Viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solids for topical application to the oropharynx
Viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solids for topical application to the oropharynx
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DOI：
10.1023/a:1011906917084
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发表时间：
1998-07-01
影响因子：
3.7
通讯作者：
Brown, AF
中科院分区：
文献类型：
--
作者：
Jones, DS;Woolfson, D;Brown, AF
目的。本研究考察了用于口腔咽部局部应用的含洗必泰的生物粘附性半固体制剂的粘弹性。使用Carri-Med CSL2-100流变仪在20.0+/-0.1℃结合平行板几何形状(直径2厘米，样品厚度0.5 mm)进行振荡流变仪。样品承受恒定应变(6.5×10(-3)rad)，并在规定的频率范围(0.01-1.0 Hz)内测量确定的粘弹性参数，即储能模数(G‘)、损耗模数(G“)、损耗角正切(Tan 6)和动态粘度(Eta’)。结果：随着振荡频率的增加，所有制剂的G‘G”增大，而eTA’和tan 6均显著减小。G‘和G“随频率的增加幅度较小，说明配方总体上是非交联型弹性体系，随着HEC、PVP和PC浓度的增加，G’、G”、ETA‘显著增大，tan Delta减小，这可能与配方中各聚合物的物理状态有关。由于溶解组分(即HEC和PVP)的聚合链的缠结程度增加，以及PC的膨胀、交联链的伸长受到抑制，配方弹性增加(即tan Delta下降)。此外，在PVP的饱和溶解度超过和/或没有足够的“自由水”可用于PC的最大溶胀的配方中，配方弹性因PVP和/或PC的分散固体颗粒质量增加而增加。由于聚合物链缠结和聚合物状态对配方整体粘度的影响，配方Eta‘增加。在口咽部应用后，这些配方将表现为弹性系统。因此，这些制剂有望提供有利的临床特性，例如，延长药物释放时间，增加生物粘附性。然而，值得注意的是，临床评估的最终配方选择将涉及粘弹性特性和可接受的质地特性之间的折衷，例如产品应用的简便性。这项研究已经证明了振荡流变仪在临床评估中用于表征和选择候选局部生物黏附制剂的适用性。
Purpose. This study examined the viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solid formulations, designed for topical application to the oropharynx.Methods. Oscillatory rheometry was performed using a Carri-Med CSL2-100 rheometer at 20.0 +/- 0.1 degrees C in conjunction with parallel plate geometry (2 cm diameter, 0.5 mm sample thickness). Samples were subjected to a constant strain (6.5 x 10(-3) rad) and defined viscoelastic parameters, namely storage modulus (G'), loss modulus (G "), loss tangent (tan 6) and dynamic viscosity (eta'), measured over a defined frequency range (0.01-1.0 Hz).Results. As the oscillatory frequency was increased, G' G " of all formulations increased, whereas both eta' and tan 6 significantly decreased. The magnitude of increase of G' and G " as a function of frequency was relatively small, indicating that, in general, the formulations were non-cross-linked elastic systems. Increasing concentrations of HEC, PVP and PC significantly increased G', G ", eta' yet decreased tan delta, observations that may be attributed to the physical state of each polymer in the formulations. Formulation elasticity increased (i.e. tan delta decreased) as a result of increased entanglement of polymeric chains of dissolved components (i.e. HEC and PVP) and the restrained extension of swollen, cross-linked chains of PC. Additionally, in formulations where the saturation solubility of PVP was exceeded and/or insufficient "free-water" was available for maximal swelling of PC, formulation elasticity increased as a result of the increasing mass of dispersed solid particles of PVP and/or PC. Formulation eta' increased due to the attendent effects of polymer chain entanglement and polymer state on overall formulation viscosity.Conclusions. Following application to the oropharynx, the formulations will behave as elastic systems. Thus, these formulations would be expected to offer advantageous clinical properties, e.g., prolonged drug release, increased bioadhesion. However, it is noteworthy that the final choice of formulation for clinical evaluation will involve a compromise between viscoelastic characteristics and acceptable textural properties, e.g. ease of product application. This study has shown the applicability of oscillatory rheometry for both the characterisation and selection of candidate, topical bioadhesive formulations for clinical evaluation.