The Role of Essential Oils in Homemade Cosmetics: A Study of 140 Recipes.

Two recent trends that have developed simultaneously are a mistrust of health products by some of the population and the growing popularity of essential oils. The objective of this study was to analyze recipes with essential oils found on the internet and to assess their level of photoprotective efficacy. Therefore, we conducted a study of 140 recipes for personal care and hygiene products that incorporate one or more essential oils. This analysis revealed that numerous essential oils are called for in these recipes, derived from plants belonging to a wide diversity of botanical families. There was a significant difference (p=0.0026) in the number of essential oils listed in the recipes for facial care and body care recipes. There was also a statistically significant difference (p=2.54E-5) in the amount of essential oil to be added, expressed in drops, according to the type of product being made. A common characteristic of most of the recipes was the absence of any antimicrobial agents or antioxidants, which poses serious issues of preservation for the finished products. Recipes with essential oils pose many issues. The first issue lies in the quantities of the different raw materials to be incorporated; it influences the final essential oil concentration. The second issue concerns the adverse effects (photosensitization, for example) and contraindications (pregnant women, nursing women) of certain essential oils. Finally, it is not possible to carry out physicochemical testing raw materials and finish preparation.

Study of the composition of 140 shampoos: similarities and differences depending on the sales channel used.

Shampoo is a hair care product designed to clean the skin and hair of the scalp. Among the ingredients that go into the making of a shampoo are detergents, conditioners, thickeners, sequestering agents, pH adjusters, preservatives, and active ingredients such as anti-dandruff agents. The purpose of this study was to identify the composition of 140 shampoos available in pharmacies, in stores of a mass-market chain, or from mail-order retailers. Forty-one shampoos were advertised as "gentle", 12 as specially formulated for infants, 35 as anti-dandruff, and 52 without any particular claim. We analysed the cleansing base, preservatives, and anti-dandruff agents when relevant and identified the allergens regardless of whether or not they are listed under Regulation (EC) No. 1223/2009 as one of the 26 regulated substances. We discovered that unlike shampoos sold in stores of a mass-market chain and those available from mail-order retailers, those sold in pharmacies expose users to some of the 26 substances listed under Regulation (EC) No. 1223/2009. We also determined that baby shampoos sold in pharmacies are allergen-free. Regarding anti-dandruff formulations, the largest variety of active ingredients was found in shampoos sold in pharmacies. Overall, the most common active ingredients were olamines, zinc pyrithione, azoles, selenium disulphide, and plant extracts. Shampoos sold in pharmacies appear to contain fewer allergens listed under Regulation (EC) No. 1223/2009 compared to those sold elsewhere.

Lamination of biconvex tablets: Numerical and experimental study.

Capping and lamination are common industrial problems during the manufacturing of pharmaceutical tablets. Even if they are commonly treated together, these phenomena correspond to different failure patterns of the tablet and, as a consequence, to different mechanisms of cracking. In this work, a specific case of lamination of biconvex tablets was studied. It corresponds to a breakage into two parts of the tablets along a failure plan normal to the compression direction and located approximately at the center of the tablet band. Simulation with finite element method made it possible to propose that this kind of failure is promoted by tensile stresses localized at the center of the tablet that are induced by the residual die wall pressure and the tablet shape. Moreover, these stresses are favored by a small band thickness. Experimental results confirmed these hypotheses and also showed that this kind of lamination was favored by a high compaction pressure. As the crack is formed at the center of the tablet, it may not propagate until the tablet band. Failure may thus remain undetected by external visual examination. X-ray tomography made it possible to observe central cracks inside the tablet without tablet breakage. The possibility to have such cracks inside the tablet must be considered during tablet development as, even if not detected just after compression, they could lead to tablet failure during post compaction events.

Effect of the Curvature of the Punches on the Shape of the Interface and the Delamination Tendency of Bilayer Tablets.

Bilayer tablets are of special interest in the pharmaceutical industry. The main problem during their manufacturing is the occurrence of delamination during or after the ejection from the die. This work studies the influence of using punches with a curvature on the interfacial strength and thus on the delamination tendency of bilayer tablets. Bilayer tablets were produced with a compaction simulator using different flat and concave punches with different radii of curvature. The main compaction pressure was kept constant but the tamping force was varied. Two bilayer model systems were studied. The interfacial strength was determined using a previously described indentation test. The factors studied were analyzed for statistical significance with respect to the responses. The curvature of the interface was found to be higher when the curvature of the punch and the tamping force increased. Breaking tests then demonstrated that, for bilayer tablets obtained using the same compression parameters, the interfacial strength was lower when the curvature of the interface increased. As a consequence, when producing bilayer tablets with concave punches, it is important to choose properly the tableting parameters in order to have an interface between the layers as flat as possible to avoid delamination issues.

Comparison of breaking tests for the characterization of the interfacial strength of bilayer tablets.

