Chapter 3 - Methods for nanoencapsulation

Effects of high-speed homogenization and high-pressure homogenization on structure of tomato residue fibers

Spray drying is one of the most commonly used manufacturing techniques for amorphous solid dispersions (ASDs). During spray drying, very fast solvent evaporation is enabled by the generation of small droplets and exposure of these droplets to a heated drying gas. This fast solvent evaporation leads to an increased viscosity that enables kinetic trapping of an active pharmaceutical ingredient (API) in a polymer matrix, which is favorable for the formulation of supersaturated, kinetically stabilized ASDs. In this work, the relation between the solvent evaporation rate and the kinetic stabilization of highly drug-loaded ASDs was investigated. Accordingly, thermal gravimetric analysis (TGA) was employed to study the evaporation kinetics of seven organic solvents and the influence of solutes, i.e., poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), fenofibrate (FNB), and naproxen (NAP), on the evaporation behavior. At 10 °C below the boiling point of the respective solvent, methanol (MeOH) had the lowest evaporation rate and dichloromethane (DCM) had the highest. PVPVA decreased the evaporation rate for all solvents, yet this effect was more pronounced for the relatively faster evaporating solvents. The APIs had opposite effects on the evaporation process: FNB increased the evaporation rate, while NAP decreased it. The latter might indicate the presence of interactions between NAP and the solvent or NAP and PVPVA, which was further investigated using Fourier transform-InfraRed (FT-IR) spectroscopy. Based on these findings, spray drying process parameters were adapted to alter the evaporation rate. Increasing the evaporation rate of MeOH and DCM enabled the kinetic stabilization of higher drug loadings of FNB, while the opposite trend was observed for ASDs of NAP. Even when higher drug loadings could be kinetically stabilized by adapting the process parameters, the improvement was limited, demonstrating that the phase behavior of these ASDs of FNB and NAP immediately after preparation was predominantly determined by the API-polymer-solvent combination rather than the process parameters applied.

Application of supercritical fluid technology for solid dispersion to enhance solubility and bioavailability of poorly water-soluble drugs

In this study, the anhydrous lipstick base was designed to incorporate with water. The additional water was formulated and prepared into the nanoscale water in oil (w/o) emulsions before mixed with the lipstick base to form w/o nanoemulsion lipsticks. The formulation parameters that are likely to affect the physicochemical properties of lipsticks were evaluated. These parameters included type of emulsifiers as well as dose of water and emulsifiers. The studied nanoemulsions composed of water, isopropyl myristate, mineral oil and PEG-30 dipolyhydroxystearate was prepared in the high speed homogenizer following with the high pressure homogenizer at 500 bars for 3 cycles. The final w/o nanoemulsions with different doses of water and emulsifiers were separately incorporated into the lipstick base. The conventional w/o emulsions with the same formulas that were prepared by the high speed homogenizer at 1000 rpm for 10 min were compared in parallel. The mean particle size, size distribution, stability and physicochemical properties in terms of hardness and spreading ability were operated. Results revealed the water content significantly affected to the hardness of w/o nanoemulsion lipsticks whereas the emulsifier did not. Additionally, the particle size of the preparations also affected to the hardness of lipsticks.

Red palm oil (RPO) comes from the mesocarp of the palm fruit (Elaeis guineensis Jacq.) which is rich in carotenoids, vitamin E, and fatty acids. The use of RPO in pharmaceutical formulations poses challenges related to stability, oxidation susceptibility, and consumer acceptance due to its distinctive aroma and taste. To address these limitations, a variety of innovative formulation strategies, including emulsification, nanoemulsification, microencapsulation, and lipid-based systems have been researched. The RPO formulation aims to improve stability, bioavailability, and enhance therapeutic effects. Manufacturing techniques such as high-pressure homogenization, spray drying, and encapsulation of supercritical fluids have stabilized the bioactive components of RPO, minimizing oxidation, and controlling continuous release. Nanoemulsions and lipid nanoparticles have shown results in a wide range of applications from topical antioxidants to systemic drug delivery, by utilizing the synergistic effects of the lipophilic properties of RPO with other active ingredients. In addition, encapsulation technology has improved the stability of RPO storage, thereby expanding its usefulness in nutraceuticals and multivitamin supplements. This article also aims to bridge the research gap related to RPO formulation and provide insights into optimizing RPO formulations for broader benefits in health and disease management. The use of RPO in the future perspective is focused on nanotechnology formulations to improve solubility, stability, bioavailability, and support targeted and controlled drug delivery.

