Showing papers in "Journal of Microencapsulation in 1984"
TL;DR: A novel technique was developed which made possible high-yield entrapment of Factor VIII in much more stable liposomes based on the saturated phospholipid, distearoyl phosphatidylcholine, which has a number of other important features which make it an attractive method for the incorporation of a wide range of materials into liposome.
Abstract: Different types of liposomes composed of a variety of lipids have been compared for their ability to incorporate Factor VIII, with a view to attempting oral therapy of haemophilia. Reverse evaporation liposomes (REV) composed of unsaturated phospholipids, allowed adequate levels of entrapment for administration to haemophilic dogs, but failed to promote entry of Factor VIII into the vasculature, possibly due to liposome breakdown and denaturation of Factor VIII within the gastrointestinal tract. A novel technique was therefore developed which made possible high-yield entrapment of Factor VIII in much more stable liposomes based on the saturated phospholipid, distearoyl phosphatidylcholine. This new technique has a number of other important features which make it an attractive method for the incorporation of a wide range of materials into liposomes.
63 citations
TL;DR: The haemoglobin-trapping efficiency of the cells was found strongly dependent on the pH of the carboxymethylchitin solution used and the degree of cell disintegration was in the increasing order, anionic greater than cationic greater than nonionic.
Abstract: Liposome-type artificial red blood cells stabilized with carboxymethylchitin (mean diameter 310 nm) were prepared by a two-step emulsification technique. Sheep haemolysate was dispersed as fine droplets in a lecithin solution in dichloromethane to yield a W/O-type emulsion. The W/O emulsion thus obtained was then dispersed in an aqueous carboxymethylchitin solution to give a W/O/W-type complex emulsion. Removal of the organic solvent by evaporation from the complex emulsion left an aqueous suspension of the artificial red blood cells. The haemoglobin-trapping efficiency of the cells was found strongly dependent on the pH of the carboxymethylchitin solution used.The artificial red blood cells underwent disintegration by the action of surfactants. When a comparison was made among those surfactants which have the same alkyl chain length, the degree of cell disintegration was in the increasing order, anionic cationic nonionic. Globulin and fibrinogen produced no disintegration of the cells while album...
40 citations
TL;DR: Preliminary in vivo results on rabbit eyes suggested that the liposomal vehicle was probably unable to improve sufficiently the corneal penetration of pilocarpine to reach satisfactory therapeutic levels when administered at lower concentrations than commonly used.
Abstract: Liposomes containing either pilocarpine hydrochloride or pilocarpine free base were prepared by the sonication method. This manufacturing process yielded after removal of non-encapsulated solute, small multilamellar vesicles (MLV) as was confirmed by electron microscopy examinations. For an identical liposomal composition, the encapsulation capacity and the drug content of the liposomes were drastically higher for pilocarpine hydrochloride than for pilocarpine free base. Investigation of the preparative parameters revealed that increasing the initial amount of drug decreased the drug content and the encapsulation efficiency of the liposomes formed. Since fixed amounts of lipids were used, the volume sequestration rate decrease was attributed to a moderate viscosity increase of the dispersion medium. Increase of phospholipid concentration at a constant ratio of cholesterol and dicetylphosphate to phosphatidylcholine reduced the aqueous volume entrapped per mg of lipid and subsequently the pilocarpi...
33 citations
TL;DR: This technique appears to be the most successful and convenient procedure for the long-term storage of liposomes for CT contrast agents.
Abstract: To facilitate acceptance and use of radiopaque liposomes as novel CT contrast agents, we developed a technique that permits their long-term storage at room temperature. This study compares standard storage procedures with the new method. Multilamellar vesicles were prepared with egg lecithin, cholesterol and stearylamine (4:1:1 molar ratio) as well as diatrizoate. After synthesis, the vesicles were separated into batches: one portion was kept frozen (FRO), another was lyophilized and stored at room temperature (LYO-RT), and a third was thawed and stored at room temperature (RT). Size, structure and biodistribution of vesicles in all three groups were assessed over a 6-month period. Freeze-drying the vesicles caused no apparent damage to their membranes The RT group showed marked aggregation after 1 month, while the LYO-RT and FRO vesicles showed only a slight shift to larger particles after 6 months. At this time, there was no significant change in the biodistribution of the LYO-RT vesicles compar...
28 citations
TL;DR: The degradation of polybutylcyanoacrylate and PHC nanoparticles, together with their association with and toxicity towards isolated hepatocytes, were determined and Nanoparticles were not taken up by rat hepatocytes at a significant level.
