: Neratinib maleate (NM), a tyrosine kinase inhibitor, is used in the treatment of breast cancer. Current oral therapy of NM suffers from low and variable bioavailability due to the solubility and permeability-related issues of the drug. To overcome the low oral bioavailability, the drug is recommended to be administered at high doses, causing severe gastrointestinal side effects leading to discontinuation of the drug therapy. : In this work, NM-loaded lipid-polymer hybrid nanoparticles (NM-LPNs) were designed and optimized to improve the oral bioavailability of the drug. A systematic approach involving a screening design followed by an optimization design based on the principles of design of experiments (DoE) was used to prepare NM-LPNs. Minimum particle size (PS) ranging between 200 and 300 nm and maximum drug loading (DL (%)) were set as the target physicochemical properties. The optimized NM-LPNs, with a mean PS of 278.57 ± 21.16 nm and a DL (%) of 25.77 ± 1.11%, were further characterized for physicochemical properties, thermal and diffractometric analysis, stability, in vitro drug release, and oral pharmacokinetic studies. : The nanoparticles exhibited a burst release followed by a prolonged release up to 12 h in the in vitro drug release studies in pH 6.8 media. : The mean C and the AUC values were found to increase significantly for NM-LPNs by 1.72 times ( < 0.01) and 1.58 times ( < 0.01), respectively, when compared to plain NM in the oral pharmacokinetic studies. The optimized NM-LPN formulation can reduce the oral dose of NM and, thereby, its dose-dependent side effects.

The spatial distribution of fat crystals significantly impacts the stability and digestion properties of emulsions. This study investigated the templating effect of monoglycerides in controlling the spatial distribution of solid fat crystallization within double emulsions. Double emulsions were formulated with glyceryl monostearate (GMS), glyceryl monolaurate (GML), glyceryl monooleate (GMO), beeswax (BW), glyceryl distearate (GDS), and glyceryl tristearate (GTS) in the oil phase. Monoglycerides influenced the spatial distribution pattern of BW crystals, while minimally affecting GDS and GTS. Cooling at 4 °C increased interfacial crystallization without altering distribution patterns. Monoglycerides raised the onset and peak crystallization temperatures and enthalpy in BW emulsions, with GMS showing the most significant effects. Adding GMS slowed nucleation rates and extended induction times, promoting interface crystallization. The templating effect also reduced crystal lamellar thickness, facilitating the transition from β-crystalline to β' crystalline in BW. These findings provide insights into selecting crystallizing emulsifiers and enhancing double emulsion stability.

Orally disintegrating granules (ODGs) are a pharmaceutical form commonly used for the administration of NSAIDs because of their easy assumption and fast dispersion. The development of ODGs is not easy for drugs like dexketoprofen trometamol (DXKT), which have a bitter and burning taste. In this work, high-shear coating (HSC) was used as an innovative technique for DKXT taste masking. This study focused on coating DXKT granules using the HSC technique with a low-melting lipid excipient, glyceryl distearate (GDS). The HSC technique allowed for the coating to be developed through the thermal rise resulting from the friction generated by the granules movement inside the equipment, causing the coating excipient to soften. The design of the experiment was used to find the best experimental coating conditions in order to gain effective taste masking by suitably reducing the amount of drug released in the oral cavity. The influence of the granule dimensions was also investigated. Coating effectiveness was evaluated using a simulated saliva dissolution test. It was found that low impeller speed (300 rpm) and a 20% coating excipient were effective in suitably reducing the drug dissolution rate and then in taste masking. The coated granules were characterized for their morphology and solid-state properties by SEM, BET, XRPD, DSC, and NIR analyses. A human taste panel test confirmed the masking of DXKT taste in the selected batch granules.

