5) ◽

pp. 619

Author(s):

Krisztián Pamlényi ◽

Katalin Kristó ◽

Orsolya Jójárt-Laczkovich ◽

Géza Regdon

Keyword(s):

Drug Delivery ◽

Tensile Strength ◽

Sodium Alginate ◽

Drug Delivery System ◽

Delivery System ◽

Polymer Films ◽

Hydroxypropyl Methylcellulose ◽

Chemical Properties ◽

Active Pharmaceutical Ingredient ◽

Swallowing Problems

Currently, pharmaceutical companies are working on innovative methods, processes and products. Oral mucoadhesive systems, such as tablets, gels, and polymer films, are among these possible products. Oral mucoadhesive systems possess many advantages, including the possibility to be applied in swallowing problems. The present study focused on formulating buccal mucoadhesive polymer films and investigating the physical and physical–chemical properties of films. Sodium alginate (SA) and hydroxypropyl methylcellulose (HPMC) were used as film-forming agents, glycerol (GLY) was added as a plasticizer, and cetirizine dihydrochloride (CTZ) was used as an active pharmaceutical ingredient (API). The polymer films were prepared at room temperature with the solvent casting method by mixed two-level and three-level factorial designs. The thickness, tensile strength (hardness), mucoadhesivity, surface free energy (SFE), FTIR, and Raman spectra, as well as the dissolution of the prepared films, were investigated. The investigations showed that GLY can reduce the mucoadhesivity of films, and CTZ can increase the tensile strength of films. The distribution of CTZ proved to be homogeneous in the films. The API could dissolve completely from all the films. We can conclude that polymer films with 1% and 3% GLY concentrations are appropriate to be formulated for application on the buccal mucosa as a drug delivery system.

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Rheological and Textural Properties of Apple Pectin-Based Composite Formula with Xanthan Gum Modification for Preparation of Thickened Matrices with Dysphagia-Friendly Potential

Polymers ◽

10.3390/polym13060873 ◽

2021 ◽

Vol 13 (6) ◽

pp. 873

Author(s):

Huaiwen Yang ◽

Chai-Chun Tsai ◽

Jung-Shiun Jiang ◽

Chi-Chung Hua

Keyword(s):

Storage Modulus ◽

Water Consumption ◽

Xanthan Gum ◽

Loss Modulus ◽

Textural Properties ◽

Apple Pectin ◽

Composite Matrix ◽

Low Concentrations ◽

Composite Formula

Modifying the consistency of a given edible fluid matrix by incorporating food thickeners is a common nursing remedy for individuals with dysphagia when adequate water consumption is a concern. As apple pectin (AP) offers nutraceutical benefits, properly formulated apple pectin (AP)-based thickeners featuring xanthan gum (XG) can be superior candidates for preparation of dysphagia-friendly matrices (DFMs). Our recruited DFMs exhibit fluid-like behavior (loss modulus > storage modulus, G” > G’) at lower AP concentrations (2 and 5%, w/w); they turn into weak/critical gels (G’ ≈ G”) as the concentration becomes higher (9%). In contrast, XG-DFMs display gel-like attributes with G’ > G”, even at rather low concentrations (<1%) and become more resistant to sugar, Na+, and Ca2+ modifications. The composite matrix of AP1.8XG0.2 (constraint at 2%) exhibits a confined viscosity of 278 ± 11.7 mPa∙s, which is considered a DFM, in comparison to only AP- or XG-thickened ones. The hardness measurements of XG0.6 and AP1.2XG0.8 are 288.33 ± 7.506 and 302.00 ± 9.849 N/m2, respectively, which potentially represent a promising formulation base for future applications with DFMs; these textural values are not significantly different from a commercially available product (p > 0.05) for dysphagia nursing administrations.