Abstract: The degradation of polybutylcyanoacrylate (PBC) and polyhexylcyanoacrylate (PHC) nanoparticles, together with their association with and toxicity towards isolated hepatocytes, were determined. Nanoparticles were not taken up by rat hepatocytes at a significant level. The LD50s of PBC and PHC nanoparticles towards hepatocytes were 0.4mg/2 × 106 cells and >1 mg/2 × 106 cells respectively. This hepatocyte toxicity cannot be attributed solely to the formaldehyde formed during degradation.
25 citations
TL;DR: The use of sustained-release preparations of theophylline has become routine in the treatment of bronchial asthma and microencapsulation provides a possible means of producing such a product, according to the present paper.
Abstract: The use of sustained-release preparations of theophylline has become routine in the treatment of bronchial asthma. Microencapsulation provides a possible means of producing such a product. The present paper examines, by means of triangular diagrams, the phases present in the system ethylcellulose-petroleum ether-toluene. The separated cellulose was used to coat the drug theophylline. The effects of temperature, petroleum ether fraction, solvent:non-solvent ratio and rate of non-solvent addition on the size and size distribution of the microcapsules was studied.
24 citations
TL;DR: Poly(lactic acid) microcapsules of oxytetracycline hydrochloride were prepared by precipitation of the polymer from a solution when a non-solvent was added to a polymer solution in which the drug had been dispersed.
Abstract: Poly(lactic acid) microcapsules of oxytetracycline hydrochloride were prepared by precipitation of the polymer from a solution when a non-solvent was added to a polymer solution in which the drug had been dispersed. Three types of microcapsules were prepared by varying the amount of drug encapsulated, as well as by using two samples of polymer with different molecular weights. The product obtained was of a matrix character consisting of agglomerated capsules. The drug release in vitro, for the best batch, was completed within 12 hours. Serum levels of the drug in rabbits treated by intramuscular injection were prolonged maximally up to 24 hours depending upon the type of microcapsules.
20 citations
TL;DR: Two methods of microencapsulation of amoxicillin, an orally administered antibiotic, were studied and a nomogram was made using pharmacokinetic parameters obtained after administration of a conventional formulation to establish a suitable design and for the evaluation of the sustained release microcapsules.
Abstract: Two methods of microencapsulation of amoxicillin, an orally administered antibiotic, were studied. One is based on dispersion of gelatin-amoxicillin mixture in liquid paraffin followed by drying and hardening with formalin-isopropanol treatment; the other is based on dispersion of ethylcellulose—amoxicillin mixture in purified water containing sodium lauryl benzene sulphonate. The microcapsules were recovered as discrete, free-flowing fine granules with a particle diameter of about 250–1000 μm. Dissolution of amoxicillin from ethylcellulose microcapsules was suppressed considerably with a zero-order dissolution pattern in solutions of various pH. Gastric-emptying-controlled rabbits were used for the in vivo evaluation of gelatin and ethylcellulose microcapsules. The ethylcellulose microcapsule containing 25 per cent amoxicillin showed a significantly sustained release pattern of amoxicillin. To establish a suitable design and for the evaluation of the sustained release microcapsules, a nomogram wa...
19 citations
TL;DR: Results indicate that microencapsulation can prolong persistent effects by 2–12 times, enhance safety and subdue offensive odour, and the production cost is comparatively low.
Abstract: Since 1978 we have prepared microencapsulated insecticides by complex coacervation and interfacial polymerization for household insect pest control, fenthion being the main core element. A series of tests have been conducted against mosquitoes (Culex pipiens quinquefasciatus), cockroaches (Periplaneta americana) and bedbugs (Cimex lectularius), and the results indicate that microencapsulation can prolong persistent effects by 2-12 times, enhance safety and subdue offensive odour. Furthermore, the production cost is comparatively low.
17 citations
TL;DR: A new method was proposed to prepare monocored water-loaded microcapsules with diameters of 50 microns or larger by making use of the process of interfacial polymer deposition, which resulted in a patchwork-like structure in which polystyrene-rich islands are dispersed in the ethylcellulose-rich sea.
Abstract: A new method was proposed to prepare monocored water-loaded microcapsules with diameters of 50 μm or larger by making use of the process of interfacial polymer deposition. A solution of ethylcellulose or polystyrene in dichlorometh ane was added dropwise to an O/W emulsion in which n-hexane was dispersed as fine droplets in aqueous gelatin solution. Successive evaporation of dichloro-methane at 40d`C and n-hexane at 80d`C gave monocored water-loaded ethyl cellulose or polystyrene microcapsules. Monocored water-loaded ethylcellu lose/polystyrene composite microcapsules were similarly prepared using mixed solutions of the two polymers in dichloromethane instead of ethylcellulose or polystyrene solution. When those mixed solutions which exhibit phase separation were used, the composite microcapsules obtained had a patchwork-like structure in which polystyrene-rich islands are dispersed in the ethylcellulose-rich sea.