Polyethylene glycol-23 glyceryl distearate (GDS-23), a diacylglycerol polyethylene glycol adduct, forms niosomes with a liposome-like structure and functions as an active ingredient in drug delivery systems. In addition, it upregulates antioxidant proteins such as heme oxygenase 1 and NAD(P)H-quinone dehydrogenase 1 in cells. However, the activation of nuclear factor E2-related factor-2 (Nrf2), which plays a role in inducing the expression of antioxidant proteins, and its protective effects induced by GDS-23 treatment against oxidative stress have not been elucidated. This study aimed at verifying the activation of Nrf2 by GDS-23 and clarifying its underlying mechanisms, and investigated whether GDS-23 protects against hydroquinone-induced cytotoxicity. Normal human epidermal keratinocytes were treated with GDS-23. Real-time reverse transcription-polymerase chain reaction, western blotting, and immunostaining were used to investigate the mechanism of Nrf2 activation, and neutral red assay was performed to evaluate cytotoxicity. GDS-23-treated cells showed an increase in antioxidant protein levels and stabilization of Nrf2 in the nucleus. During Nrf2 activation, p62, an autophagy-related adaptor protein, was phosphorylated at Ser349. Inhibition of the interaction between the phosphorylated p62 and Kelch-like ECH-associated protein 1 significantly suppressed the GDS-23-mediated induction of antioxidant protein expression. In addition, hydroquinone-induced cell toxicity was significantly attenuated by GDS-23. GDS-23 induced the intracellular antioxidant system by activating Nrf2 in a p62 phosphorylation-dependent manner without generating oxidative stress in the cells. GDS-23 may be applied as a multifunctional material for drug delivery system that enhances internal antioxidant systems.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 2002, along with updated information regarding product types and concentrations of use, and confirmed that these 17 glyceryl diesters are safe as cosmetic ingredients in the practices of use and concentration as described in this report.

The crystallization behavior of commercial mono- and diglycerides (MDG) in paraffin oil is studied to develop an in-depth understanding of the polymorphic transitions useful for the physical stability of petroleum oil-based topical emulsions. Optical microscopy and differential scanning calorimetry measurements showed the formation of plate-like and spherulite crystals at high and low temperatures, in sequence, while cooling a solution of MDG dissolved in oil. High-resolution NMR and X-ray scattering demonstrate that 1-monoglycerides (mixture of 1-glyceride monostearate and 1-glyceride monopalmitate) cocrystallize to an inverse-lamellar structure (L polymorph) that mainly forms plate-like crystals at a higher temperature. The L polymorph is seen to exist up to room temperature during the cooling process. At lower temperatures, 1,3-diglycerides (mixture of 1,3-glyceryl distearate and 1,3-glyceryl dipalmitate) crystallize into β-polymorphs that form spherulites. The spherulites tend to assemble into elongated strands via aggregation, leading to the formation of a percolating network structure. The sizes of both types of crystals decrease with an increasing cooling rate, leading to a higher mechanical modulus due to the increased network connectivity of spherulites. In an emulsion, monoglycerides in the form of L polymorphs having plate-like crystal morphology show a higher affinity to the polar liquid/oil interface, thereby providing better interfacial stability compared to the spherulitic β-polymorphs. However, diglycerides in the form of spherulites form bulk network structures which provide network stabilization to the suspended droplets. This work demonstrates that MDG, a commercially available ingredient that combines the differential functionality of monoglycerides and diglycerides, is an effective, bifunctional, emulsifying agent for petrolatum-based topical emulsions.

Modified Leeming and Notman agar medium (mLNA) has been widely utilized to grow lipophilic fungi belonging to the genus Malassezia. We developed a new artificial-sebum-containing mLNA to obtain higher yields of Malassezia species. The olive oil in mLNA was replaced with an artificial sebum composed of triglyceride (triolein), diglyceride (glyceryl distearate), fatty acids (palmitic acid, myristic acid, pentadecanoic acid, and oleic acid), and squalene. Furthermore, the Tween 60 was replaced with self-emulsifying glyceryl stearate. Nine human-associated Malassezia species grew well on the artificial-sebum-containing mLNA, and the most predominant fungus on human skin, Malassezia restricta, exhibited double wet cell weight in artificial sebum-containing mLNA compared to wet cell weight in standard mLNA.

