Nylon Microcapsules. II. Effect of Selected Variables on Theophylline Release

The effect of selected variables on the release characteristics of theophylline microcapsules prepared with 1,6-hexamethylene diamine and sebacoyl chloride via interfacial polycondensation has been investigated. The nature of the microcapsules and the release characteristics of theophylline from the microcapsules were affected by the type of organic phase, particle size, stirring speed, and rate of addition of sebacoyl chloride during the preparation of microcapsules. The aggregation of the final product was generally less at the lower speeds of stirring. Decreasing the rate of additon of sebacoyl chloride increased the aggregation of the final product as well as the release of theophylline. Decreasing the particle size of the microcapsules increased the release of theophylline from the microcapsules.     

Controlling the internal morphology of aqueous core-PLGA shell microcapsules: promoting the internal phase separation via alcohol addition

The ability to control the internal core architecture of polymeric microcapsules has a direct impact on their applications. However, this task, especially to produce microcapsules with a high percentage of mononuclear aqueous cores, proved to be challenging. In this work, and in continuation to our previous studies, we report a facile protocol to prepare poly(D,L-lactide-co-glycolide) (PLGA) microcapsules with unprecedented percentage (almost 100%) of mononuclear aqueous cores by the internal phase separation method via adding alcohols. Different types of alcohols (methanol, ethanol, propanol, isopropanol, butanol, and octanol) were incorporated into the internal phase solution and then emulsified into mineral oil. In situ monitoring of emulsion droplets was performed by phase contrast microscopy at different time points and the percentage of mononuclear droplets was measured. While alcohol-free formulation ended up with only around 51% of mononuclear microcapsules, incorporating alcohols resulted in the formation of more than 90% of mononuclear microcapsules. Octanol, in particular, exhibited an outstanding performance as its incorporation led to an immediate (at 0?h) formation of almost entirely mononuclear microcapsules. Final microcapsules exhibited spherical shape with mean particle size in the range of 1–2?µm as depicted by scanning electron microscopy and dynamic light scattering analysis.     

Oil encapsulation techniques using alginate as encapsulating agent: applications and drawbacks

Oils are used in agriculture, nutrition, food and cosmetics; however, these substances are oxidisable and may readily lose their properties. To reduce their degradation or to mask certain undesirable aspects, one strategy consists in encapsulating the oil in inert structures (capsules). The capsules are classified according to the morphology, the number of cores and size, can be produced by several techniques: jet-cutting, vibrating jet, spray-drying, dispersion and milli-microfluidic. Among the polymers used as a membrane in the capsules, alginates are used in oil encapsulation because of their high gelling capacity, biocompatibility and low toxicity. In the presence of calcium ions, the alginate macromolecules crosslink to form a three-dimensional network called hydrogel. The oil encapsulation using alginate as encapsulating material can be carried out using technologies based on the external, internal or inverse gelation mechanisms. These capsules can found applications in areas as cosmetics, textile, foods and veterinary, for example.     

A Novel Method for Determination of Sterility of Microcapsules and Measurement of Viability of Encapsulated Organisms

A method of determining the viability of microencapsulated microorganisms (Bacillus Calmette Guerin) is reported. This method was also used to measure the effectiveness of aseptic production of mi-crocapsules in maintaining the interior of the microcapsules free from contamination by microorganisms. This method is advantageous over conventional plating methodology, as plating can only determine external contamination of microcapsules and similar devices. It involves the detection of ¹⁴CO₂, which is generated by the metabolism of ¹⁴C-labeled fatty acid in the growth medium by encapsulated microorganisms. The method depends on the semiper-meable nature of the microcapsule walls, which allows passage of ¹⁴C-palmitic acid and ¹⁴CO₂. BCG organisms encapsulated within an alginate-polylysine-alginate microcapsule (5–15 µm) (1) were shown to be viable, and no contaminating organism(s) was present. Methods suitable for the aseptic production and freeze drying of alginate–polylysine–alginate BCG microcapsules, which retain the viability of the organisms, are reported.     

