g-taste(G-TASTE顺序)怎么可以错过

Taste Masking – There’s More Beneath the Hood than Bit

 

Taste Masking – There’s More Beneath the Hood than Bitterness

It is widely recognized that many Active Pharmaceutical Ingredients (APIs) are bitter, some extremely so. But bitterness is not the only challenge in creating palatable, patient-accepted drug products.

人们普遍认为，许多活性药物成分(APIs)是苦的，有些是非常苦的但是，苦味并不是制造美味、患者接受的药品的唯一挑战What are some of the other aversive sensory attributes?。

还有哪些其他令人厌恶的感官属性?To answer this question, Senopsys compiled data from 101 API taste assessment studies and the results are summarized in the pie chart below (excludes over-the-counter drugs).

为了回答这个问题，Senopsys收集了101项API口味评估研究的数据，并将结果总结在下面的饼状图中(不包括非处方药)。

For almost three quarters of the APIs, mostly new chemical entities (NCEs), the primary taste masking challenge was bitterness. Of the other basic tastes, a few were sour (2%) or salty (combined into the “Other” category). None were found to be sweet.

对于近四分之三的原料药，主要是新化学实体(NCEs)，主要的味道掩盖挑战是苦味在其他基本口味中，有一些是酸的(2%)或咸的(合并到“其他”类别中)没有一种是甜的Obnoxious odors (malodors) represented the primary sensory challenge for approximately 10% of APIs. Some of the descriptors of these malodors include “phenolic” (like Band-Aids), “sulfidy” (overcooked cruciferous vegetables), “oxidized oil” (like old paint), and “solventy” (e.g., acetone).。

令人讨厌的气味(异味)代表了大约10%的原料药的主要感官挑战这些气味的一些描述词包括“酚类”(如创可贴)，“硫化物”(煮过头的十字花科蔬菜)，“氧化油脂”(如旧油漆)和“溶剂性”(如丙酮)The primary challenge for 8% of the APIs was a strong intensity trigeminal irritancy (e.g., burning).。

8%的原料药的主要挑战是强烈的三叉神经刺激(如灼烧)Finally, 7% of APIs were fundamentally tasteless, but their challenge was driven by the negative sensory attributes of the excipient system.。

最后，7%的原料药基本上是无味的，但他们的挑战是由辅料系统的负面感官属性驱动的Most APIs have multiple aversive attributes!大多数API都有多个令人反感的属性!。

There’s a general misconception that most APIs have a single aversive attribute but that’s not our experience. The pie chart belowshows the secondary aversive attributes. Unlike the bitter-weighted primary challenge, these secondary challenges are evenly divided between sour basic taste, aromatics (malodor) and trigeminal irritancy. While these are results from Senopsys studies and may not be representative of all APIs, its safe to say palatability issues go beyond bitterness!

有一种普遍的误解是，大多数API都有一个令人反感的属性，但我们的经验并非如此下面的饼状图显示了次级厌恶属性与苦味为主的主要挑战不同，这些次要挑战平均分为酸味、芳香(恶臭)和三叉神经刺激虽然这些是Senopsys研究的结果，可能不能代表所有API，但可以肯定地说，。

药物的适口性问题不仅仅是苦味!

Why is it important to identify the aversive sensory attributes?为什么识别厌恶的感官属性很重要?Just like the first step that my mechanic took in fixing a car was to determine which part is broken, diagnosing the challenge of the API is a formulator’s first step is fixing a “palatability” issue. Taste, smell, and irritation represent different perception pathways and importantly, the approach for dealing with each is fundamentally different.

就像我的机械师修理汽车的第一步是确定哪个部分坏了一样，诊断API的挑战是配方师的第一步，是解决“适口性”问题味觉、嗅觉和刺激代表不同的感知途径，重要的是，处理它们的方法根本不同As we discussed in an earlier 。

post, “Taste” refers to those sensations – sweet, sour salty and bitter – perceived through stimulation of the receptor cells located in the taste buds on the tongue and oral cavity. Taste issues are addressed via balancing their intensity with the application of other basic tastes to minimize the perception of each individually.

