Contribution to the rheological testing of pharmaceutical semisolids

Rheological behaviour of pharmaceutical semisolid preparations significantly affects manufacturing process, administration, stability, homogeneity of incorporated drug, accuracy of dosing, adhesion in the place of application, drug release, and resulting therapeutic effect of the product. We performed test of consistency by penetrometry, rotational, oscillation and creep tests, and squeeze and tack tests of model samples to introduce methods suitable for characterization and comparison of semisolids in practice. Penetrometry is a simple method allowing sorting the semisolids to low and high stress-resistant materials but deficient for rheological characterization of semisolids. Value of yield stress, generally considered to be appropriate feature of semisolids, is significantly influenced by the method of testing and the way of evaluation. The hysteresis loops of model semisolids revealed incomplete thixotropy, therefore, three-step thixotropy test was employed. Semisolids showed nonlinear response in the creep phase of tests and partial recovery of structure by storing energy in the recovery phase. Squeeze and tack tests seem to be convenient ways for comparison of semisolids. Our study can contribute to a better understanding of different flow behaviour of semisolids given by different physicochemical properties of excipients and can bring useful approaches to evaluation and comparison of semisolids in practice.     

Sensory regulation and mechanical effects of sustained high intensity stretching of the anterior compartment of the thigh

BackgroundBallet dancers, contortionists, gymnasts, or other sportspeople spend long hours performing stretches while training. Although most studies on stretching consider fascia lengthening to be difficult, athletes manage to lengthen their fascia.AimTo assess the relationship between lengthening fascial structures of the anterior compartment of the thigh and the self-reported sensation of discomfort and pain during a sustained and repeated high intensity stretch.MethodsOur analysis was based on the data of 7 high school male elite rugby players who completed 11 sessions of stretching (10-min quasi-static stretch of the rectus femoris and fascia lata, at the maximum intensity tolerated), performed twice per week. The measured outcomes included hip range of motion, the length of the structures of the anterior compartment, subjective pain and tension during the stretch, and the level of surface electromyography activity. Values were compared before and after completion of the 11 sessions.ResultsMyofascial length increased by 1 cm. The necessary force applied increased from 124 to 164 N. However, the maximal tolerated stretching intensity did not change significantly (from 205 to 206 N). The increase in length was principally contributed by the rate of fascial creep upon force application, and not by contractile tissue. Subjective levels of tension were related to the stretching force applied and pain was related to the lengthening.ConclusionSensations can be used to adjust the intensity and duration of stretching. Soft matter physics provides a new interpretation of fascia lengthening and strengthening during a high intensity stretch.     

Three-dimensional finite-element model of the human temporomandibular joint disc during prolonged clenching

In the temporomandibular joint (TMJ), overloading induced by prolonged clenching appears to be important in the cascade of events leading to disc displacement. In this study, the effect of disc displacement on joint stresses during prolonged clenching was studied. For this purpose, finite-element models of the TMJ, with and without disc displacement, were used. Muscle forces were used as a loading condition for stress analysis during a time-period of 10 min. The TMJ disc and connective tissue were characterized as a linear viscoelastic material. In the asymptomatic model, large stresses were found in the central and lateral part of the disc through clenching. In the retrodiscal tissue, stress relaxation occurred during the first 2 min of clenching. In the symptomatic model, large stresses were observed in the posterior part of the disc and in the retrodiscal tissue, and the stress level was kept constant through clenching. This indicates that during prolonged clenching the disc functions well in the asymptomatic joint, meanwhile the retrodiscal tissue in the symptomatic joint is subject to excessive stress. As this structure is less suitable for bearing large stresses, tissue damage may occur. In addition, storage of excessive strain energy might lead to breakage of the tissue.     

具有双特征时间参数的生物软组织黏弹性性质的理论研究

目的 探索描述生物软组织黏弹性特性的普遍行为或规律。方法 根据生物软组织的力学结构,构建由两个线性弹簧和两个黏壶的不同组合构成的四元件黏弹性结构模型;并通过弹性理论,结合不同黏弹性模型的几何构型推导其运动微分方程,利用其微分方程分析不同四元件模型的应力松弛和蠕变行为以及反映弹性和黏性相结合的应力松弛时间和蠕变推迟时间。结果 所有可能的四元件黏弹性模型都具有普遍的本构关系、应力松弛和蠕变函数形式。通过比较模型预测结果与主动脉瓣、韧带和脑动脉等生物软组织的实验数据发现,四元件黏弹性模型能够很好地描述生物软组织的力学行为。“快”和“慢”两个特征时间τ1和τ2对生物软组织的应力松弛具有显著的影响。“快”松弛时间τ1对应力达到稳定态所需时间有明显的影响,而“慢”松弛时间τ2对松弛率的影响不显著,但对应力松弛的稳定态有明显的影响。结论 生物软组织的时间依赖性行为可以通过两个特征时间尺度来表征,即“快”和“慢”时间;且具有两个特征时间的生物软组织的应力 应变关系、应力松弛和蠕变函数具有相同的数学形式,这与所选择的弹簧和黏壶的配置和排列无关,但为保证模型力学参数的合理性,针对不同的生物软组织应选取适合的模型。     