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DESIGN AND EVALUATION OF INTRAGASTRIC BUOYANT TABLETS OF VENLAFAXINE HYDROCHLORIDE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i5.16948 ◽

2017 ◽

Vol 10 (5) ◽

pp. 166

Author(s):

Parasuram Rajam Radhika ◽

Nishala N ◽

Kiruthika M ◽

Sree Iswarya S

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Xanthan Gum ◽

Hydroxypropyl Methylcellulose ◽

Methyl Cellulose ◽

In Vitro Drug Release ◽

Weight Variation ◽

Floating Drug Delivery ◽

Venlafaxine Hydrochloride

Objective: The present study was undertaken to prolong the release of orally administered drug. The aim is to formulate, develop, and evaluate theintragastric buoyant tablets of venlafaxine hydrochloride, which releases the drug in a sustained manner over a period of 12 hrs. Different formulationswere formulated using the polymers Carbopol 934 P, xanthan gum, hydroxypropyl methylcellulose (HPMC K100M) with varying concentration ofdrug: Polymer ratio of 1:1, 1:1.5, 1:2, in which sodium bicarbonate acts as gas generating agent, and microcrystalline cellulose as a diluent.Methods: The tablets were prepared by direct compression and evaluated for tablet thickness, weight variation, tablet hardness, friability, in vitrobuoyancy test, in vitro drug release and Fourier transform infrared spectroscopy. Formulations were evaluated by floating time, floating lag time and in vitro drug release. Dissolution profiles were subjected for various kinetic treatments to analyze the release pattern of drug.Results: It was found that drug release depends on swelling, erosion, and diffusion, thus following the non-Fickian/anomalous type of diffusion.Formulation F8 was considered as an optimized formulation for gastro retentive floating tablet of venlafaxine hydrochloride. The optimizedformulation showed sustained drug release and remained buoyant on the surface of the medium for more than 12 hrs. As the concentration of HPMCK100M increases in the formulation the drug release rate was found to be decreased. The optimized formulation was subjected for the stability studiesand was found to be stable as no significant change was observed in various evaluated parameters of the formulation.Conclusion: It can be concluded that floating drug delivery system of venlafaxine hydrochloride can be successfully formulated as an approach toincrease gastric residence time, thereby improving its bioavailability.Keywords: Venlafaxine hydrochloride, Intragastric buoyant, Floating drug delivery systems, Hydroxypropyl methyl cellulose K100M, Carbopol 934 P,Xanthan gum.

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Interactions of WPI and Xanthan in Microstructure and Rheological Properties of Gels and Emulsions

International Journal of Food Engineering ◽

10.2202/1556-3758.1104 ◽

2007 ◽

Vol 3 (4) ◽

Cited By ~ 5

Author(s):

Kooshan Nayebzadeh ◽

Jianshe Chen ◽

SM Mohammad Mousavi

Keyword(s):

Phase Separation ◽

Whey Protein ◽

Viscoelastic Properties ◽

Xanthan Gum ◽

Laser Scanning ◽

Structural Changes ◽

Spherical Shape ◽

Laser Scanning Microscopy ◽

Concentration Addition ◽

Confocal Laser

The effect of addition of xanthan gum (0.05, 0.1, 0.15, 0.25% weight/volume) on the formation and rheology of whey protein isolate (WPI)-xanthan gum gels has been investigated at neutral pH. The elastic modulus (G') values of the gelling test were compared. Low concentration of xanthan added (<0.05%,w/v) has a synergistic effect on the gel strength depend on phase separation, so that whey proteins concentrated in their phase and finally mixed gels with xanthan would be stronger than WPI gels. At higher xanthan concentration (> 0.05%, w/v), antagonist effect was observed by reducing the connection between clusters of whey protein by xanthan, so aggregation disruption and a related decrease in (G'). The phase separation microstructure of WPI-stabilized emulsion containing xanthan gum added has been investigated by rheology and confocal laser scanning microscopy. Xanthan was stained with Fluorescein 5(6)-isothiocyanate (FITC). Low xanthan concentration addition lead to depletion flocculation and increasing the xanthan concentration cause to increase the viscoelasticity of aqueous phase, so retarded macroscopic phase separation over period investigated. Structural changes in emulsion were observed in viscoelastic properties of separated phase in the rheometer. The CLSM image shows different phase which have different viscoelastic properties; xanthan-rich region transforms into the spherical shape which has the lowest interfacial energy and gradually two separated ultimately.

