Simultaneous emulsification and interfacial polycondensation for the preparation of colloidal suspensions of nanocapsules

Sub-micrometric particles having an oil core and a polymer shell (nanocapsules) have been prepared by combining in a single stage the emulsification process and an interfacial polymerization reaction. The spontaneous emulsification produced very fast a dispersion of oil droplets of 100–400 nm mean diameter at the surface of which the subsequent polycondensation reaction took place. The process has been optimized with respect to the choice of α-tocopherol as the oil and made robust regarding the presence of monomers in the aqueous and oil phases and their conversion into polymers. The major cause of troubles was the large concentration of diol or diamine monomers in the aqueous phase that made the oil droplets unstable with respect to aggregation immediately after their formation. Once the emulsifier has adsorbed and the polymerization has completed, the final suspensions of nanocapsules were quite stable over long periods. A secondary population of micrometric particles that coexisted with the nanocapsules was present in several cases, which was unfavourable regarding their application as a drug delivery system for cosmetic applications.     

Preparation and Characterization of Spray-Dried Polymeric Nanocapsules

Recently, much interest has been generated by colloidal drug delivery systems such as nanocapsules because of the possibilities for controlled release, increased drug efficacy, and reduced toxicity after parenteral administration. Nanocapsules of poly-ε-caprolactone and Eudragit S90® were prepared. However, these systems present physicochemical instability. To dry these nanocapsule suspensions with the view of obtaining a solid form, the spray-drying process was used. Spray-dried powders of nanocapsules of poly-ε-caprolactone and Eudragit S90® were prepared by atomization in a Büchi 190 Mini-spray dryer using colloidal silicon dioxide as a technological carrier. The morphological analysis of the surface at the powders showed that nanocapsules remain intact, and no change in particle size was detected after the spray-drying process. These results suggest that this method can be an interesting alternative to dry nanocapsule suspensions.     

Pharmaceutical formulation and manufacturing using particle/powder technology for personalized medicines

Particle/powder technology is used in the manufacture of many pharmaceutical products, and research on the physical properties of particles in the nano- to micro-particle range is important in the pharmaceutical field. The concept of precision medicine will require an increasing shift in pharmaceutical manufacturing toward the design of individualized products. This perspective article focuses on particle design and powder technology for advanced formulations that will be needed in the future for individualized drug formulations and on-demand production. Nanoparticles as drug carriers in drug delivery systems will require particle designs to meet the treatment requirements of individual patients with a particular disease. In pharmaceutical manufacturing, process intensification, such as continuous manufacturing and integrated drug production from drug synthesis to final formulation, has attracted increased attention. Digital design approaches, such as artificial intelligence based on computer-aided development, also will be increasingly used. Continuous production of pharmaceutical products enables downsizing of manufacturing equipment, and on-demand manufacturing equipment has been developed. In addition, additive manufacturing, such as 3D printing, is considered to be suitable for personalized formulations, and small-scale powder handling and predictive modeling of powder characterization will be important for individual preparations.     

Preparation and characterization of spray-dried polymeric nanocapsules

Recently, much interest has been generated by colloidal drug delivery systems such as nanocapsules because of the possibilities for controlled release, increased drug efficacy, and reduced toxicity after parenteral administration. Nanocapsules of poly-epsilon-caprolactone and Eudragit S90 were prepared. However, these systems present physicochemical instability. To dry these nanocapsule suspensions with the view of obtaining a solid form, the spray-drying process was used. Spray-dried powders of nanocapsules of poly-sigma-caprolactone and Eudragit S90 were prepared by atomization in a Büchi 190 Mini-spray dryer using colloidal silicon dioxide as a technological carrier. The morphological analysis of the surface at the powders showed that nanocapsules remain intact, and no change in particle size was detected after the spray-drying process. These results suggest that this method can be an interesting alternative to dry nanocapsule suspensions.     