Effects of stress‐shielding on the dynamic viscoelasticity and ordering of the collagen fibers in rabbit Achilles tendon

We investigated the effects of stress‐shielding on both viscoelastic properties and microstructure of collagen fibers in the Achilles tendon by proton double‐quantum filtered (¹H‐DQF) NMR spectroscopy. The right hind‐limbs of 20 Japanese white rabbits were immobilized for 4 weeks in a cast with the ankle in plantarflexion. Dynamic viscoelasticity of the Achilles tendons was measured using a viscoelastic spectrometer. Proton DQF NMR signals were analyzed to determine the residual dipolar coupling of bound water molecules in the Achilles tendons. Both the dynamic storage modulus (E′) and dynamic loss modulus (E″) decreased significantly in the Achilles tendons of the stress‐shielding group. The results of the ¹H‐DQF NMR examination demonstrated significantly reduced residual dipolar coupling in the Achilles tendons of this same group. The disorientation of collagen fibers by stress‐shielding should contribute to degradation of the dynamic storage and loss moduli. The alterations of the collagen fiber orientation that contributed to the function of tendinous tissue can be evaluated by performing an analysis of ¹H DQF NMR spectroscopy. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1708–1712, 2013     

A cross-sectional study to compare intraocular pressure measurement by sequential use of Goldman applanation tonometry,dynamic contour tonometry,ocular response analyzer,and Corvis ST

Objective:

To study the correlation and effect of sequential measurement of intraocular pressure (IOP) with Goldmann applanation tonometer (GAT), ocular response analyzer (ORA), dynamic contour tonometer (DCT), and Corvis ST.

Setting and Design:

Observational cross-sectional series from the comprehensive clinic of a tertiary eye care center seen during December 2012.

Methods:

One hundred and twenty-five study eyes of 125 patients with normal IOP and biomechanical properties underwent IOP measurement on GAT, DCT, ORA, and Corvis ST; in four different sequences. Patients with high refractive errors, recent surgeries, glaucoma, and corneal disorders were excluded so as to rule out patients with evident altered corneal biomechanics.

Statistical Analysis:

Linear regression and Bland–Altman using MedCalc software.

Results:

Multivariate analysis of variance with repeated measures showed no influence of sequence of device use on IOP (P = 0.85). Linear regression r² between GAT and Corvis ST, Corvis ST and Goldmann-correlated IOP (IOPg), and DCT and Corvis ST were 0.37 (P = 0.675), 0.63 (P = 0.607), and 0.19 (P = 0.708), respectively. The Bland–Altman agreement of Corvis ST with GAT, corneal compensated IOP, and IOPg was 2 mmHg (−5.0 to + 10.3), −0.5 mmHg (−8.1 to 7.1), and 0.5 mmHg (−6.2 to 7.1), respectively. Intraclass correlation coefficient for repeatability ranged from 0.81 to 0.96.

Conclusions:

Correlation between Corvis ST and ORA was found to be good and not so with GAT. However, agreement between the devices was statistically insignificant, and no influence of sequence was observed.     

Strain-rate-dependent non-linear tensile properties of the superficial zone of articular cartilage

Aim of the study: The tensile properties of articular cartilage play an important role in the compressive behavior and integrity of the tissue. The stress-strain relationship of cartilage in compression was observed previously to depend on the strain-rate. This strain-rate dependence has been thought to originate mainly from fluid pressurization. However, it was not clear to what extent the tensile properties of cartilage contribute to the strain-rate dependence in compressive behavior of cartilage. The aim of the present study was to quantify the strain-rate dependent stress-strain relationship and hysteresis of articular cartilage in tension.

Methods: Uniaxial tensile tests were performed to examine the strain-rate dependent non-linear tensile properties of the superficial zone of bovine knee cartilage. Tensile specimens were oriented in the fiber direction indicated by the India ink method. Seven strain-rates were used in the measurement ranging from 0.1 to 80%/s, which corresponded to nearly static to impact joint loadings.