17 citations
TL;DR: The interfacial polymerization process used in the present study produced individual cross-linked albumin microcapsules, the particle size of which depended on the emulsification stirring rate, and the variation in cross-linking agent concentration altered the microcapsule wall properties.
Abstract: The interfacial polymerization process used in the present study produced individual cross-linked albumin microcapsules, the particle size of which depended on the emulsification stirring rate. The variation in cross-linking agent concentration altered the microcapsule wall properties. As shown by SEM observations, microcapsules prepared with low acyl chloride concentrations presented rippled surfaces, while the surfaces of the microcapsules prepared with high acyl chloride concentrations were smooth. It was then suggested that the membranes of the weakly cross-linked microcapsules consisted of cross-linked and denatured albumin. Embolization experiments in the dog kidney showed that the weakly cross-linked microcapsules were biodegradable within 7 days, whereas the highly cross-linked microcapsules were degraded over more than 14 days and led to prolonged ischaemia. The results of the histological experiments carried out on a further eight dogs supported the previous findings yielded by the angio...
TL;DR: The authors discuss the advantages and the possibilities of this method in relation to selective catheterization and to the various time periods required for microparticle biodegradation and the kinetics of drug release.
Abstract: Chemoembolization is the injection of active-principle-bearing microparticles via selective catheterization. The authors discuss the advantages and the possibilities of this method in relation to selective catheterization and to the various time periods required for microparticle biodegradation and the kinetics of drug release. Particular attention is paid to intra-arterial chemoperfusion, chemoembolization and chemoinfusion with microparticles.
TL;DR: The Coulter counter has become one of the methods of choice for the measurement of small particle sizes, but many colloidal walled microcapsules are prone to hydration when dispersed in the electrolyte solution used in Coulter measurements, producing different size analyses dependent upon the time of measurement.
Abstract: The Coulter counter has become one of the methods of choice for the measurement of small particle sizes However, many colloidal walled micro capsules are prone to hydration when dispersed in the electrolyte solution used in Coulter measurements This hydration causes the walls to swell, producing different size analyses dependent upon the time of measurement In the present work the change in size with time was studied for microcapsules with gelatin acacia coacervate, or ethylcellulose, walls The former, although rendered insoluble with formalin, still hydrated; the latter were almost unaffected by water A sample size of 30 mg was required to prevent blocking of the orifice with larger samples, or too few particles to permit measurement in smaller samples The coacervate coated microcapsules showed a bimodal distribution, in part due to aggregation of smaller microcapsules, and this distribution changed significantly over the time of measurement Although the peak due to larger microcapsules di
TL;DR: Egg albumin microspheres containing sulphamethizole have been prepared by a capillary extrusion procedure and showed a burst effect for drug release in acidic dissolution media and the release tended to tail off as the matrix became depleted of drug.
Abstract: Egg albumin microspheres containing sulphamethizole have been prepared by a capillary extrusion procedure. The microspheres were coarse (dvn = 1835 μm) with a narrow size distribution and tended to lose their spherical shape on drying. Scanning electron microscopy revealed that the microspheres were porous with drug concentrated at the periphery of the matrix. This excess surface concentration resulted in a burst effect for drug release in acidic dissolution media with up to 30 per cent drug released in 2 min. This was followed by a more gradual release of drug and finally the release tended to tail off as the matrix became depleted of drug. The average t50 per cent release was 12min. Variable swelling of the matrix occurred during the first 20–30 min of dissolution which complicated the interpretation of release data. Treatment of the albumin spheres with spermaceti or paraffin wax tended to reduce swelling and increased the t50 per cent release to 33 min and 43 min respectively. Cross-linking of...
TL;DR: The authors studied the parameters of sustained released Tofizopam microcapsules, prepared by a melt-dispersion method, and the factorial design method proved to be very useful for examination of micro Capsules.
Abstract: The authors studied the parameters of sustained released Tofizopam micro-capsules, prepared by a melt-dispersion method. The parameters examined were the flowing rate, strength and dissolution characteristics. Dissolution curves were linearized by the RRSBW distribution. The factorial design method proved to be very useful for examination of microcapsules.
TL;DR: The drug permeability coefficients calculated according to an equation derived from Fick's first law of diffusion were found to increase with decreasing capsule size in both constant total capsules volume and constant total capsule surface area experiments.