Tablets containing drug-loaded polymeric nanocapsules: an innovative platform

The aim of the present work was to evaluate the feasibility to convert drug-loaded nanocapsule suspensions in a solid dosage form (tablets). Dexamethasone was used as a model drug due to its low aqueous solubility and fast drug release from conventional tablets. Granules containing dexamethasone-loaded nanocapsules were obtained by a wet granulation process using a dispersion of polyvinylpirrolidone/nanocapsules as a binder system. Granules were compressed in an eccentric compression machine (D-NC-T). A control formulation (tablets without nanocapsules) was also prepared (D-T). Tablets were characterized by means of mean weight, hardness, friability, diameter, thickness, disintegration time, drug content, morphological analysis by scanning electron microscopy (SEM), and in vitro drug release studies. D-NC-T showed adequate physicochemical characteristics according to the pharmacopeial requirements in terms of mean weight, hardness, friability, disintegration time and drug content. Intact nanocapsules in tablets were observed by SEM. In vitro drug release studies showed a slower release of dexamethasone from these tablets (D-NC-T) compared to the control formulation (D-T). Results showed that these tablets represent an interesting platform to the development of oral drug delivery systems containing polymeric nanocapsules.     

A new process for drug loaded nanocapsules preparation using a membrane contactor

In this paper, we describe a new process for the preparation of drug loaded nanocapsules using a membrane contactor which may be scaled up for industrial applications. Nanocapsules are prepared according to the nanoprecipitation method. The organic phase (solvent, polymer, oil, and drug) is pressed through the pores of an ultrafiltration membrane via the filtrate side. The aqueous phase (water and surfactant) circulates inside the membrane module, and sweeps away the nanocaspules forming at the pore outlets. Two model drugs are selected for the preparation of drug loaded nanocapsules: indomethacin and vitamin E. It is shown that indomethacin loaded nanocapsules with a mean diameter of 240 nm and vitamin E loaded nanocapsules with a mean diameter of 230 nm are obtained with a 150,000 daltons ultrafiltration membrane, a transmembrane pressure of 3 bar, and a crossflow rate of 1.7 m.s(- 1). High fluxes are also obtained (around 0.6 m3/h.m2), leading to the preparation of 1.8 10(- 3) m3 drug loaded nanocapsules in 8 min. The advantage of this membrane contactor compared to other processes for drug loaded nanocapsules preparation is shown to be its scale-up ability.     

Ultrastable Liquid–Liquid Interface as Viable Route for Controlled Deposition of Biodegradable Polymer Nanocapsules

Liquid–liquid interfaces are highly dynamic and characterized by an elevated interfacial tension as compared to solid–liquid interfaces. Therefore, they are gaining an increasing interest as viable templates for ordered assembly of molecules and nanoparticles. However, liquid–liquid interfaces are more difficult to handle compared to solid–liquid interfaces; their intrinsic instability may affect the assembly process, especially in the case of multiple deposition. Indeed, some attempts have been made in the deposition of polymer multilayers at liquid–liquid interfaces, but with limited control over size and stability. This study reports on the preparation of an ultrastable liquid–liquid interface based on an O/W secondary miniemulsion and its possible use as a template for the self‐assembly of polymeric multilayer nanocapsules. Such polymer nanocapsules are made of entirely biodegradable materials, with highly controlled size—well under 200 nm—and multi‐compartment and multifunctional features enriching their field of application in drug delivery, as well as in other bionanotechnology fields.     

Active Encapsulation in Biocompatible Nanocapsules

Co‐precipitation is generally refers to the co‐precipitation of two solids and is widely used to prepare active‐loaded nanoparticles. Here, it is demonstrated that liquid and solid can precipitate simultaneously to produce hierarchical core–shell nanocapsules that encapsulate an oil core in a polymer shell. During the co‐precipitation process, the polymer preferentially deposits at the oil/water interface, wetting both the oil and water phases; the behavior is determined by the spreading coefficients and driven by the energy minimization. The technique is applicable to directly encapsulate various oil actives and avoid the use of toxic solvent or surfactant during the preparation process. The obtained core–shell nanocapsules harness the advantage of biocompatibility, precise control over the shell thickness, high loading capacity, high encapsulation efficiency, good dispersity in water, and improved stability against oxidation. The applications of the nanocapsules as delivery vehicles are demonstrated by the excellent performances of natural colorant and anti‐cancer drug‐loaded nanocapsules. The core–shell nanocapsules with a controlled hierarchical structure are, therefore, ideal carriers for practical applications in food, cosmetics, and drug delivery.     