Characterization of a Hot-Melt Fluid Bed Coating Process for Fine Granules

The equipment modifications and process changes necessary to perform hot-melt particle coating in a fluid bed granulator are reviewed. A specific case is presented in which partially hydrogenated cottonseed oil is coated onto fine granules (mean particle size, 77 µm; range, 10–150 µm; one standard deviation is 10 µm) composed of a hydrophobic drug and sucrose. The major variables were product bed temperature, temperature of the wax, spray rate, and atomization air pressure. The product bed temperature was selected to give the optimum congealing rate, and the latter three variables were varied in a statistically designed experiment. The physical properties of wax-coated granules fabricated using combinations of process variables were examined. Response surface analysis was used to determine the optimum process settings in terms of dissolution, particle size, and density of the coated product. This system proved quite adequate for the production of uniformly coated granules, with the best product being obtained at the optimized conditions using 120°C atomization air and molten coating temperature, 30 g/min as the spray rate, and an atomization air pressure of 5 bar.     

Slow release polymer-drug systems obtained by moisture promoted polyreactions. 1. Codeine resinate encapsulated in poly(alkyl α-cyanoacrylates)

Abstract

Samples of codeine resinate consisting of a carboxylic cation exchanger (as a polymeric carrier) and codeine (as a drug) were coated with poly(alkyl α-cyanoacrylates) by suspending and stirring wet resinate beads in a toluene solution of the monomer. Methyl, ethyl and n-butyl α-cyanoacrylates were used as monomers. Each coated material released codeine more slowly than the non-coated. The data obtained confirmed that water promoted the polymerization of alkyl α-cyanoacrylates, which proceeded at the surface of the wet resinate beads. The rate of codeine release depended on the type of monomer used for coating, the monomer/resinate feed ratio and the plymerization time.     

Enhanced stability of vitamin A palmitate microencapsulated by γ-cyclodextrin metal-organic frameworks

γ-Cyclodextrin metal-organic frameworks (γ-CD-MOFs) are highly porous and bio-friendly novel materials formed by γ-CD as an organic ligand and potassium ion as an inorganic metal centre. The aim of this study was to enhance the stability of vitamin A palmitate (VAP) using γ-CD-MOFs as the carrier. Herein, γ-CD-MOFs displayed VAP microencapsulating capacity of 9.77?±?0.24% with molar ratio as n_MOFs:n_VAP?=?3.2:1.0. It was important to find that the improved stability of VAP microencapsulated by γ-CD-MOFs without addition of any antioxidant(s) was better than that of the best available reference product in the market, with 1.6-fold elongated half-life. The protecting mechanism of γ-CD-MOFs for VAP contributed that VAP molecules preferentially curled inside the cavities of dual γ-CD pairs in γ-CD-MOFs. It was proved that γ-CD-MOFs were an efficient new carrier to deliver and protect VAP for food and pharmaceutical applications.     

Microencapsulation of higher hydrocarbon phase change materials by in situ polymerization

Three higher hydrocarbon phase change materials (PCMs) with melting points of 25, 40 and 50°C were microencapsulated by in situ polymerization of amino-aldehyde resins. Trimethylolmelamine (TMM) and hexamethoxymethylolmelamine (HMMM) were studied as amino-aldehyde pre-polymers for microcapsule wall formation, in combination with emulsifying/modifying agents based on styrene-malein anhydride copolymers (SMA) of different molecular weights and different styrene-maleic acid anhydride ratios. Microcapsule sizes, size distribution and wall permeability were analysed. A mathematical model was developed for comparing the mechanical resistance of different batches of microcapsules, produced at different TMM-SMA ratios. Larger microcapsules with thicker walls and larger pores (M_LAR) expressed lower resistance to breakage than slightly smaller microcapsules with thinner walls and finer pore structure (M_SMA). Mathematical data were confirmed by a smudging colouration test. Laboratory microencapsulation process parameters were optimized to obtain impermeable microcapsules with improved mechanical stability. The process was transferred into a 10?l pilot reactor for two PCMs with melting points of 25 and 40°C. Dry powder of microencapsulated PCMs was obtained by spray drying of aqueous microcapsule suspensions.     

