The Effect of Process Parameters on the Microstructure, Stability, and Sensorial Properties of an Emulsion Cream Formulation.

A classical emulsion formulation based on petrolatum and mineral oil as the internal phase with emulsifier wax as a typical topical emulsion cream was investigated for the effect of process parameters on drug product quality and performance attributes. The Initial Design of Experiment (DoE) suggested that an oil phase above 15%, coupled with less than 10% emulsifying wax, resulted in less stable emulsions. Different processing parameters such as homogenization speed, duration, cooling rate, and final temperature showed minimal influence on properties and failed to improve stability. The final DoE suggested that the optimal emulsion stability was achieved by introducing a holding period midway through the cooling stage after solvent addition. Within the studied holding temperature range (25-35 °C), a higher holding temperature correlated with increased emulsion stability. However, the application of shear during the holding period, using a paddle mixer, adversely affected stability by disrupting the emulsion microstructure. IVRT studies revealed that the release of lidocaine was higher in the most stable emulsion produced at a holding temperature of 35 °C compared to the least stable emulsion produced at a holding temperature of 25 °C. This suggests that a holding temperature of 35 °C improves both the stability and active release performance. It appears that a slightly higher holding temperature, 35 °C, allows a more flexible and stable emulsifying agent film around the droplets facilitating stabilization of the emulsion. This study offers valuable insights into the relationship between process parameters at various stages of manufacture, microstructure, and various quality attributes of emulsion cream systems. The knowledge gained will facilitate improved design and optimization of robust manufacturing processes, ensuring the production of the formulations with the desired critical quality attributes.

Influence of Manufacturing Process on the Microstructure, Stability, and Sensorial Properties of a Topical Ointment Formulation.

The manufacturing process for ointments typically involves a series of heating, cooling, and mixing steps. Precise control of the level of mixing through homogenization and the cooling rate, as well as temperature at different stages, is important in delivering ointments with the desired quality attributes, stability, and performance. In this work, we investigated the influence of typical plant processing conditions on the microstructure, stability, and sensorial properties of a model ointment system through a Design of Experiments (DoE) approach. Homogenization speed at the cooling stage after the addition of the solvent (propylene glycol, PG) was found to be the critical processing parameter that affects stability and the rheological and sensorial properties of the ointment. A lower PG addition temperature was also found to be beneficial. The stabilization of the ointment at a lower PG addition temperature was hypothesized to be due to more effective encapsulation by crystallizing mono- and diglycerides at the lower temperature. The in vitro release profiles were found to be not influenced by the processing parameters, suggesting that for the ointment platform studied, processing affects the microstructure, but the effects do not translate into the release profile, a key performance indicator. Our systematic study represents a Quality-by-Design (QbD) approach to the design of a robust manufacturing process for delivering stable ointments with the desired performance attributes and properties.

Influence of wall slip, thixotropy and lubrication regime on the instrumental sensory evaluation of topical formulations.

OBJECTIVE: Drawing parallels from rheotribology can be used to develop a robust instrumental protocol for non-subjective characterization, product development and design of topical dosage forms with desired sensory attributes. However, instrumental characterization of cosmetic products can be influenced by the measurement protocol, thixotropy, flow anomalies like shear banding or wall slip and nature of the film formed on the skin surface. In this study, we evaluated the influence of above parameters on the instrumental sensory evaluation of 12 topical formulations of different galenic forms. METHODS: Oscillatory strain sweep measurements (SAOS and LAOS) were performed to investigate the influence of frequency and wall slip on the material parameters. The textural attributes at different consumer touchpoints were evaluated by accounting time-dependent simulation of viscoelastic flow. Further, the influence of film thickness and sample drying on the tactile properties of the topical formulations were studied on a non-biological skin model using a sliding probe tribometer. RESULTS: The study shows that the flow properties of the semi-solid formulations depend on the timescale of the problem. A few formulations exhibited wall slip to varying degrees in the linear viscoelastic regime where the behaviour was found not to be characteristic of a particular topical dosage form. The material functions obtained from the Lissajous plots suggest that the non-linear flow behaviour of different galenic forms is least influenced by the boundary conditions imposed by the measurement geometry. The results were statistically analysed using principal component analysis where the attributes used for discriminating skin creams during pick up and rub out are found to be closely associated with non-linear rheology. The friction coefficient exhibited speed dependence where it formed different parametric group with rheological data depending on the lubrication regime. CONCLUSION: The study highlights that correlations are possible amongst rheological, tribological and instrumental textural analysis data, which can act an impetus for the development of models to predict attributes that drive perception at different consumer touchpoints. However, the choice of instrumental settings, anomalies associated with rheological measurements and friction dependence on a number of parameters can influence the model prediction.

OBJECTIF: il est possible d'établir des parallèles à partir de la rhéotribologie pour développer un protocole instrumental robuste pour la caractérisation non subjective, le développement de produits et la conception de formes posologiques topiques avec les attributs sensoriels souhaités. Cependant, la caractérisation instrumentale des produits cosmétiques peut être influencée par le protocole de mesure, la thixotropie, les anomalies de flux comme la bande de cisaillement ou le glissement de fluides et la nature du film formé à la surface de la peau. Dans cette étude, nous avons évalué l'influence des paramètres ci-dessus sur l'évaluation sensorielle instrumentale de 12 formulations topiques de différentes formes galéniques. MÉTHODES: des mesures de balayage de la tension oscillatoire (SAOS et LAOS) ont été effectuées pour étudier l'influence de la fréquence et du glissement de fluides sur les paramètres des matériaux. Les attributs texturaux à différents points de contact avec les consommateurs ont été évalués en tenant compte de la simulation dépendante du temps du flux viscoélastique. En outre, l'influence de l'épaisseur du film et du séchage de l'échantillon sur les propriétés tactiles des formulations topiques a été étudiée sur un modèle cutané non biologique à l'aide d'un tribomètre à sonde coulissante. RÉSULTATS: l'étude montre que les propriétés de flux des formulations semi-solides dépendent de l'échelle de temps du problème. Quelques formulations ont montré un glissement de fluides à des degrés variables dans le régime viscoélastique linéaire où le comportement ne s'est pas avéré être caractéristique d'une forme posologique topique particulière. Les fonctions matérielles obtenues à partir des tracés de Lissajous suggèrent que le comportement de flux non linéaire des différentes formes galéniques est le moins influencé par les conditions limites imposées par la géométrie de la mesure. Les résultats ont été analysés statistiquement à l'aide d'une analyse en composante principale dans laquelle les attributs utilisés pour distinguer les crèmes cutanées lors du prélèvement et de la friction se sont avérés être étroitement associés à la rhéologie non linéaire. Le coefficient de frottement présentait une dépendance à la vitesse, où il formait un groupe paramétrique différent avec des données rhéologiques selon le régime de lubrification. CONCLUSION: l'étude souligne que des corrélations sont possibles entre les données d'analyses rhéologiques, tribologiques et instrumentales de la texture, pouvant donner une impulsion au développement de modèles permettant de prédire les attributs qui stimulent la perception à différents points de contact avec les consommateurs. Cependant, le choix des paramètres instrumentaux, les anomalies associées aux mesures rhéologiques et la dépendance à la friction sur un certain nombre de paramètres peuvent influencer la prédiction du modèle.