Moisturizing emulsion systems based on the novel long-chain alkyl polyglucoside emulsifier

Mesomorphic behavior of the novel long-chain alkyl polyglucoside emulsifier comprising arachidyl alcohol (C₂₀), behenyl alcohol (C₂₂), and arachidyl glucoside was investigated in order to determine the prevalent stabilization mechanism and moisturizing capacity of emulsion systems based on it. For this to be accomplished thermoanalytical methods (differential scanning calorimetry and thermogravimetric analysis) coupled with microscopy, rheological, X-ray diffraction methods and a short-term in vivo study of skin hydration level were performed. Obtained results have proved that C₂₀/C₂₂ alkyl polyglucoside mixed emulsifier is able to provide the synergism between the two main types of lamellar phases, the liquid-crystalline (Lα), and the gel crystalline (Lβ) one, building the emulsion systems of different stability and performance. Formation of lamellar structures influenced for more than one half of water within the system to be entrapped. Conducted investigation of hydration potential in real-time conditions provided valuable information on the investigated emulsion vehicles’ moisturizing potential as well as their contribution to the skin barrier improvement. Therefore, it could be expected that emulsions based on this alkyl polyglucoside emulsifier could influence the delivery of active ingredients of both the lipophilic and hydrophilic type. The employment of thermoanalytical methods in our work suggests the possibility for thermal methods to be used more frequently in the characterization of both the novel raw materials and the belonging emulsion systems.     

Compatibility study between indomethacin and excipients in their physical mixtures

Thermal analysis is a routine method for analysis of drugs and substances of pharmaceutical interest. Thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) are thermoanalytical methods which offer important information about the physical and chemical properties of drugs (purity, stability, phase transition, polymorphism, compatibility, kinetic analysis, etc.). This work exemplifies a general method of studying the drug-excipient interactions with the aim of predicting rapidly and inexpensively the long thermal stability of their mixtures. The TG/DTG and DSC were used as screening techniques for assessing the compatibility between indomethacin (IND) and its physical associations as binary mixtures with some common excipients. Based on their frequent use in preformulations eleven different excipients: corn starch, microcrystalline cellulose (PH 101; PH 102), colloidal silicon dioxide, lactose (monohydrate and anhydre), polyvinilpyrrolidone K30, magnesium stearate, talc, stearic acid, and manitol were blended with IND. The samples were prepared by mixing the analyte and excipients in a proportion of 1:1 (w:w). In order to investigate the possible interactions between the components, the thermal curves of IND and each selected excipient were compared with those of their 1:1 (w/w) physical mixtures. FT-IR spectroscopy and X-ray powder diffraction were used as complementary techniques to adequately implement and assist in interpretation of thermal results. On the basis of thermal results, confirmed by FT-IR and X-ray analyses, a possible interaction was found between IND with polyvinylpyrrolidone K30, magnesium stearate, and stearic acid.     

Compatibility of sildenafil citrate and pharmaceutical excipients by thermal analysis and LC–UV

The evaluation of sildenafil citrate (SC), the best-selling drug for treatment of impotence, for compatibility with various excipients was investigated using thermal and isothermal stress testing. Differential scanning calorimetry (DSC), hot-stage microscopy (HSM) and liquid chromatography (LC) with ultraviolet detection were successfully employed to investigate the compatibility between SC and various excipients commonly used in solid form in the pharmaceutical industry. The studies were performed using 1:1 (m/m) drug/excipient physical mixtures and samples were stored under accelerated stability conditions (40 °C at 75% relative humidity). All excipients tested (such as colloidal silicon dioxide, croscarmellose sodium, lactose, mannitol and sucrose) showed potential incompatibilities by DSC and LC analysis after accelerated stability testing. However, some incompatibilities were not detected by the DSC method and were observed only when LC analysis was performed. HSM was able to differentiate active pharmaceutical ingredient degradation from solubilisation, supporting the interpretation of DSC in excipients where thermal events either overlapped or disappeared. The combination of both the analytical techniques (DSC and LC) and use of a stability chamber is extremely helpful in detecting incompatibilities and providing more robust and accurate approaches for pre-formulation studies.     