The digestion behaviour of lipid-based nanocarriers (LNC) has a great impact on their oral drug delivery properties. In this study, various excipients including surfactants, glycerides and waxes, as well as various drug-delivery systems, namely self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were examined via the pH-stat lipolysis model. Lipolysis experiments with lipase and pancreatin revealed the highest release of fatty acids for medium chain glycerides, followed by long chain glycerides and surfactants. Waxes appeared to be poor substrates with a maximum digestion of up to 10% within 60 min. Within the group of surfactants, the enzymatic cleavage decreased in the following order: glycerol monostearate > polyoxyethylene (20) sorbitan monostearate > PEG-35 castor oil > sorbitan monostearate. After digestion experiments of the excipients, SEDDS, SLN and NLC with sizes between 30 and 300 nm were prepared. The size of almost all formulations was increasing during lipolysis and levelled off after approximately 15 min except for the SLN and NLC consisting of cetyl palmitate. SEDDS exceeded 6000 nm after some minutes and were almost completely hydrolysed by pancreatin. No significant difference was observed between comparable SLN and NLC but surfactant choice and selection of the lipid component had an impact on digestion. SLN and NLC with cetyl palmitate were only digested by 5% whereas particles with glyceryl distearate were decomposed by 40-80% within 60 min. Additionally, the digestion of the same SLN or NLC, only differing in the surfactant, was higher for SLN/NLC containing polyoxyethylene (20) sorbitan monostearate than PEG-35 castor oil. This observation might be explained by the higher PEG content of PEG-35 castor oil causing a more pronounced steric hindrance for the access of lipase. Generally, digestion experiments performed with pancreatin resulted in a higher digestion compared to lipase. According to these results, the digestion behaviour of LNC depends on both, the type of nanocarrier and on the excipients used for them.

This study aims to design and characterize Nanostructured lipid carriers (NLC) and Nanostructured lipid carrier-based hydrogels with Passiflora edulis seeds oil, a by-product from Madeira Island food industry. NLC were prepared by the ultrasonication technique, using passion fruit seeds oil as a liquid lipid and glyceryl distearate as a solid lipid. These NLC were then gelled with Poly (acrylic acid). Long-term stability studies were conducted with NLC and NLC-based hydrogels stored for 12 months. The following tests were performed: morphology, encapsulation efficiency, particle size analysis, polydispersity index analysis, zeta potential, pH measurement, color analysis, viscosity studies, texture analysis, in vitro occlusion test, ex vivo skin penetration study, tyrosinase inhibition activity, in vitro skin permeation experiments and in vitro cytotoxicity studies. The developed NLC had spherical shape and narrow particle sizes distribution with mean sizes in the range of 150 nm and PDI below 0.3, Zeta potential values around -30 mV and high Encapsulation efficiency. The tyrosinase inhibitory activity and skin retention of the nanoparticles was superior to that of the non-encapsulated oil. The developed formulations did not show cytotoxicity towards HaCat cells and presented suitable viscosity and texture properties for skin application, proving to be good candidates as depigmenting agent.

Raloxifene (RLX) is a second-generation selective estrogen receptor modulator used to treat osteoporosis in postmenopausal women. RLX fails to be developed into injectable dosage forms due to poor solubility. Although oral formulations are clinically available, the lower bioavailability (<2%) embarrasses the pharmaceutists. This work reported a bioadhesive nanosystem intended for oral delivery of RLX to enhance its oral bioavailability and address the formulation challenge. The bioadhesive nanosystem refers to polymer-lipid hybrid nanoparticles made up of Carbopol 940, glyceryl distearate, and TGPS. RLX was solidly encapsulated into bioadhesive nanoparticles (NPs) through a nanoprecipitation technique along with synchronous desalting of RLX·HCl. The resultant RLX-loaded NPs (RLX-NPs) were characterized by particle size, potential, morphology, and entrapment efficiency. The release and oral bioavailability of RLX-NPs in rats were comparatively investigated with RLX-loaded common lipid nanoparticles (RLX-NPs). The preferred formulation possesses a particle size of 150 nm around with a polydispersity index (PDI) of 0.282. RLX-NPs exhibited slower drug release than RLX-NPs owing to the presence of an adhesive layer. After oral administration, RLX-NPs resulted in significant enhancement in the bioavailability of RLX, up to 556.9% relative to RLX suspensions, while it was merely 244.7% for RLX-NPs. Cellular testing and transport imaging demonstrated that NPs were endowed with excellent intestinal epithelial affinity and absorbability. Our study affords an alternative option for designing a suitable oral delivery system specific to amphiphobic drugs like RLX·HCl.