The bilayer tableting technology is gaining more acceptance in the drug industry, due to its ability to improve the drug delivery strategies. It is currently assessed by the European Pharmacopoeia, that the mechanical strength of tablets can be evaluated using a diametral breaking tester. This device applies a force diametrically, and records the tablet breaking point. This approach has been used to measure the structural integrity of single layer tablets as well as bilayer (and multi-layer) tablets. The latter ones, however, have a much complex structure. Therefore, testing a bilayer tablet with the currently used breaking test methodology might not be appropriate. The aim of this work was to compare results from several tests that have been proposed to quantify the interfacial strength of bilayer tablets. The obtained results would provide an indication on which tests are appropriate to evaluate the robustness of a bilayer tablet. Bilayer tablets were fabricated using a model formulation: Microcrystalline Cellulose (MCC) for the first layer, and spray dried lactose (SDLac) as second layer. Each set of tablets were tested using the following tests: Diametral Test, Shear Test and Indentation Test. The tablets were examined before and after the breaking test using Scanning Electron Microscopy (SEM). When a bilayer tablet was subjected to shearing or indentation, it showed signs of clear delamination. Differently, using the diametral test system, the tablets showed no clear difference, before and after the testing. However, when examining each layer via SEM, it was clear that a fracture occurred in the layer made of SDLac. Thus, the diametral test is a measure of the strength of one of the two layers and therefore it is not suited to test the mechanical strength of bilayer tablets.

Evolution of the Die-Wall Pressure during the Compression of Biconvex Tablets: Experimental Results and Comparison with FEM Simulation.

Capping is a classical manufacturing problem for tablets, which is known to affect more biconvex tablets than flat-faced ones. One reason could be the development of a higher residual die-wall pressure during unloading. Unfortunately, contradictory results were published on the subject. In this work, the evolution of the die-wall pressure during the compaction of biconvex tablets was studied experimentally and using finite element method (FEM) modeling. It was compared with the case of flat-faced tablets. Experimental and numerical results showed that during the compression of biconvex tablet, a lower maximum die-wall pressure and a higher residual die-wall pressure were obtained compared with the case of flat-faced tablet. Moreover, both approaches showed, for biconvex tablets, a temporary increase of the die-wall pressure at the end of the unloading phase. FEM demonstrated that this phenomenon was due to a gradual loss of contact between the punch and the tablet from the side to the center. This complex unloading behavior causes the temporary increase of the die-wall pressure and the development of a shear stress between the convex part and the land of the tablet. This could explain the capping tendency of biconvex tablets.

Investigating the effect of tablet thickness and punch curvature on density distribution using finite elements method.

Finite elements method was used to study the influence of tablet thickness and punch curvature on the density distribution inside convex faced (CF) tablets. The modeling of the process was conducted on 2 pharmaceutical excipients (anhydrous calcium phosphate and microcrystalline cellulose) by using Drucker-Prager Cap model in Abaqus(®) software. The parameters of the model were obtained from experimental tests. Several punch shapes based on industrial standards were used. A flat-faced (FF) punch and 3 convex faced (CF) punches (8R11, 8R8 and 8R6) with a diameter of 8mm were chosen. Different tablet thicknesses were studied at a constant compression force. The simulation of the compaction of CF tablets with increasing thicknesses showed an important change on the density distribution inside the tablet. For smaller thicknesses, low density zones are located toward the center. The density is not uniform inside CF tablets and the center of the 2 faces appears with low density whereas the distribution inside FF tablets is almost independent of the tablet thickness. These results showed that FF and CF tablets, even obtained at the same compression force, do not have the same density at the center of the compact. As a consequence differences in tensile strength, as measured by diametral compression, are expected. This was confirmed by experimental tests.

Development of a new test for the easy characterization of the adhesion at the interface of bilayer tablets: proof-of-concept study by experimental design.

Although, adhesion at the interface of bilayer tablets is critical for their design it is difficult to characterize this adhesion between layers. In view of this, a new test with an easy implementation was proposed for the characterization of the interface of bilayer tablets. This work is presented as a proof-of-concept study to investigate the reliability of this new test with regard to the effects of some critical process parameters (e.g., compaction pressure applied on each layer) and material attributes (e.g., elasticity of the layered materials) on the interfacial adhesion of bilayer tablets. This was investigated using a design of experiment approach and the results obtained were in good accordance with those obtained with other tests and thus, confirms the potential of such a method for the measurement of the interfacial adhesion of bilayer tablets.

Comparison of different failure tests for pharmaceutical tablets: applicability of the Drucker-Prager failure criterion.

Several tests can be used to study the strength of pharmaceutical tablets. Equations exist in the literature to transform the failure force measured into a failure stress which can be considered as a characteristic of the strength of the material. For each failure test, the stress state at failure is different, and as a consequence, the failure stresses obtained are also different. It would thus be interesting to find a failure criterion to unify the different results. In this study four different tests were performed on pharmaceutical compacts of various densities: diametral compression, three-point flexure, biaxial flexure and uniaxial compressive tests. The Drucker-Prager criterion was tested as a possible fracture envelope. The results showed that this criterion is well suited to explain the failures obtained by diametral compression, three-point flexure and biaxial flexure. Nevertheless, for the uniaxial compressive test, the use of this criterion led to a significative underestimation of the experimental value of the failure stress. As a consequence, the Drucker-Prager criterion must be used with caution and is not able to explain all the failures that can occur in a pharmaceutical compact.