Abstract: Inward permeation from the surrounding medium of phenobarbital through the wall of water-loaded ethylcellulose microcapsules was investigated as a function of capsule size under the conditions of constant total capsule volume and constant total capsule surface area. The experimental data obtained were analysed in terms of capsule wall density and drug partition coefficient. The drug permeability coefficients calculated according to an equation derived from Fick's first law of diffusion were found to increase with decreasing capsule size in both constant total capsule volume and constant total capsule surface area experiments. The wall density and the drug partition coefficient also exhibited the same trend. Based on these findings, it was concluded that the drug permeation through ethylcellulose microcapsule membrane occurs predominantly by a solution-diffusion mechanism.
TL;DR: Nonpareil seeds were loaded with sodium salicylate and enteric coated with organic solvent based systems including polyvinyl acetate phthalate, cellacephate (CAP), shellac, hydroxypropylmethylcellulose phthalates, or Eudragit L as film former to achieve best results.
Abstract: Nonpareil seeds were loaded with sodium salicylate and enteric coated with organic solvent based systems including polyvinyl acetate phthalate, cellacephate (CAP), shellac, hydroxypropylmethylcellulose phthalate, or Eudragit L as film former. Details of the pan coating procedure used were described. The CAP product showed optimum surface continuity when examined by scanning electron microscopy. The shellac product exhibited least aggregation during coating and consequently gave highest yields. Dissolution studies on the microcapsules in simulated gastric and intestinal media indicated that the CAP coated microcapsules had the most satisfactory enteric properties.
TL;DR: Stable liposome-type artificial red blood cells containing either an aqueous bromothymol solution or erythrocyte haemolysate were produced using carboxymethylchitin as a stabilizer, and the structure of the resulting vesicles was investigated by electron microscopy after freeze-fracturing, freeze-substitution and negative staining.
Abstract: Stable liposome-type artificial red blood cells containing either an aqueous bromothymol solution or erythrocyte haemolysate were produced using carboxymethylchitin as a stabilizer. The structure of the resulting vesicles was investigated by electron microscopy after freeze-fracturing, freeze-substitution and negative staining. The vesicles were not homogeneous but contained unilamellar and multilamellar structures. The maximum size was about 2μm; most vesicles were about 200–500 nm in size. The carboxymethylchitin did not yield a continuous layer but rather occurred in patches on the membrane surface probably forming a mesh-like layer over the entire liposome surface.
TL;DR: Significant synergism is demonstrated in the combined effects of these digestive agents in producing permeability of the vesicles to Dy3+ and changes in the 1H-n.m.r.s. spectroscopy spectrum indicate that the products of the enzymic hydrolysis and transmembrane lipid exchange are involved in the permeability mechanism.
Abstract: 1H-n.m.r. spectroscopy of small unilamellar phospholipid vesicles in the presence of the lanthanide probe ion Dy3+ has been used to study the permeability of these liposomes induced by the bile salts (glycocholate and glycodeoxycholate) and pancreatic phospholipase A2. A marked synergism is demonstrated in the combined effects of these digestive agents in producing permeability of the vesicles to Dy3 +. Changes in the 1H-n.m.r. spectrum of the vesicular phospholipid head-groups before permeability is induced, indicate that the products of the enzymic hydrolysis (lyso lipids and fatty acids) and transmembrane lipid exchange are involved in the permeability mechanism. The results are discussed in terms of the advantages of the use of n.m.r. techniques in the future design of liposomes for oral use.
TL;DR: To follow the pH within the microcapsule core during manufacture, pH indicators were encapsulated and the final pH was found to depend on the formulation used and could be controlled by the addition of acid.
Abstract: The application of nylon microencapsulation as a drug delivery system inherently demands that the microencapsulated matrix should not cause degradation of the encapsulated drug. The presence of alkaline hexamethylenediamine (HMD) in the microcapsule core will affect the final pH of the microcapsules and may influence the stability of some drugs. To follow the pH within the microcapsule core during manufacture, pH indicators were encapsulated. The final pH was found to depend on the formulation used and could be controlled by the addition of acid. Several other variables affecting the nylon wall formation were examined to determine optimum processing conditions. Increased agitation produced a decrease in microcapsule size. This cause an increase in nylon weight recovered. The increased recovery of nylon was due in part to nylon formation over a larger surface area. Varying the amounts of HMD and sebacyl chloride (SC) used also affected the total weight of nylon formed. In general, more nylon is recovered as the level of each reactant increases. However, the molar ratio of HMD:SC determined the total amount of nylon formed when SC was present in excess.
TL;DR: Dihydralazine sulphate was found to be governed by the core: wall ratio, microcapsule size, and the amount and kind of disintegrating agents, and dissolution kinetics were studied and evaluated.