THE THERMAL POLYMERIZATION OF AMINO ACIDS: The Role and Fate of the Reactants

Amino acid containing polymers were synthesized by heating mixtures of aspartic acid, glutamic acid, glycine, alanine, valine, leucine, isoleucine, and proline in the absence of water at temperatures of 180° to 190°C for several hours. The resulting product was fractionated by dialysis, gel filtration, and chromatography and electrophoresis on paper. The larger polymers were found to be rich in aspartic acid and poor in proline, while the smaller molecules were rich in glutamic acid and contained proline as a significant constituent. The N-terminal positions are believed to be occupied largely by pyroglutamic acid, while the C-terminal positions are comprised exclusively of aliphatic amino acids. Aspartic acid and glutamic acid were individually treated to the polymerization conditions. Little reaction of aspartic acid was observed, but glutamic acid formed a melt and upon cooling a glass. Investigation of this product indicated it to be a highly hydrogen bonded system of pyroglutamic and glutamic acids. The model system of glutamic acid and decylamine produced under polymerization conditions, the decylamide of pyroglutamic acid. The accumulated results suggest a model for thermal polymerization.     

Physical and Biochemical Characterization of Chemically Treated Pollen Shells for Potential Use in Oral Delivery of Therapeutics

Allergen-free pollen shells obtained from natural pollen grains have recently attracted attention as microcapsules for oral therapeutic delivery. We have recently developed a chemical treatment method that enables successful retrieval of hollow pollen shells from diverse species. A comprehensive characterization is critical to characterize the effects of chemical treatment which will not only benchmark the pollen treatment process but can also lay the foundation of quality control procedures to check allergen-removal efficiency during pollen treatment. Therefore, in this study, we followed the effects of chemical treatment on 4 different pollen species using electron microscopy, elemental analysis, gel electrophoresis, confocal microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. These analyses revealed that acetone treatment removed lipids from the pollen surface. Phosphoric acid treatment removed proteins and nucleic acids from the pollen core and transformed esters into carboxylic acids. Potassium hydroxide hydrolysis changed carbohydrate composition of the pollen wall. Chemically treated pollen shells exhibited hydroxyl and carboxyl functional groups on their surface. Overall, we propose that confocal microscopy could be used as a rapid scanning technique to visualize the removal of biomolecules, whereas Fourier-transform infrared combined with gel electrophoresis could be used as a more objective approach for analysis and benchmarking.     

Synthesis and release studies of shikonin-containing microcapsules prepared by the solvent evaporation method

Microcapsules, containing the pharmaceutical substance shikonin, were prepared by the solvent evaporation method in order to enhance shikonin stability (reduce photo-oxidation, polymerization), decrease its hydrophobicity and control its release rate. The effect of various parameters, such as type of polymer, type and concentration of surfactant, solvent volume and mastic gum (Pistacia lentiscus resin) content/concentration as core additive, on the characteristics of the produced microcapsules and the release rate of shikonin, were experimentally investigated. Among the polymers tested for matrix, ethylcellulose (EC) of viscosity 10 cp was the most successful; EC 100 cp and mastic gum result in larger/compact particles with no pores and much slower release. Sodium dodecyl sulphate (SDS) results in microcapsules with desirable morphological and physicochemical characteristics, while polyethylene glycol (PEG) and polyvinyl alcohol (PVA) are not indicated as surfactants in shikonin microencapsulation. Decreasing the solvent volume (dichloromethane) results in increased mean particle size and, thus, in slower release rate of shikonin, while the incorporation of mastic gum in the capsule core results in better control of shikonin release. Finally, the combination of EC 10 cp as matrix, mastic gum as core additive, low dichloromethane (DCM) volume and low SDS concentration results in microcapsules with the best characteristics in terms of efficiency, loading, release and particle size distribution.     

Microagglomeration of pulverized pharmaceutical powders using the Wurster process I.: Preparation of highly drug-incorporated, subsieve-sized core particles for subsequent microencapsulation by film-coating