Attainment of Emulsions with Liquid Crystal from Marigold Oil Using the Required HLB Method

Development of new formulations for topical use and cosmetic and pharmaceutical delivery agents has increased the complexity of emulsified systems. Liquid crystals, known since the nineteenth century are the third phase of an emulsion, being responsible for increasing its stability and the solubility of substances poorly soluble in water, or the oily phase, modulating the release of drugs imprisoned in its structure and promoting hydration of the skin surface. In the present work we developed oil/water emulsions, making use of Marigold oil (Calendula officinalis L) and ethoxylated fat alcohols as surfactant. The required HLB value for marigold oil was determined to be 6.0. The surfactants were associated in lipophilic/hydrophilic pairs. The lipophilic surfactants were Ceteth‐2 and Steareth‐2 and the hydrophilic surfactants were Steareth‐20, Ceteareth‐20, Ceteareth‐5, and Ceteth‐10. To identify the liquid crystalline phases, the emulsions were analyzed by polarized light microscopy. The physical stability was evaluated by rheology and zeta potential analysis. All emulsions presented lamellar liquid crystal structures. Results showed that this type of surfactant is able to produce liquid crystal in the system, with slight difference in appearance, influencing the physical stability, according to the methods applied.     

Determination of delta 9-tetrahydrocannabinol in pharmaceutical vehicles by high-performance liquid chromatography

A procedure for the determination of delta 9-tetrahydrocannabinol (delta 9-THC) in the presence of its degradation products in pharmaceutical vehicles by high-performance liquid chromatography (HPLC) is described. The method compares favorably with a standard gas-liquid chromatographic procedure used for the analysis of delta 9-THC in sesame oil USP. The HPLC method is suitable for quantitating delta 9-THC in the presence of several pharmaceutical vehicles and excipients including: sesame oil USP, polyvinylpyrrolidone, Emulphor EL620 and Cremophor EL. Extractions are not required and samples require little preparation. Only the addition of an internal standard in an appropriate solvent is necessary before injection. The procedure has been applied to stability studies of delta 9-THC in various pharmaceutical vehicles.     

单一非离子表面活性剂制备胶质气体泡沫的稳定性

用单一的十二烷基醇聚氧乙烯醚(C12EOn)非离子表面活性剂制备了稳定的胶质气体泡沫(CGA). 采用偏光显微镜和流变仪对其表面活性剂溶液相态和泡沫体系的微观结构及流变行为进行研究, 以探索CGA的稳定化机理. 实验结果表明, 分别由C12EO3和C12EO5制备的CGA分散体系中均存在层状液晶相, 层状液晶吸附在气泡的界面上. CGA稳定性可达20 h以上, 没有明显的相分离发生. 而分别由C12EO7和C12EO9制备的CGA呈现由胶束组成的连续相, 不存在液晶相结构, 因而其稳定性较差, 仅能维持数分钟. 实验结果表明, 层状液晶相结构可以显著提高CGA的稳定性. 其稳定作用的机理是通过影响泡沫排液过程, 增强Gibbs-Marangoni效应, 从而提高气泡液膜强度和减缓气相扩散速率.     

Perpendicular and lateral equations of state in layered systems of amphiphiles

For colloidal solutions containing any type of surfactant inducing the formation of locally flat interfaces, we show here that two equations of state are required to understand phase behaviour and stability: the perpendicular and the lateral equations of state. This applies to lamellar phases, locally lamellar connected or sponge phases, uni- and multilamellar vesicle phases formed by detergents, lipids, extractants and theta-shaped molecules in all solutions showing optical anisotropy.     

"Sponge" nanoparticle dispersions in aqueous mixtures of diglycerol monooleate, glycerol dioleate, and polysorbate 80

Lipid nanoparticles of nonlamellar lyotropic phases have a wide solubilizing and encapsulating spectrum for a range of substances thanks to their nanostructured interior featuring both lipophilic and hydrophilic domains. As a consequence, these systems have emerged as promising drug delivery systems in various pharmaceutical and diagnostic applications. Here we present the phase behavior and dispersion properties of a novel three-component lipid system composed of diglycerol monooleate (DGMO), glycerol dioleate (GDO), and polysorbate 80 (P80) which shows several advantageous features relating to drug delivery applications including: spontaneous dispersion formation with a narrow size distribution and tunable particle phase-structure. The obtained phase diagram shows the presence of lamellar (L(alpha)), hexagonal (H(2)), and reverse bicontinuous cubic (V(2)) liquid crystalline phases and an inverse micellar (L(2)) solution. A particularly interesting observation is the presence of a phase region where two liquid phases coexist, most likely the L(2) and L(3) ("sponge phase"). These two phase structures appear also to coexist in the submicron particles formed in the dilute water region, where the L(3) element appears to stabilize nanoparticles with inner L(2) structure. Increasing the fraction of the dispersing P80 component results in the growth of the more water rich L(3) "surface phase" at the expense of the size of the inner L(2) core.     

