Influence of emulsifier concentration on partition behavior and chemical stability of betamethasone dipropionate in emulsion gels

Puschmann, Julia; Herbig, Michael E.; Müller‐Goymann, Christel C.

doi:10.1016/j.ijpharm.2019.02.044

Cited by 5 publications

(6 citation statements)

References 24 publications

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“…The global food emulsifier market is expected to reach 933,400 tons by 2018 because of the increasing demand for emulsifiers (49). Emulsifiers are a class of compounds that make a mixed liquid of two or more incompatible components (50) and are ubiquitously applied in the manufacture and processing of food, pharmaceuticals, and cosmetics (51). Epidemiological studies found that the incidence of autoimmune diseases has risen concerning the disruption of intestinal tightness with the increased application of industrial food additives, especially emulsifiers (49).…”

Section: Discussionmentioning

confidence: 99%

Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood

Jin

Tang

et al. 2021

mSystems

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Early life events can lead to multiple diseases in adulthood. Previous studies suggested that polysorbate 80 (P80) as a widely used emulsifier in pharmaceutical formulations and food industries could impair the intestinal barrier. However, whether maternal P80 (MP80) exposure could affect the long-term health of offspring remains unknown. In this study, we found that maternal P80 intake could retard intestinal development, disrupt the intestinal barrier, and cause low-grade intestinal inflammation in 3-week-old offspring. 16S rRNA sequencing and correlation analysis revealed that Mucispirillum, Clostridium XI, and Parabacteroides, which positively correlated with intestinal proliferation and differentiation, were decreased in the maternal P80 group. Interestingly, the increase in some harmful bacteria, including Proteobacteria, Helicobacteraceae, Campylobacterales, and Desulfovibrionales, persisted from the weaning period to adulthood (3 to 8 weeks). Furthermore, a fecal microbiota transplantation assay showed that the mice gavaged with feces from 3-week-old offspring of the MP80 group presented more severe intestinal inflammation and barrier disruption than the mice that received feces from the offspring of the control group. Finally, maternal P80 intake remarkably aggravated the structural disorder of intestinal crypt, increased proinflammatory factors, and exacerbated dextran sulfate sodium (DSS)-induced colitis in adulthood. Conclusively, maternal P80 intake could induce gut dysbiosis and promote colitis susceptibility in adulthood. This study provides new insights into the prevention of inflammatory bowel disease (IBD). IMPORTANCE The main findings of this research showed that maternal P80 intake could disrupt the intestinal barrier, induce gut dysbiosis, and promote colitis susceptibility in adulthood. This study will enhance understanding of the prevention of IBD.

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Section: Discussionmentioning

confidence: 99%

Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood

Jin

Tang

et al. 2021

mSystems

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“…Partitioning of the preservative into the oil phase can result in loss of preservative efficacy, the composition of the oil phase can have a big impact on this phenomenon as illustrated by (Herbig et al, 2023), where phenoxyethanol was observed to preferably partition into oil phases containing medium chain triglycerides. Similarly, the levels of surfactants can impact the partitioning behaviour of APIs and excipients, this is particularly relevant for lipophilic APIs sensitive to hydrolysis, for example Betamethasone, as increasing partitioning into the aqueous phase can impact the chemical stability of the formulation (Puschmann et al, 2019).…”

Section: Downloaded Frommentioning

confidence: 99%

Topically Applied Therapies for the Treatment of Skin Disease: Past, Present, and Future

Brown,

Williams,

Chilcott

et al. 2024

Pharmacol Rev

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“…In addition, for consistency agent stabilized formulation, process parameters often have a strong impact on product quality [ 29 , 30 ], which can make scaleup cumbersome. It has been shown that creams based on polymeric thickeners can be stabilized with less than 0.2% hydrophilic emulsifiers and can be better understood in terms of API saturation and distribution [ 31 , 32 ]. Therefore, apart from cases where the specific sensorial properties of consistency agent stabilized creams are desired, polymer-thickened alternatives can be typically more rationally designed, upscaled, and controlled.…”

Section: Status-quo Of Semi-solid Formulations In Recently Approved P...mentioning

confidence: 99%

“…By decreasing the degree of saturation, an initially too-high skin penetration profile could be well-matched to that of the Protopic ® ointment [ 32 ]. For betamethasone dipropionate, a decrease in saturation during the transformation of the vehicle led to lower skin penetration as compared to formulations where the saturation did not significantly change [ 31 ].…”

Section: Formulation Designmentioning

confidence: 99%

“…With the addition of increasing concentrations of the hydrophilic solvent PEG400 to the water phase, the distribution from MCT to water increases ( Figure 1 ). For hydrolysis-prone APIs, a strong partitioning into the oil phase is a physical means of improving chemical stability, as shown for betamethasone dipropionate and tacrolimus [ 31 , 32 ]. Apart from the design of the oil phase, also minimizing the excess concentration of the hydrophilic emulsifier plays an important role in this.…”

Section: Formulation Designmentioning

confidence: 99%

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Rational Design of Topical Semi-Solid Dosage Forms-How Far Are We?

Herbig¹,

Evers²,

Gorissen³

et al. 2023

Pharmaceutics

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Specific aspects of semi-solid dosage forms for topical application include the nature of the barrier to be overcome, aspects of susceptibility to physical and chemical instability, and a greater influence of sensory perception. Advances in understanding the driving forces of skin penetration as well as the design principles and inner structure of formulations, provide a good basis for the more rational design of such dosage forms, which still often follow more traditional design approaches. This review analyses the opportunities and constraints of rational formulation design approaches in the industrial development of new topical drugs. As the selection of drug candidates with favorable physicochemical properties increases the speed and probability of success, models for drug selection based on theoretical and experimental approaches are discussed. This paper reviews how progress in the scientific understanding of mechanisms and vehicle-influence of skin penetration can be used for rational formulation design. The characterization of semi-solid formulations is discussed with a special focus on modern rheological approaches and analytical methods for investigating and optimizing the chemical stability of active ingredients in consideration of applicable guidelines. In conclusion, the combination of a good understanding of scientific principles combined with early consideration of regulatory requirements for product quality are enablers for the successful development of innovative and robust semi-solid formulations for topical application.

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Influence of emulsifier concentration on partition behavior and chemical stability of betamethasone dipropionate in emulsion gels

Cited by 5 publications

References 24 publications

Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood

Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood

Topically Applied Therapies for the Treatment of Skin Disease: Past, Present, and Future

Rational Design of Topical Semi-Solid Dosage Forms-How Far Are We?

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