Results: The experimental data showed substantial strain-rate and strain-magnitude dependent load response: for a given strain-magnitude, the tensile stress could vary by a factor of 1.95 while the modulus by a factor of 1.58 with strain-rate; for a given strain-rate, the modulus at 15% strain could be over four times the initial modulus at no strain. The energy loss in cartilage tension upon unloading exhibited a complex variation with the strain-rate.

Conclusion: The strain-rate dependence of cartilage in tension observed from the present study is relatively weaker than that in compression observed previously, but is considerable to contribute to the strain-rate dependent load response in compression.     

A New Viscoelasticity Dynamic Fitting Method Applied for Polymeric and Polymer-Based Composite Materials

The accurate analysis of the behaviour of a polymeric composite structure, including the determination of its deformation over time and also the evaluation of its dynamic behaviour under service conditions, demands the characterisation of the viscoelastic properties of the constituent materials. Linear viscoelastic materials should be experimentally characterised under (i) constant static load and/or (ii) harmonic load. In the first load case, the viscoelastic behaviour is characterised through the creep compliance or the relaxation modulus. In the second load case, the viscoelastic behaviour is characterised by the complex modulus, E*, and the loss factor, η. In the present paper, a powerful and simple implementing technique is proposed for the processing and analysis of dynamic mechanical data. The idea is to obtain the dynamic moduli expressions from the Exponential-Power Law Method (EPL) of the creep compliance and the relaxation modulus functions, by applying the Carson and Laplace transform functions and their relationship to the Fourier transform, and the Theorem of Moivre. Reciprocally, once the complex moduli have been obtained from a dynamic test, it becomes advantageous to use mathematical interconversion techniques to obtain the time-domain function of the relaxation modulus, E(t), and the creep compliance, D(t). This paper demonstrates the advantages of the EPL method, namely its simplicity and straightforwardness in performing the desirable interconversion between quasi-static and dynamic behaviour of polymeric and polymer-composite materials. The EPL approximate interconversion scheme to convert the measured creep compliance to relaxation modulus is derived to obtain the complex moduli. Finally, the EPL Method is successfully assessed using experimental data from the literature.     

Cerebral multifrequency MR elastography by remote excitation of intracranial shear waves

The aim of this study was to introduce remote wave excitation for high‐resolution cerebral multifrequency MR elastography (mMRE). mMRE of 25–45‐Hz drive frequencies by head rocker stimulation was compared with mMRE by remote wave excitation based on a thorax mat in 12 healthy volunteers. Maps of the magnitude |G*| and phase φ of the complex shear modulus were reconstructed using multifrequency dual elasto‐visco (MDEV) inversion. After the scan, the subjects and three operators assessed the comfort and convenience of cerebral mMRE using two methods of stimulating the brain. Images were acquired in a coronal view in order to identify anatomical regions along the spinothalamic pathway. In mMRE by remote actuation, all subjects and operators appreciated an increased comfort and simplified procedural set‐up. The resulting strain amplitudes in the brain were sufficiently large to analyze using MDEV inversion, and yielded high‐resolution viscoelasticity maps which revealed specific anatomical details of brain mechanical properties: |G*| was lowest in the pons (0.97 ± 0.08 kPa) and decreased within the corticospinal tract in the caudal–cranial direction from the crus cerebri (1.64 ± 0.26 kPa) to the capsula interna (1.29 ± 0.14 kPa). By avoiding onerous mechanical stimulation of the head, remote excitation of intracranial shear waves can be used to measure viscoelastic parameters of the brain with high spatial resolution. Therewith, the new mMRE method is suitable for neuroradiological examinations in the clinic. Copyright © 2015 John Wiley & Sons, Ltd.     

Effect of Force of Microneedle Insertion on the Permeability of Insulin in Skin

Many experiments conducted in the literature have investigated the effect of microneedles (MNs) on insulin permeation across skin. There are also a number of articles that deal with the effect of MN insertion force in skin. However, there is little known on quantifying the relationship between the effect of MN insertion force and the amount of insulin permeated for given MNs. This issue is addressed in this article. MNs of 1100 µm and 1400 µm are used to conduct in vitro permeability experiments on porcine skin, using insulin. Histological images of MN treated skin are obtained from a microtome and the viscoelastic properties of the skin sample are measured using a rheometer. An in-house insertion force device is utilized that can reproducibly apply a specified force on MNs for a set period of time using compressed air. It is deduced that when porcine skin was pretreated with an applied force of 60.5 N and 69.1 N, the resultant amount of insulin permeated was approximately 3 µg and 25 µg over a 4-hour period for the MNs used. The amount of MN force applied to porcine skin was shown to be related to the amount of insulin permeated. An increase in insertion force increase the amount of insulin permeated. It was also demonstrated that using insufficient force may have reduced or prevented the amount of insulin passing through the skin, regardless of the geometry of the MNs.