Compatibility study between ibuprofen and excipients in their physical mixtures

The thermal techniques of analysis were used to assess the compatibility between ibuprofen (IB) and some excipients used in the development of extended released formulations. This study is a part of a systematic study undertaken to find and optimizes a general method of detecting the drug–excipient interactions, with the aim of predicting rapidly and assuring the long-term stability of pharmaceutical product and speeding up its marketing. The thermal properties of IB and its physical association as binary mixtures with some common excipients were evaluated by thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry. FT-IR spectroscopy and X-ray powder diffraction (XRPD) were used as complementary techniques to adequately implement and assist in interpretation of the thermal results. Based on their frequent use in preformulations nine different excipients: starch; microcrystalline cellulose (PH 101 and PH 102); colloidal silicon dioxide; lactose (monohydrate and anhydre); polyvinylpyrrolidone; magnesium stearate and talc were blended with IB. The samples were prepared by mixing the analyte and excipients in a proportion of 1:1 (w:w). The TG/DSC curves of the IB have shown a single stage of mass loss between 175 and 290 °C, respectively, an endothermic peak at 78.5 °C, which corresponds to the melting (literature T _m = 75–78 °C).     

Synthesis of inorganic gels in a lyotropic liquid crystal medium. I. Synthesis of silica gels in lamellar phases obtained from non-ionic surfactants

Some lamellar phases made with aqueous lyotropic liquid crystals were used as templates for the gelation of a silica inorganic network from tetramethylorthosilicate (TMOS). The aim was to synthesize materials with an anisotropic texture.Lamellar phases were obtained by using non-ionic surfacants. At first, structural, textural and rheological properties of the lamellar phases were studied. Then, the evolution of the system after introduction of the alkoxide, i.e., during the sol-gel transition, was followed by low angle X ray diffraction and rheological measurements. Finally, a textural study of dried gels was carried out.The formation of gels with a lamellar structure was analysed by compressing the total phase diagram (quaternary system) to a ternary system. The hydrolysis and condensation reactions of the TMOS are strongly influenced by the presence of the structured lamellar phase. Gelation seems to happen around the liquid crystal microdomains. A schematic model of gelation is proposed based on experimental observations.     

Physicochemical Characterization and Rheological Behavior Evaluation of the Liquid Crystalline Mesophases Developed with Different Silicones

This article presented physicochemical characterization and rheological behavior evaluation of the liquid crystalline mesophases developed with different silicones. There were prepared 5 ternary systems, which were carried out the determination of the relative density, the electric conductivity and polarized light microscopy analysis, being selected two systems to promote the Preliminary Stability Tests. The results showed that System 1 obtained the major liquid crystal formation and a higher stability. The temperature influences in the systems stability and phases structure. In hot oven, observed oneself the mixture of lamellar and hexagonal phase, for both systems.     

Analysis and stability of polymorphs in tablets: The case of Risperidone

Identification of the crystal phase of an active pharmaceutical ingredient (API) in a pharmaceutical tablet is of outmost importance since different polymorphs exhibit different physicochemical properties. Furthermore, some of the crystal phases are protected by patents. Identification of Risperidone polymorph A in film coated commercial tablets was attempted using IR spectroscopy, Raman spectroscopy and X-ray powder diffraction (XRPD). The stability of this polymorph through time and during the manufacturing process was also examined. The inability of IR and Raman techniques to identify the presence of polymorph A in the tablets, despite their lower detection limits for Risperidone, left the XRPD as the only technique that could be used for identifying the presence of Risperidone A against the other crystal phases in the presence of the excipients. Polymorph A was proved to be stable during the manufacturing process and after a storage period of 2 years.     