Hot-melt extrusion – basic principles and pharmaceutical applications

Originally adapted from the plastics industry, the use of hot-melt extrusion has gained favor in drug delivery applications both in academia and the pharmaceutical industry. Several commercial products made by hot-melt extrusion have been approved by the FDA, demonstrating its commercial feasibility for pharmaceutical processing. A significant number of research articles have reported on advances made regarding the pharmaceutical applications of the hot-melt extrusion processing; however, only limited articles have been focused on general principles regarding formulation and process development. This review provides an in-depth analysis and discussion of the formulation and processing aspects of hot-melt extrusion. The impact of physicochemical properties of drug substances and excipients on formulation development using a hot-melt extrusion process is discussed from a material science point of view. Hot-melt extrusion process development, scale-up, and the interplay of formulation and process attributes are also discussed. Finally, recent applications of hot-melt extrusion to a variety of dosage forms and drug substances have also been addressed.     

Stability studies on colloidal suspensions of polyurethane nanocapsules

Generally nanocapsules suspensions are a colloidal system in a metastable state, there is aggregation due to attraction and repulsion forces between particles. The objective of this work was to bring the role of the polymeric membrane in the protection of the active drug against damaging caused by external agents and to select the monomer which leads to obtain stable formulation with the highest possible payload of the active drug. The stability testing involving visual aspect, particle size measurement, transmission electron microscopy (TEM) examination, and drug loss was conduced after 6 months of storage at different temperatures (4, 25, and 45 degrees C). The colloidal suspensions of nanocapsules were obtained using the combined interfacial polycondensation and spontaneous emulsification, the technique was used to encapsulate alpha-tocopherol using polyurethanes polymers. It is a one step procedure: An organic phase composed of a water miscible solvent (acetone), lipophilic monomer (Isophorone diisocyanate IPDI), oil, and a lipophilic surfactant, is injected in an aqueous phase containing hydrophilic monomer (diol with various molecular weight: 1,2-ethanediol (ED), 1,4-butanediol (BD), and 1,6-hexanediol (HD)) and hydrophilic emulsifying agent. The water miscible solvent diffuses to the aqueous phase, the oil precipitates as nano-droplets, and the two monomers react at the interface, forming a membrane around the nanoemulsion leading to nanocapsules. A good physical stability of suspensions corresponds to absence of symptoms such as sedimentation or agglomeration, significant size change and alpha-tocopherol degradation due to external agents such as oxygen, temperature, and ultraviolet (UV) irradiation. The size of nanocapsules before storage was about 232 +/- 3, 258 +/- 29, and 312 +/- 4 nm for ED, BD, and HD, respectively. After 6 months of storage, polyurethanes nanocapsules possess good stability against aggregation at 4 and 25 degrees C. Comparing results obtained using different monomers, it reveals that the polyurethane based on HD offers good protection of alpha-tocopherol against damaging caused by the temperature and UV irradiation.     

Freestanding Nanostructures via Layer‐by‐Layer Assembly

Freestanding flexible nanocomposite structures fabricated by layer‐by‐layer (LbL) assembly are promising candidates for many potential applications, such as in the fields of thermomechanical sensing, controlled release, optical detection, and drug delivery. In this article, we review recent advances in the fabrication and characterization of different types of freestanding LbL structures in air and at air/liquid and liquid/liquid interfaces, including micro‐ and nanocapsules, microcantilevers, freely suspended membranes, encapsulated nanoparticle arrays, and sealed‐cavity arrays. Several recently developed fabrication techniques, such as spin‐assisted coating, dipping, and micropatterning, make the assembly process more efficient and impart novel physical properties to the freestanding films.     

Effect of solvents quality on determination of particle size and polydispersity of nanoparticles

Nanotechnology is of great interest to researchers and industrialists and nanocolloidal carrier systems for drug delivery have been studied in great detail, but while much research has been carried out on the preparation of nanoparticles using a variety of techniques employing various solvents, no attention has been given to the quality of solvents used in the process of nanoparticles characterization. The present investigation aimed to study the effect of solvents quality on the chitosan nanoparticles characterization for average particle size (Z) and polydispersity index (P.I.). Particle size distribution study showed that the number of particles contributed by solvents significantly affects both the Z and P.I. of the nanoparticulate suspensions leading to ambiguous results. While the Z decreases upon dilution with organic solvents, the phosphate buffer and water causes a net increase in Z because of the introduction of larger extraneous nanoparticles. The P.I. was found to increase with dilution because of the differences in the size of the polymeric nanoparticles and the nanoparticles introduced by the solvent upon dilution. The study thus recommends use of the highest quality of solvents in nanoparticles manufacturing and characterization process to avoid the generation of erroneous results.     