Abstract: This review article constitutes an introductory report on nanotechnology focusing on the various manufacturing approaches of nanocrystals. Nanocrystals are a solid form to tackle the issue identified with poor fluid solvency. Hence, it is a useful technique in improving the bioa-vailability of various poorly soluble drugs. On a broader way, nanocrystal technology is mainly classified as top-down technology, bottom-up technology and a combination of top-down and bottom-up technology. Top-down technology is based on the principle of breaking down a com-plex into small crystals. This process is executed by using high-pressure homogenization, laser ablation, media mills, ultrasound technology, vacuum dissolution, gas condensation and mechani-cal attrition. Bottom-up technology is based on the principle of preparation by gathering at-oms/molecules together. It is achieved by using precipitation, supercritical fluid, gel-gel technol-ogy, spray drying, hydrolysis, and condensation. Due to the diverse characteristics and properties of drugs, a combination of top-down and bottom-up techniques is best for manufacturing nano-crystals. Some of the promising technique includes nano-edge technology and smart-crystal tech-nology. These techniques are discussed in this review.

Extra virgin olive oil-in-water nanoemulsions stabilised with synthetic or clean label surfactants (Tween 20 or soy lecithin) was prepared using high-pressure homogenisation (HPH). The effect of HPH pressure and the number of cycles were assessed through response surface methodology to optimise homogenisation processing parameter. Mean droplet diameter (MDD), polydispersity index (PDI), thermal stability and oxidation stability of the resulting emulsions were evaluated. The results showed that the formation and stability of nanoemulsions can be affected by the homogenisation processing parameters (pressure and cycles) and the properties of surfactants (interfacial tension, viscoelasticity and molecule structure). Although MDD and PDI of Tween 20 stabilised nanoemulsions were influenced by homogenisation pressure and cycles, there was not a significant effect on lecithin-stabilised nanoemulsions. A homogenisation pressure of at least 400 bars produced Tween 20 stabilised nanoemulsion (MDD < 200 nm), whereas lecithin-stabilised nanoemulsion were obtained after high-speed homogenisation without using HPH. HPH at 400 bars for 1 cycle produced nanoemulsions with greater physical stability when using either Tween 20 or lecithin. Tween 20 stabilised nanoemulsion showed significantly higher (p < 0.05) thermal stability and lipid oxidative stability than lecithin-stabilised nanoemulsion. Following an optimisation study using regression modelling, the optimal homogenisation parameter for MDD of Tween 20 stabilised emulsion was found at pressure of 764 bars with 1 cycle, while lecithin-stabilised emulsion was found at pressure of 3 bars with 2 cycles. Overall, this study has important implications for optimising nanoemulsion production for potential application in the food industry.

The factors that influence product development depend, amongst other things, on the type of product, the economic situation, the state of the art technology and various social and cultural trends. In modern era, often not the specs and costs are the decisive factors for purchasing a product, but aspects like design and brand personality. One of the reasons for this is the abundance of products of the same type for the same purpose. In fact, this is the current situation for dry powder inhalers (DPIs) although the self-congruity concept seems more applicable to the doctors who prescribe the inhalers than to the patients who are using them. For the early DPIs from the 1960s and 1970s the driving factor for development was the necessity of having an alternative for cholofluorocarbon (CFC) containing metered dose inhalers (MDIs). An important factor affecting their design could have been the desire to improve pulmonary drug delivery compared to that from MDIs, but unfortunately this oportunity was missed. Instead, available technology like hard gelatin capsules and adhesive ('ordered') mixtures were used and lung deposition remained more or less the same as from MDIs (only approx. 10% of the dose). After the capsule (and multi-dose reservoir) DPIs became more widely accepted and patents on inhaled drugs expired, consulting groups and generic manufacturers became more and more involved in the emerging DPI market, purely on an economic basis. This does not mean that there have not been developments yet aiming at improvement of the therapy with DPIs and various future applications may give a new boost to using new technology for dry powder inhalation.

The nanoparticle albumin bound™ (nab™) technology generally offers great potential for the formulation of poorly water-soluble drugs as albumin-stabilized nanosuspensions for intravenous use while avoiding solubilizers and cross-linking agents. The nab™ technology is a three-step process consisting of emulsification, high-pressure homogenization and solvent evaporation.Within this work, a screening approach was developed to predict whether active pharmaceutical ingredients are suitable for nab™ formulations. A design of experiments approach was used to investigate the effects of ultrasonic homogenization on an albumin-stabilized itraconazole nanosuspension. Based on this, a screening platform was developed, and subsequently evaluated and applied to a selection of poorly water-soluble drugs. The screening process to produce albumin-stabilized nanosuspensions consists of two process steps: Ultrasonic treatment, which combined emulsification and homogenization, followed by solvent evaporation. The results of the screening process were fully transferable to the standard three-step process of nab™ technology. In addition, based on drug screening, drug properties were highlighted that are important for the development of nab™ formulations.All in all, the nab™ technology is a promising but not universal formulation platform for poorly water-soluble drugs. Nevertheless, for some poorly soluble drugs it offers a valuable approach for the formulation of nanosuspensions for intravenous use.