正如我们在之前的一篇文章中讨论过的，“味觉”指的是那些感觉——甜、酸、咸、苦——通过刺激舌头和口腔味蕾中的受体细胞来感知味觉问题是通过平衡它们的强度与其他基本味觉的应用来解决的，以尽量减少每种味觉的感知。

Negative aromas may be minimized through the judicious incorporation of commercial “flavors” which are mixtures of aroma chemicals that are perceived through the sense of smell (olfaction) – orange, strawberry, mint. These have no effect in reducing bitterness or the other so called basic tastes – sweet, sour and salty.。

通过明智地加入商业“香精”，可以将负面的气味降至最低商业“香精”是通过嗅觉(嗅觉)感知到的芳香化学物质的混合物——橙子、草莓、薄荷这些对减少苦味或其他所谓的基本味道——甜、酸和咸——没有作用Similarly, compounds such as capsicum (red pepper), piperine (black pepper) and many APIs produce a burning sensation when the Trigeminal nerve is activated (chemesthesis). The addition of tastants or odorants (flavors) has no effect on burning in the same way aspirin would not be administered to treat a bacterial infection.。

同样，辣椒(红辣椒)、胡椒碱(黑胡椒)等化合物和许多原料药在三叉神经被激活时产生灼烧感(化学感觉)添加调味剂或气味剂(香料)对灼烧没有影响，就像阿司匹林不能用于治疗细菌感染一样So how are the critical aversive sensory attributes measured to diagnose the problem?。

那么，如何测量关键的厌恶感官属性来诊断问题呢?Many approaches have been explored over the years to characterize and quantify the sensory attributes of APIs and drug products. These include non-human in-vivo models, in-vitro techniques and sensory analysis by trained subjects, as described in an earlier 

post. While many of the in-vivo and in-vitro techniques may provide an indication of a palatability issue, sensory analysis using trained subjects remains the definitive method for identifying and quantifying the attributes of APIs and drug products.

多年来已经探索了许多方法来表征和量化原料药和药品的感官属性这些包括非人类体内模型、体外技术和受过训练的受试者的感官分析，如之前的一篇文章所述虽然许多体内和体外技术可能提供适口性问题的指示，但使用受过训练的受试者进行感官分析仍然是识别和量化原料药和药品属性的确定方法。

Quantitative sensory analysis is an analytical technique used to identify and quantify the basic taste, aroma, irritation, and texture of drug actives and formulations. Senopsys uses the Flavor Profile quantitative sensory analysis method, an internationally recognized, open-source (i.e., non-proprietary) method of sensory analysis.。

定量感官分析是一种用于识别和量化药物活性成分和配方的基本滋味、香气、刺激性和质地的分析技术Senopsys使用风味轮廓定量感官分析方法，这是一种国际公认的开源(即非专有)感官分析方法To illustrate quantitative sensory analysis in practice, shown below are the Flavor Profile results for an NCE indicated for oncology. Clinical studies of the drug were truncated due to strong positive results in adults and a pediatric dosage form was urgently required. The analysis was conducted to identify and quantify the aversive sensory attributes of the API as necessary to inform the development of a palatable, age-appropriate formulation.。

为了说明定量感官分析在实践中的应用，下图显示了用于肿瘤学的NCE的风味分析结果该药物的临床研究由于在成人中有强烈的阳性结果而被截断，迫切需要儿科剂型该分析是为了识别和量化API的厌恶感官属性，以便为开发适龄配方提供必要的信息。

。

In Flavor Profile analysis, the panelists separate flavor into its components, measuring the individual attributes in the order they were perceived. Conceptually, the initial (Time = 0) sensory data is analogous to a chromatogram depicting a complex mixture separated into its individual chemical constituents.