Compatibility study of the acetylsalicylic acid with different solid dosage forms excipients

This study is part of a research project aimed to find and optimize methods by which drug-excipient compatibility can be reliably and quickly assessed. The objective of the present study was to evaluate the compatibility of the acetylsalicylic acid (ASA), an non-steroidal anti-inflammatory drug, with pharmaceutical excipients of common use including diluents, binders, disintegrants, lubricants and solubilising agents. In order to investigate the possible interactions between ASA and eleven excipients differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry analysis completed by Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction were used for compatibility study. The DSC has proven to be, among the selected analytical techniques, the most sensitive and specific in assessing the compatibility. The samples, as physical mixtures, were prepared by mixing the analyte and excipients in a proportion of 1:1 (w:w). On the basis of thermal results (especially DSC), confirmed by FT-IR and X-ray analysis, a possible chemical interaction was found between the ASA with polyvinylpyrrolidone K30 (PVP) and magnesium stearate, respectively a possible physical interaction with colloidal silicon dioxide and stearic acid (Ac. St.).     

Application of multidimensional scaling to preformulation sciences: a discriminatory tool to group microcrystalline celluloses

Pre-formulation studies constitute the first step of any pharmaceutical product development and manufacture. Establishment of a comprehensive library of critical physical, chemical, biological and mechanical properties of all materials used for a formulation can be costly, tedious and time consuming, despite its importance in quality manufacturing management. This study seeks to demonstrate the pharmaceutical application of multidimensional scaling (MDS) by incorporating it as a pre-formulation tool for grouping an expanded range of microcrystalline celluloses (MCC). MDS presents the various MCC grades in two-dimensional space based on their torque rheological properties; thus conferring an extra dimension to the pre-formulation tool to facilitate the visualization of the relative positions of each MCC grade. Through this work, the utility of MDS for expediting pre-formulation studies, in particular, grouping of excipients that are available in different brands and grades can be amply exemplified.     

Preparation and characterization of highly stable lipid nanoparticles with amorphous core of tuneable viscosity

Lipid nanoparticles (LNP) have been designed based on low cost and human-use approved excipients, and manufactured by an easy, robust, and up-scalable process. Fluid colloidal dispersions or gel viscous formulations of highly stable nanoparticles (more than 12 month stability is achieved for some formulations) can be obtained. Their physicochemical properties are studied by Dynamic Light Scattering, Differential Scanning Calorimetry, and NMR. The results picture nanoparticles with a non-crystalline core, which viscosity can be finely tuned by the lipid composition and the temperature. A design of experiments has been used to investigate the limits of the system colloidal stability. The impact of core and surfactant weight fractions have been explored both experimentally and using the design of experiments. The versatility of this physicochemical system could open the way to a wide range of future pharmaceutical applications.     

Structural characterization and in vivo evaluation of retinyl palmitate in non-ionic lamellar liquid crystalline system

Carrier systems for lipophilic drugs, such as the liquid crystalline systems (LCS) have been extensively studied to improve effect and selectivity. Retinyl palmitate (RP) is widely used in pharmaceutical and cosmetics products to improve the skin elasticity. The aim of this study was the development, characterization and the in vivo effectiveness of RP in non-ionic LCS structures. LCS containing polyether functional siloxane as oil phase, silicon glycol copolymer as surfactant and water in the ratio 30:10:60, with and without RP were studied. The results of the polarized light microscopy, small-angle X-ray scattering and rheology analysis indicated the presence of typical LCS structures with lamellar arrangement. Regardless of the presence of RP, the rheological studies showed the pseudo plastic behavior of the systems. However, highest hysteresis area was verified when comparing the system in the presence and in the absence of RP. Stability study SAXS monitored, carried out up to 30 days in various storage temperature conditions (25±2 °C, 37±2 °C and 5±2 °C) demonstrated the great structural stability of the LCS systems. The in vivo effectiveness analysis suggests that the RP-loaded LCS provided a significant reduction of the orbicular wrinkles in human volunteers (P=0.048).     