Nanoencapsulation is an attractive novel technique used for incorporating essential oils in food preparations and pharmaceutical formulae. This study investigated the effect of nanoencapsulation on the composition of volatile compounds, as well as the antioxidant and anticancer activities of hydrodistilled (HD) Origanum glandulosum Desf. Oil, which was encapsulated into nanocapsules via High Speed Homogenization (HSH) and into nanoemulsions through High Pressure Homogenization (HPH). Thirty-two volatile components were identified using Gas Chromatography-Mass Spectrometry analysis (GC-MS) in HD essential oil representing 99.04% of the total oil content. GC-MS analysis showed that the use of HPH to prepare nanoemulsions negatively affected the active compounds present in HD oil, particularly carvacrol and thymol, whereas the use of HSH led to significant quantitative differences in the composition of volatiles between HD oil and nanocapsules but generated the same profile. Consistent with the differences in total phenolics, total flavonoids, and volatiles identified in HD and nanoparticles, HD essential oil exhibited a higher antioxidant activity (IC50 4.22 mg/mL) than nanocapsules (IC50 57.51 mg/mL) and nanoemulsion (IC50 78.50 mg/mL), while nanocapsules showed the strongest cytotoxic effect on liver cancer cell line Hep-G2 (54.93 μg/mL) in comparison to HD oil (73.13 μg/mL) and nanoemulsions (131.6 μg/mL).

Supercritical fluid (SCF)-assisted fabrication of carrier-free drugs: An eco-friendly welcome to active pharmaceutical ingredients (APIs).

Microencapsulation, a crucial technique in the field of pharmaceutical science, involves enclosing active pharmaceutical ingredients (APIs) within microspheres, microcapsules, or microparticles. This study systematically explores the various facets of microencapsulation, encompassing its definition, advantages, disadvantages, methodologies, and diverse applications in the pharmaceutical sector. The definition section delves into the fundamental concept microencapsulation, elucidating of the process that protects APIs within a protective matrix. The research uncovers advantages such as improved drug stability, extended release, enhanced bioavailability, and minimized side effects. Concurrently, it critically examines potential drawbacks, including formulation challenges and scalability issues, providing a comprehensive perspective to optimize pharmaceutical applications. Methodologically, the study thoroughly reviews different microencapsulation techniques like spray drying, coacervation, and solvent evaporation. An evaluative analysis of their merits and limitations is presented, providing insights crucial for tailoring microencapsulation processes to specific drug characteristics and therapeutic requirements. The extensive realm of microencapsulation applications in pharmaceuticals is explored, ranging from controlled drug delivery and targeted therapy to taste masking and protecting sensitive compounds. The research meticulously scrutinizes these diverse applications, highlighting transformative potential the of microencapsulation in drug development and delivery. Through an in-depth analysis of microspheres, microcapsules, and microparticles, this research contributes valuable insights into their unique properties and applications in pharmaceutical formulations. The ultimate goal of this book chapter is to investigate the advance drug delivery systems, paving the way for more effective and patient friendly pharmaceutical products. This comprehensive resource aims to benefit researchers, pharmaceutical scientists, and industry professionals, enhancing their understanding of microencapsulation's pivotal role in shaping the future of pharmaceutical science.

Spray drying the Pickering emulsions stabilized by chitosan/ovalbumin polyelectrolyte complexes for the production of oxidation stable tuna oil microcapsules

ABSTRACTEthyl cellulose (EC) and Eudragit RL-100 (ERL-100) were used for the preparation of sustained released microparticles of mefenamic acid (MFN) by using oil-in-oil (o/o) solvent evaporation as well as spray drying. A Plackett-Burman design was employed using Design-Expert software. The resultant microparticles were characterized for their size, surface morphology, encapsulation efficiency, and drug release. Imaging of microparticles was performed by field emission scanning electron microscopy. The drug and polymer interaction was investigated by Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffractometry (XRPD). The microparticles showed encapsulation efficiency in the range of 29.44 to 89.20% by solvent evaporation and 83.73 to 96.69% by spray drying. The surface of the microparticles was smooth, round, and regular, without any erosion and cracking. The size of the microparticles was found to be in the range of 6.55 to 41.1 µm. FTIR analysis confirmed no interaction of MFN with the polymers. XRPD showed the dispersion of the drug within the microparticle formulation. These results helped in finding the optimum formulation variables for encapsulation efficiency (EE) of microparticles.

Role of solvent in differential phase behavior of celecoxib during spray drying.