Nanosponges – a completely new nano-horizon: pharmaceutical applications and recent advances

In recent years, nanosponges (NS) have gained tremendous impetus in drug delivery through nanotechnology. Nanosponges are capable of providing solutions for several formulation related problems. Through this review, scientists working in the field of nanotechnology can have an insight into the techniques of preparation, characterization and applications of NS. Owing to their small size and porous nature they can bind poorly-soluble drugs within their matrix and improve their bioavailability. They can be crafted for targeting drugs to specific sites, prevent drug and protein degradation and prolong drug release in a controlled manner. This review attempts to elaborate different schemes of synthesis of NS and their characterization. Factors affecting drug loading and release have been enumerated. Due to their advantages, NS have not only been explored for their pharmaceutical applications but also have large popularity in allied sciences, especially in water purification.     

A New Process for Drug Loaded Nanocapsules Preparation Using a Membrane Contactor

ABSTRACT

In this paper, we describe a new process for the preparation of drug loaded nanocapsules using a membrane contactor which may be scaled up for industrial applications. Nanocapsules are prepared according to the nanoprecipitation method. The organic phase (solvent, polymer, oil, and drug) is pressed through the pores of an ultrafiltration membrane via the filtrate side. The aqueous phase (water and surfactant) circulates inside the membrane module, and sweeps away the nanocaspules forming at the pore outlets. Two model drugs are selected for the preparation of drug loaded nanocapsules: indomethacin and vitamin E. It is shown that indomethacin loaded nanocapsules with a mean diameter of 240 nm and vitamin E loaded nanocapsules with a mean diameter of 230 nm are obtained with a 150,000 daltons ultrafiltration membrane, a transmembrane pressure of 3 bar, and a crossflow rate of 1.7 m.s^{? 1}. High fluxes are also obtained (around 0.6 m³/h.m²), leading to the preparation of 1.8 10^{? 3} m³ drug loaded nanocapsules in 8 min. The advantage of this membrane contactor compared to other processes for drug loaded nanocapsules preparation is shown to be its scale-up ability.     

Recent progress in nano-biotechnology: compartmentalized micro- and nanoparticles via electrohydrodynamic co-jetting

Compartmentalized particles enable co-presentation of dissimilar sets of properties, thereby offering a broad design space for multifunctional particles. Electrohydrodynamic co-jetting is a simple, yet versatile fabrication technique that can be used to prepare such multicompartmental particles and fibers. Processing conditions are summarized for co-jetting of aqueous and organic polymer solutions as well as nanoparticle suspensions. Because particles can comprise distinct polymers in different compartments, selective surface modification becomes possible. The latter can result in unidirectional interactions with cells or may pave new routes towards targeted drug delivery.     

Engineered microparticles based on drug–polymer coprecipitates for ocular-controlled delivery of Ciprofloxacin: influence of technological parameters

Abstract

Ciprofloxacin is a drug active against a broad spectrum of aerobic Gram-positive and Gram-negative bacteria, for the therapy of ocular infections. It requires frequent administrations owing to rapid ocular clearance and it is a good candidate for ocular controlled release formulations. The preparation of such drug release systems is still a challenge. Ionic interactions between ciprofloxacin and the polyelectrolytes chondroitin sulfate or lambda carrageenan result in coprecipitates that can act as microparticulate controlled release systems from which the drug is released after being displaced by the medium’s ions. In some formulations, Carbopol was added to improve the mucoadhesive properties. The aim of this research was the study of the influence of the technological parameters of the preparation method of coprecipitates on their particle size, with the goal of achieving particles engineered with a size suitable for the ocular administration. Technological parameters taken into account were: concentration of drug and polymer solutions utilized for the preparation of interaction products, possible use of surfactants (kind and concentration), temperature of the solutions and stirring during the process of preparation of the coprecipitates. Preliminary stability study tests were carried out to further characterize the leader formulation. Particle size in suspensions for ocular drug delivery is a critical parameter influencing the quality of the formulation. The results obtained from this study show that chondroitin sulfate coprecipitates present the best characteristics in terms of particle size suitable for ocular administration. A further improvement of the particle size characteristics has been obtained with the addition of surfactants.     