Abstract: One of the principal uses suggested for the microencapsulation of pharmaceuticals has been the preparation of the sustained release dosage form. The finished microcapsules have usually been presented in the form of suspensions or gels, but in order to obtain greater sustained release effect a non-disintegrating tablet would be a better formulation.Dihydralazine sulphate (Nepresol) is a dihydralazine-1,4-phthalazine derivative and used as an antihypertensive drug. This work was planned to prepare sustained action preparations of dihydralazine sulphate by microencapsulation and by tabletted microcapsules.Microcapsules were prepared from the microcapsule fractions using biconvex punches with 0.81 cm diameter fitted into a single punch by hand compressor. Avicel PH 101 and lactose were used as disintegrating materials in tablets having 2 kg hardness.Dissolution from both suspended microcapsules and the tablets was studied using the XX basket method.A study of in vitro release for both the free and tab...
TL;DR: The kinetics of capsules growth during the preparation was discussed on the basis of the distribution of particle size and an increase in the atomization time of the ethylcellulose solution produced a more dense product with a prolonged release of the drug.
Abstract: Microcapsules containing isoniazid were produced by the fluidized bed method with ethylcellulose by varying the total atomization time. The kinetics of capsules growth during the preparation was discussed on the basis of the distribution of particle size. The quality of the capsules was evaluated using the particle size characteristics, the total content of ethylcellulose, the particle and wall density, and the time needed for the 50 per cent release of the drug. An increase in the atomization time of the ethylcellulose solution gave rise to an increase in the mean diameter of particles and the ethylcellulose content of capsules; it also produced a more dense product with a prolonged release of the drug. The release of the drug from tabletted microcapsules was further prolonged.
TL;DR: These albumin nanospheres can be used for studying the reticuloendothelial system, especially that of the liver, and the efficiency of labelling with 99mTc is higher than 97 per cent.
Abstract: A modified method is described for the preparation of albumin nanospheres for labelling with 99mTc by investigating the absorption behaviour of tin as a reducing agent on albumin nanospheres. These albumin nanospheres can be used for studying the reticuloendothelial system, especially that of the liver. The labelling method is very simple, and the efficiency of labelling with 99mTc is higher than 97 per cent.
TL;DR: The possibility of using microcapsules as a sustained dosage form of theophylline as well as a single-compartment model for absorption and elimination could explain the results found.
Abstract: The possibility of using microcapsules as a sustained dosage form of theophylline has been investigated. The release characteristics of two formulae were compared with microcrystalline theophylline. Urine samples were assayed using H.P.L.C. to separate the unchanged theophylline which was detected by its U.V. spectrum. A single-compartment model for absorption and elimination could explain the results found. Both microencapsulated formulations showed a significantly extended absorption time over that of non-encapsulated theophylline.
TL;DR: The anticancer drug Adriamycin was tested in vitro both in free form and encapsulated in negatively charged liposomes, finding that up to 45 per cent of the originally entrapped drug was released from the lipid vesicles over a 24-hour period.
Abstract: The anticancer drug Adriamycin was tested in vitro both in free form and encapsulated in negatively charged liposomes. [3H]-thymidine incorporation and a 72-hour survival test were used for the evaluation of cytotoxicity in a phagocytic human melanoma cell line and a non-phagocytic human ovarian carcinoma cell line. In each case, free Adriamycin induced greater cell damage than did liposomal drug. Stability tests of the liposomes used for subsequent cytoxicity studies under the exact conditions of the cell culture assay revealed that up to 45 per cent of the originally entrapped drug was released from the lipid vesicles over a 24-hour period.
TL;DR: In vitro dissolution studies of microencapsulated indomethacin showed that the USP paddle method was superior to theUSP basket method in that the drug release was higher and more uniform with the paddle.
Abstract: In vitro dissolution studies of microencapsulated indomethacin showed that the USP paddle method was superior to the USP basket method in that the drug release was higher and more uniform with the paddle. Simulated intestinal fluid (pH 7.2) was an appropriate medium to use for dissolution studies on prolonged-release microcapsules.
TL;DR: The method of evaluation of the permeability coefficient of microcapsule membrane from experimental data measured with a variable shearing interferometer is theoretically investigated and polystyrene and nylon 6,10 microcapsules are determined.
Abstract: The method of evaluation of the permeability coefficient of microcapsule membrane from experimental data measured with a variable shearing interferometer is theoretically investigated. The permeability coefficients of polystyrene and nylon 6, 10 microcapsules are determined by the evaluated method from the optically measured data for the non-stationary diffusion process of electrolyte.