A novel agglomeration process of pulverized pharmaceutical powders into subsieve-sized agglomerates (microagglomeration) was designed for manufacturing highly drug-incorporated core particles for subsequent microencapsulation by film-coating. The microagglomeration of pulverized phenacetin powder, whose mass median diameter was 9 μm, was performed by spraying an aqueous colloidal dispersion of acrylic polymer, Eudragit® RS30D, as a binding/coating agent using a spouted bed assisted with a draft tube (the Wurster process), and the effect of process variables was examined. An appropriate spray liquid flow rate made it possible to produce microagglomerates of 20–50 μm with 60% yield. However, 10% of the product still survived as particles smaller than 10 μm even at the elevated liquid flow rate. In contrast, the survived particles smaller than 10 μm tended to be predominantly reduced to 2%, while coarse agglomerates larger than 53 μm were not excessively produced, by additionally setting a fixed bed of glass beads in the spouted bed apparatus. The length of the draft tube influenced compaction of the agglomerates as well as their surface-smoothening. Equipping the fixed bed of the glass beads and the long draft tube in the spouted bed allowed us to prepare microagglomerates of 20–50 μm at yield of 55% applicable as highly drug-incorporated, free-flowing, surface-smoothed, narrowly size-distributed core particles for subsequent microencapsulation by film-coating.     

Encapsulation of a pressure-sensitive adhesive by spray-drying: microparticles preparation and evaluation of their crushing strength

An industrial pressure-sensitive adhesive was microencapsulated by spray-drying using an aqueous colloidal ethylcellulose dispersion (Aquacoat® ECD) plasticised by triacetin to form the wall material. Unloaded (0:100) and adhesive-loaded (25:75) particles were produced in a Büchi B-191 mini spray-dryer with product yields of 62% and 57%, respectively. Microparticles were spherical and narrow sized with mean D_3,2 diameters of 3.165?±?0.001 and 5.544?±?0.105?µm, respectively. The microparticles were found to redisperse well in water and exhibit enough stability in neutral and alkaline aqueous media to be further used in a coating slip. Crush tests on single microparticles with diameters ranging from 2 to 12?µm were performed using a nanoindenter. They revealed that the crushing force of both kinds of microparticles increased linearly with their diameter and that the adhesive loading reduced the mechanical strength of the prepared microparticles.     

Modification of bovine serum albumin structure following reaction with 4,5(E)-epoxy-2(E)-heptenal

Bovine serum albumin (BSA) was incubated for different periods of time and in the presence of several concentrations of 4, 5(E)-epoxy-2(E)-heptenal, at pH 7.4 and 37 degrees C, in an effort to analyze the changes produced in its structure as a consequence of its reaction with this product of lipid oxidation. The epoxyalkenal modified the primary structure of BSA as determined by lysine losses and formation of oxidative stress product epsilon-N-pyrrolylnorleucine (Pnl), which depended on the concentration of the aldehyde and the incubation time. These changes also modified secondary and tertiary structures of the protein, which were determined by studying protein denaturation and polymerization. In addition, all these modifications were parallel to the development of color and fluorescence, which were produced as a consequence of the formation and polymerization of pyrrole amino acid residues. The above results indicated that epoxyalkenals modify the protein structure and develop color and fluorescence. A failure in the degradation of these modified proteins might induce their accumulation and, thus, participation in lipofuscin or age pigments formation.     

Application of acid-catalyzed hydrolysis of dispersed organic solvent in developing new microencapsulation process technology

The aim of this study was to evaluate a new microencapsulation technology employing an acid-catalyzed solvent extraction method in conjunction to an emulsion-based microencapsulation process. Its process consisted of emulsifying a dispersed phase of poly(D,L-lactide-co-glycolide) and isopropyl formate in an aqueous phase. This step was followed by adding hydrochloric acid to the resulting oil-in-water emulsion, in order to initiate the hydrolysis of isopropyl formate dissolved in the aqueous phase. Its hydrolysis caused the liberation of water-soluble species, that is, isopropanol and formic acid. This event triggered continual solvent leaching out of emulsion droplets, thereby initiating microsphere solidification. This new processing worked well for encapsulation of progesterone and ketoprofen that were chosen as a nonionizable model drug and a weakly acidic one, respectively. Furthermore, the structural integrity of poly(D,L-lactide-co-glycolide) was retained during microencapsulation. The new microencapsulation technology, being conceptually different from previous approaches, might be useful in preparing various polymeric particles.     