在风味轮廓分析中，小组成员将风味分成其组成部分，按照感知到的顺序测量各个属性。从概念上讲，初始(时间= 0)的感官数据类似于色谱图，描绘了一个复杂的混合物，分为其单独的化学成分。

Palatable drug products are those in which the aversive sensory attributes are below the perception threshold

, which corresponds to a 1 on the Flavor Profile scale. Clearly the oncology API represents a multidimensional taste challenge, specifically sour and bitter basic tastes, mercaptan (skunky) aromatics, and burning and tannin mouthfeels.

可口的药品是那些令人厌恶的感官属性低于感知阈值的药品，这相当于风味特征量表上的1分显然，肿瘤学API代表了多维的味觉挑战，特别是酸和苦的基本味道，硫醇(臭)气味，灼烧和单宁的口感Many foods and beverages have strong intensity attributes that are perceived immediately upon mastication but quickly diminish in the aftertaste. In contrast, the aversive attributes of many APIs can linger in the aftertaste for 10, 20, 30 minutes or even hours. From a taste masking perspective, ameliorating the lingering effects of long-lived bitterness is far more challenging than short acting compounds such as caffeine. As shown below for the oncology API, skunky aromatics faded quickly in the aftertaste, as did sourness. However bitterness and mouthfeels lingered for at least 30 minutes.。

许多食物和饮料具有强烈的强度属性，咀嚼时立即感受到，但在回味时迅速减弱相比之下，许多原料药的令人厌恶的属性可以在回味中停留10分钟，20分钟，30分钟甚至几个小时从掩盖味道的角度来看，改善长期存在的苦味的影响远比咖啡因等短效化合物更具挑战性。

。如下图所示，对于肿瘤学API，难闻的芳香在回味中很快消失，酸味也是如此。然而，苦味、灼烧感和单宁口感持续了至少30分钟。

The oncology API represents a very difficult taste masking challenge less due to the intensity and more so the duration of multiple aversive taste, smell and trigeminal attributes. Based on empirical formulation experience, a technology that effectively “sequesters” the API from the receptors such as particle coating/encapsulation, complexation or adsorption will be required to develop a palatable pediatric formulation for this drug product.

肿瘤学API代表了一个非常困难的味道掩盖挑战，较少是由于强度，更多是由于多重厌恶味道，气味和三叉神经属性的持续时间根据处方经验，需要一种有效地将原料药与受体“隔离”的技术，如颗粒包衣/包封、络合或吸附，才能为该药物开发出可口的儿科配方。

Running Diagnostics is Key.运行诊断是关键Analytical sensory analysis using trained panelists ensures that the aversive attributes of the API (and excipients) are correctly identified and quantified. Conducting sensory analysis early in clinical development – ideally immediately following successful safety/pharmacokinetic studies – helps reduce technical risks associated with developing palatable, taste masked drug products.。

使用经过培训的小组成员进行分析感官分析，确保原料药(和辅料)的不良属性被正确识别和量化在临床开发的早期进行感官分析——最好是在成功的安全性/药代动力学研究之后立即进行——有助于减少与开发美味、掩盖味道的药物产品相关的技术风险。

Taste Masking Challenge? Senopsys Can Help!掩盖味道挑战?Senopsys可以帮你!Are you faced with the need to develop a palatable drug product to support clinical trials or commercial development?  Our scientists are expert in both taste assessment and taste masking.。

您是否需要开发一种可口的药物来支持临床试验或商业开发?我们的科学家是味觉评估和味觉掩饰方面的专家We use our experienced GCP-compliant taste panels and analytic tools to quantify the taste masking challenge and guide formulation development. And we apply a structured, sensory-directed development approach pioneered in the food industry to create palatable, taste-masked drug formulations for liquids, powders and solids.。

我们使用我们经验丰富的符合GCP的滋味评价小组和分析工具来量化滋味掩盖挑战并指导配方开发我们采用结构化的、感官导向的开发方法，开创了食品行业，为液体、粉末和固体创造美味的、掩盖味道的药物配方原文出处：https://www.senopsys.com/taste-masking-blog/taste-masking-theres-beneath-hood-bitterness/