Study of the validity of the three-point bending test for pharmaceutical round tablets using finite element method modeling.

Mechanical strength is an important quality attribute of the tablets produced in the pharmaceutical industry. The three-point bending test is one of the methods described by the United States (US) pharmacopeia to test this property. In this work, finite element method modeling was perform to study the stress distribution in a round, flat tablet submitted to this test and to verify whether the equation given by US pharmacopeia to calculate the tensile strength could be used without restrictions. For this test, the center of the lower face of the tablet was submitted to the highest tensile stress and, at this point, the stress state was nearly uniaxial. This test is thus well suited to measure the tensile strength of pharmaceutical tablets. Moreover, simulations were performed with a large range of geometrical dimensions using the dimensionless parameters D/L and h/D (where D is the tablet diameter, h is the tablet thickness, and L is the distance between the supports). In order to obtain the value of the tensile strength with a good precision when using the equation given by the US pharmacopeia, the measurements should only be performed in a restricted area of the domain defined by D/L and h/D.

Role of the elasticity of pharmaceutical materials on the interfacial mechanical strength of bilayer tablets.

The effect of the elasticity of various pharmaceutical materials on the interfacial adhesion in bilayer tablets was investigated. The elastic properties of five pharmaceutical products were characterized by their total elastic recovery. To test the interfacial strength of the bilayer tablets a new flexural test was proposed. Thanks to the test configuration, the experimental breaking force is directly correlated with the interfacial layer strength. Depending on the materials, the fracture occurred over the interface or in one of the two layers. In most cases, the highest breaking forces were obtained when the materials had close elastic recovery. On the contrary, for materials with different elastic recovery, the breaking forces were reduced. The observed changes in the interfacial mechanical strength were statistically analyzed. Such an approach has an importance in the growing interest in the Quality by Design (QbD) concept in pharmaceutical industry.

On the links between elastic constants and effective elastic behavior of pharmaceutical compacts: importance of poisson's ratio and use of bulk modulus.

The elastic properties of pharmaceutical powders and compacts are of great interest to understand the complex phenomena that occur during and after the tableting process. The elastic recovery after compression is known to be linked with adverse phenomena such as capping or delamination of tablets. Classically, the elastic behavior is modeled using linear elasticity and is characterized using only Young's modulus (E), often by using a value extrapolated at zero porosity. In this work, four pharmaceutical products were studied. The elastic behavior of compacts obtained using a large range of applied pressure was characterized. First, it was found more suitable to use apparent elastic moduli than extrapolations at zero porosity. Then, the results indicate that there was not always a good correlation between the values of Young's modulus and the actual elastic recovery of the compacts. Poisson's ratio (v), which differs from one product to another and is porosity-dependent, must be taken into account. Finally, the bulk modulus (K), which combines E and v, was shown to be well correlated with the elastic recovery of the compacts and can be considered as a relevant parameter to characterize the elastic behavior of pharmaceutical compacts.

FEM simulation of the die compaction of pharmaceutical products: influence of visco-elastic phenomena and comparison with experiments.

This work studies the influence of visco-elastic behavior in the finite element method (FEM) modeling of die compaction of pharmaceutical products and how such a visco-elastic behavior may improve the agreement between experimental and simulated compression curves. The modeling of the process was conducted on a pharmaceutical excipient, microcrystalline cellulose (MCC), by using Drucker-Prager cap model coupled with creep behavior in Abaqus(®) software. The experimental data were obtained on a compaction simulator (STYLCAM 200R). The elastic deformation of the press was determined by performing experimental tests on a calibration disk and was introduced in the simulation. Numerical optimization was performed to characterize creep parameters. The use of creep behavior in the simulations clearly improved the agreement between the numerical and experimental compression curves (stresses, thickness), mainly during the unloading part of the compaction cycle. For the first time, it was possible to reproduce numerically the fact that the minimum tablet thickness is not obtained at the maximum compression stress. This study proves that creep behavior must be taken into account when modeling the compaction of pharmaceutical products using FEM methods.

Measurements of elastic moduli of pharmaceutical compacts: a new methodology using double compaction on a compaction simulator.

The elastic properties of pharmaceutical powders play an important role during the compaction process. The elastic behavior can be represented by Young's modulus (E) and Poisson's ratio (v). However, during the compaction, the density of the powder bed changes and the moduli must be determined as a function of the porosity. This study proposes a new methodology to determine E and v as a function of the porosity using double compaction in an instrumented compaction simulator. Precompression is used to form the compact, and the elastic properties are measured during the beginning of the main compaction. By measuring the axial and radial pressure and the powder bed thickness, E and v can be determined as a function of the porosity. Two excipients were studied, microcrystalline cellulose (MCC) and anhydrous calcium phosphate (aCP). The values of E measured are comparable to those obtained using the classical three-point bending test. Poisson's ratio was found to be close to 0.24 for aCP with only small variations with the porosity, and to increase with a decreasing porosity for MCC (0.23-0.38). The classical approximation of a value of 0.3 for ν of pharmaceutical powders should therefore be taken with caution.