The effect of polymer molecular weight and cell seeding density on viability of cells entrapped within PEGDA hydrogel microspheres

Abstract

Cell microencapsulation can be used in tissue engineering as a scaffold or physical barrier that provides immunoisolation for donor cells. When used as a barrier, microencapsulation shields donor cells from the host immune system when implanted for cell therapies. Maximizing therapeutic product delivery per volume of microencapsulated cells necessitates first optimising the viability of entrapped cells. Although cell microencapsulation within alginate is well described, best practices for cell microencapsulation within polyethylene glycol is still being elucidated. In this study we microencapsulate mouse preosteoblast cells within polyethylene glycol diacrylate (PEGDA) hydrogel microspheres of varying molecular weight or seeding densities to assess cell viability in relation to cell density and polymer molecular weight. Diffusion studies revealed molecule size permissible by each molecular weight PEGDA towards correlating viability with polymer mesh size. Results demonstrated higher cell viability in higher molecular weight PEGDA microspheres and when cells were seeded at higher cell densities.     

Preparation of controlled release anticancer agents I: 5-fluorouracil-ethyl cellulose microspheres

Abstract

Microspheres of 5-fluorouracil have been prepared, using three grades of ethyl cellulose as wall forming materials, and utilizing a solvent evaporation technique under ambient conditions. An alcoholic solution of 5-fluorouracil and polymer was dispersed in liquid paraffin containing 33.3 per cent n-heptane. The effect of stirring rate, time of stirring, drug loading, and polymer grade on drug release in two different media were evaluated. The drug loaded particles were spherical in shape and had a diameter range of 25-200 mm and were suitable for incorporating into a gel base. Drug release studies in aqueous media, showed that acidic media provide a faster release rate than neutral media. The drug release study from an aqueous gel base preparation at pH 7.0 through a synthetic membrane was found to be promising for formulation of a gel-microsphere product for the treatment of skin lesions.     

Microencapsulation of Clostridium acetobutylicum ATCC 824 spores in gellan gum microspheres for the production of biobutanol

Abstract

The purpose of the present study was to provide further insights on the applicability of microencapsulation using emulsification method, to immobilise Clostridium acetobutylicum ATCC 824 spores, for biobutanol production. The encapsulated spores were revived using heat shock treatment and the fermentation efficiency of the resultant encapsulated cells was compared with that of the free (non-encapsulated) cells. The microspheres were easily recovered from the fermentation medium by filtration and reused up to five cycles of fermentation. In contrast, the free (non-encapsulated) cells could be reused for two cycles only. The microspheres remained intact throughout repeated use. Although significant cell leakage was observed during the course of fermentation, the microspheres could be reused with relatively high butanol yield, demonstrating their role as microbial cell nurseries. Both encapsulated and liberated cells contributed to butanol production.     

Effect of prolonged gelling time on the intrinsic properties of barium alginate microcapsules and its biocompatibility

Pericapsular fibrotic overgrowth (PFO) may be attributed to an immune response against microcapsules themselves or to antigen shedding through microcapsule pores from encapsulated islet tissue. Modification of microcapsules aimed at reducing pore size should prevent PFO and improve graft survival. This study investigated the effect of increased gelling time (20 vs. 2?min) in barium chloride on intrinsic properties of alginate microcapsules and tested their biocompatibility in vivo. Prolonged gelling time affected neither permeability nor size of the microcapsules. However, prolonged gelling time for 20?min produced brittle microcapsules compared to 2?min during compression test. Encapsulation of human islets in both types of microcapsules affected neither islet viability nor function. The presence of PFO when transplanted into a large animal model such as baboon and its absence in small animal models such as rodents suggest that the host immune response towards alginate microcapsules is species rather than alginate specific.     

肺鞍向汉防己甲素缓释微囊的小鼠体内分布

目的：测定汉防己甲素在体内样品中的浓度,研究汉防己甲素经微囊化后的体内分布特点。方法：建立样品中江防己甲素浓度测定的RP-HPLC法,对比汉防己甲素水针剂和微囊混悬液经小鼠尾静脉注射后,不同时间时汉防己甲素的浓度值,分析药物的肺靶向性。结果：生物样品检验方法简便易行,结果准确,微囊化汉防己甲素在肺中的浓度明显提高,且缓慢降低,具有明显的肺靶向性。结论：汉防己甲素经微囊化后,可浓集于肺部,且具有缓慢释放的特点,对肺动脉高压的防治具有重要意义。