Synthesis and characterisation of PEG modified chitosan nanocapsules loaded with thymoquinone

Thymoquinone (TQ), a major bioactive compound of Nigella sativa seeds has several therapeutic properties. The main drawback in bringing TQ to therapeutic application is that it has poor stability and bioavailability. Hence a suitable carrier is essential for TQ delivery. Recent studies indicate biodegradable polymers are potentially good carriers of bioactive compounds. In this study, polyethylene glycol (PEG) modified chitosan (Cs) nanocapsules were developed as a carrier for TQ. Aqueous soluble low molecular weight Cs and PEG was selected among different biodegradable polymers based on their biocompatibility and efficacy as a carrier. Optimisation of synthesis of nanocapsules was done based on particle size, PDI, encapsulation efficiency and process yield. A positive zeta potential value of +48 mV, indicating good stability was observed. Scanning electron microscope and atomic‐force microscopy analysis revealed spherical shaped and smooth surfaced nanocapsules with size between 100 to 300 nm. The molecular dispersion of the TQ in Cs PEG nanocapsules was studied using X‐ray powder diffraction. The Fourier transform infrared spectrum of optimised nanocapsule exhibited functional groups of both polymer and drug, confirming the presence of Cs, PEG and TQ. In vitro drug release studies showed that PEG modified Cs nanocapsules loaded with TQ had a slow and sustained release.Inspec keywords: nanomedicine, drug delivery systems, polymers, scanning electron microscopy, electrokinetic effects, atomic force microscopy, X‐ray diffraction, Fourier transform infrared spectraOther keywords: PEG modified chitosan nanocapsules, thymoquinone, bioactive compound, Nigella sativa seeds, bioavailability, polyethylene glycol, molecular weight, zeta potential, scanning electron microscope, atomic force microscopy, molecular dispersion, X‐ray powder diffraction, Fourier transform infrared spectrum     

Strategic use of affinity-based mass spectrometry techniques in the drug discovery process.

Advances in biomolecular mass spectrometry (Bio-MS) have made this technique an invaluable tool for analytical chemists and biochemists alike. The applicability of Bio-MS approaches in drug discovery now encompasses in vitro, cellular, and in vivo pharmacological and clinical applications in an unprecedented expansion of utility. As a result, the role of Bio-MS in pharmaceutical discovery continues to proliferate for both structural and functional characterization of biomolecules. From target characterization to lead optimization, affinity techniques have been used to purify, probe, and enrich analytes of interest. Affinity selection employed prior to MS analysis can "edit" out extraneous noise and enable the researcher to examine only what is important. These affinity-based methods can be used as an alternative strategy when classical biochemical techniques are insufficient in advancing difficult projects. We have applied various affinity techniques in conjunction with mass spectrometry throughout the drug discovery process. This perspective will describe affinity-based mass spectrometry methodologies and related concepts, illustrated with original results.     

Sugar coated ceramic nanocarriers for the oral delivery of hydrophobic drugs: formulation, optimization and evaluation

In order to enhance the delivery of poorly-soluble drugs, we have explored aquasomes (three-layered, ceramic core based, oligosaccharide coated nanoparticles) as potential carriers for the delivery of model hydrophobic drug piroxicam (log P = 3.1). Ceramic nanoparticles were prepared using two techniques; namely, co-precipitation by refluxing and co-precipitation by sonication. Core preparation was finally done using sonication approach; based on the higher % yield (42.4 ± 0.4%) and shorter duration (1 day) compared to the reflux method (27.4 ± 2.05%, 6 days). Lactose loading onto ceramic core was achieved using adsorption. Colorimetric analysis of lactose coating was done using Anthrone method. Optimization of process variables namely, incubation time and core to coat ratio (for sugar loading) was carried out. Optimum time of incubation was 3 h and the core to coat ratio was 4:1. The drug loading was achieved by incubating the sugar loaded cores in different concentrations of piroxicam solution and it was found that 1.5% w/v piroxicam was optimal. Structural characterization using Fourier-Transform Infra Red Spectroscopy (FTIR) confirmed the presence of sugar coating onto the core. Morphological evaluation using transmission electron microscopy (TEM) revealed spherical nanoparticles (size 56.56 ± 5.93 nm for lactose coated core and 184.75 ± 13.78 nm for piroxicam loaded aquasomes) confirming the nanometric dimensions.