Suppression of Liquid-Liquid Phase Separation and Aggregation of Antibodies by Modest Pressure Application

The high colloidal stability of antibody (immunoglobulin) solutions is important for pharmaceutical applications. Inert cosolutes, excipients, are generally used in therapeutic protein formulations to minimize physical instabilities, such as liquid–liquid phase separation (LLPS), aggregation and precipitation, which are often encountered during manufacturing and storage. Despite their widespread use, a detailed understanding of how excipients modulate the specific protein-protein interactions responsible for these instabilities is still lacking. In this work, we demonstrate the high sensitivity to pressure of globulin condensates as a suitable means to suppress LLPS and subsequent aggregation of concentrated antibody solutions. The addition of excipients has only a minor effect. The high pressure sensitivity observed is due to the fact that these flexible Y-shaped molecules create a considerable amount of void volume in the condensed phase, leading to an overall decrease in the volume of the system upon dissociation of the droplet phase by pressure already at a few tens of to hundred bar. Moreover, we show that immunoglobulin molecules themselves are highly resistant to unfolding under pressure, and can even sustain pressures up to about 6 kbar without conformational changes. This implies that immunoglobulins are resistant to the pressure treatment of foods, such as milk, in high-pressure food-processing technologies, thereby preserving their immunological activity.     

Light-sensitive lamellar phases

Light sensitive lamellar (L(alpha)) phases have been generated in glycerol/water mixtures from blends of an inert ABA tri-block co-polymer (dimethylsiloxane-polyethylenoxide, (EO)(15)-(PDMS)(15)-(EO)(15)), and a photodestructible anionic surfactant C(6)PAS (sodium 4-hexylphenylazosulfonate). These L(alpha) systems have been formulated in a 6/4 glycerol/water (v/v) mixed solvent. Rheology, small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS) and dynamic light scattering (DLS) have been used to characterize the change in phase behavior and structure after the incorporated C(6)PAS is selectively degraded by UV light incident on the L(alpha) phases. The ABA co-polymer alone forms weakly structured lamellar mesophases, which are stabilized by thermal fluctuations and characterized by low shear moduli (L(alpha) phase-A). Addition of C(6)PAS (10 mM) introduces charge stabilization, generating more ordered and stiffer L(alpha) systems (L(alpha) phase-B). After UV irradiation (Hg lamp) of the L(alpha)-B phases, and subsequent degradation of the ionic C(6)PAS, the results of rheological and scattering studies are consistent with an irreversible change back to L(alpha) phase-A type systems. These formulations display a novel transition between electrostatically- and thermally-stabilized lamellae, which may be controlled by incident UV light.     

Compatibility studies of trioxsalen with excipients by DSC,DTA, and FTIR

Psoralens are widely used for the treatment of psoriasis. Trioxsalen is a drug prescribed low-dose, belonging to the group of substituted psoralen. The aim of this study was to evaluate the compatibility of trioxsalen with pharmaceutical excipients used in the solid forms by analytical techniques. Binary mixtures between the trioxsalen and pharmaceutical excipients (namely, magnesium stearate, α-lactose, microcrystalline cellulose 102, pregelatinized starch, mannitol, sodium lauryl sulfate, sodium starch glycolate, and croscarmellose sodium) were examined. The trioxsalen–sodium lauryl sulfate mixture displayed some physical interaction based on the DTA and DSC results, but the FTIR study ruled out any chemical change.     

Thermal characterization of antimicrobial drug ornidazole and its compatibility in a solid pharmaceutical product

The ornidazole drug substance presents melt at approximately 90 °C (∆T = 85–98 °C), which is critical for its use on pharmaceutical manufacturing process. This work aimed the thermal characterization of ornidazole raw-material synthesized by three different manufacturers from India, China, and Italy, using the thermoanalytical techniques of DTA, DSC, and TG, besides the verification of its stability and compatibility as a solid pharmaceutical product by the analysis of its binary mixtures (BM) with excipients and a tablet formulation. The characterization includes the thermal decomposition kinetic investigation by Ozawa model using Arrhenius equation and drug purity determination by Van’t Hoff equation. The DSC purity determination and precision were compared with results from UV–Vis spectrophotometric and liquid chromatography, showing an adequate correlation before being recommended as a general method for purity assay. The drug raw-materials presented similar quality and zero-order kinetic behavior, besides showing differences on thermal stability. The drug presented compatibility with the tested excipients since the BM studied presented melting at the same temperature range as the drug and a decomposition temperature similar to the drug for two of the BM, and at a higher temperature for the others three of the BM evaluated, which presented excipients with higher molecular structure, capable of spatial coating on the small drug molecule promoting a physical interaction pharmaceutical acceptable. The tablet was processed by wet granulation and compressed under normal conditions of pressure and temperature, maintaining the physical properties of solid drug approving the manufacturing process used. In this study, the thermal analysis was used with success as an alternative method to characterize, quantify, and perform a preformulation study.