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Properties of Mouse Cutaneous Rapidly Adapting Afferents: Relationship to Skin Viscoelasticity

Journal of Neurophysiology ◽

10.1152/jn.01033.2003 ◽

2004 ◽

Vol 92 (2) ◽

pp. 1236-1240 ◽

Cited By ~ 3

Author(s):

P. Grigg ◽

D. R. Robichaud ◽

Z. Del Prete

Keyword(s):

Viscoelastic Material ◽

Material Properties ◽

Viscoelastic Properties ◽

Mechanical Response ◽

Loss Modulus ◽

Multiple Logistic Regression Analysis ◽

Rate Of Change ◽

Volterra Model ◽

Lower Sensitivity ◽

Dynamic Stimuli

When skin is stretched, stimuli experienced by a cutaneous mechanoreceptor neuron are transmitted to the nerve ending through the skin. In these experiments, we tested the hypothesis that the viscoelastic response of the skin influences the dynamic response of cutaneous rapidly adapting (RA) neurons. Cutaneous RA afferent neurons were recorded in 3 species of mice (Tsk, Pallid, and C57BL6) whose skin has different viscoelastic properties. Isolated samples of skin and nerve were stimulated mechanically with a dynamic stretch stimulus, which followed a pseudo Gaussian waveform with a bandwidth of 0–60 Hz. The mechanical response of the skin was measured as were responses of single RA cutaneous mechanoreceptor neurons. For each neuron, the strength of association between spike responses and the dynamic and static components of stimuli were determined with multiple logistic regression analysis. The viscoelastic material properties of each skin sample were determined indirectly, by creating a nonlinear (Wiener–Volterra) model of the stress–strain relationship, and using the model to predict the complex compliance (i.e., the viscoelastic material properties). The dynamic sensitivity of RA mechanoreceptor neurons in mouse hairy skin was weakly related to the viscoelastic properties of the skin. Loss modulus and phase angle were lower (indicating a decreased viscous component of response) in Tsk and Pallid than in C57BL6 mice. However, RA mechanoreceptor neurons in Tsk and Pallid skin did not differ from those in C57 skin with regard to their sensitivity to the rate of change of stress or to the rate of change of incremental strain energy. They did have a decreased sensitivity to the rate of change of tensile strain. Thus the skin samples with lower dynamic mechanical response contained neurons with a somewhat lower sensitivity to dynamic stimuli.

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Effect of Hydroxypropyl Methylcellulose and Ethyl Cellulose Content on Release Profile and Kinetics of Diltiazem HCl from Matrices

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v8i5.48086 ◽

2009 ◽

Vol 8 (5) ◽

Cited By ~ 11

Author(s):

R Enayatifard ◽

M Saeedi ◽

J Akbari ◽

Y H Tabatabaee

Keyword(s):

Ethyl Cellulose ◽

Hydroxypropyl Methylcellulose ◽

Release Profile ◽

Cellulose Content ◽

Diltiazem Hcl ◽

Kinetics Of

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FORMULATION AND EVALUATION OF SIMVASTATIN GASTRORETENTIVE DRUG DELIVERY SYSTEM

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2017v9i3.18763 ◽

2017 ◽

Vol 9 (3) ◽

pp. 55

Author(s):

Manjunath P. N. ◽

Satish C. S. ◽

Vasanti S. ◽

Preetham A. C. ◽

Naidu Ras

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Release Rate ◽

Drug Transport ◽

Hydroxypropyl Methylcellulose ◽

In Vitro Dissolution ◽

Dissolution Studies ◽

Viscosity Grade

Objective: The aim of this study was to formulate and evaluate gastro retentive drug delivery system (GRRDS) using an effervescent approach for simvastatin.Methods: Floating tablets were prepared using directly compressible polymers hydroxypropyl methylcellulose (HPMC) K100M, HPMC K4M and carboxymethylcellulose sodium (NaCMC). The prepared tablets were subjected to pre-formulation studies like Compressibility index, Hausner ratio and post compression parameters like buoyancy/floating test and In vitro dissolution study.Results: Drug-excipient compatibility studies performed with the help of FTIR instrument indicated that there were no interactions. The DSC thermogram of the formulations revealed that crystalline form of simvastatin existed in the formulation which was confirmed by X-ray powder diffraction. Dissolution studies indicated that there was a decrease in the drug release with an increase in the polymer viscosity. The tablets prepared with low-viscosity grade HPMC K4M exhibited short Buoyancy Lag Time and floated for a longer duration as compared with formulations containing high viscosity grade HPMC K100M. The ‘n’ value for dissolution studies for all the formulations was found to be in the range of 0.647 to 0.975 indicating non-Fickian or anomalous drug transport. Conclusion: The drug release rate and floating duration of tablets depended on the nature of the polymer and other added excipients. The release rate of the drug can be optimized by using different ratios of polymers and other excipients. The formulation F8 achieved the optimized batch and complied with all the properties of the tablets.

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