Resultant Microcapsules Research Articles

A novel sustained-release formulation of insulin with dramatic reduction in initial rapid release

To ensure a strictly controlled release of insulin, a preparation method for insulin-loaded microcapsules was designed. Microcapsules were prepared with an injectable, biodegradable polymer composed of co-poly( d, l-lactic/glycolic) acids (PLGA) (mean molecular weight 6600, LA/GA ratio 50:50). Morphological examination using scanning electron microphotography demonstrated spherical particles with a main diameter of 15–30 μm. When 3% insulin-loaded PLGA microcapsules were administered subcutaneously as a single dose (250 U/kg) to streptozotocin-induced hyperglycemic rats, plasma insulin levels increased and were sustained at levels showing hypoglycemic effects. When glycerin, ethanol, or distilled water was used throughout the preparation procedure, the resultant microcapsules dramatically reduced the initial burst. The formulation in which glycerin was added to an oil phase containing PLGA, insulin, and ZnO increased plasma insulin levels to 86.7, 108.4, and 84.9 μU/ml at 1, 2, and 6 h, respectively. The levels remained at 36.2–140.7 μU/ml from day 1 to day 9. The AUC 0–24 h/AUC 0–336 h ratio was calculated to be 9.7%. The formulation prepared without additives gave such a rapid insulin release that animals receiving it became transiently hypoglycemic.

Characterization of ovalbumin-containing polyurethane microcapsules with different structures

Ovalbumin (OVA)-containing polyurethane microcapsules were successfully prepared by a reaction between toluene diisocyanate (TDI) and different polyols such as glycerol, ethane diol, and propylene glycol. The structural and thermal properties of the resultant microcapsules and the release profile of the OVA from the wall membranes were studied. In conclusion, the microcapsules from the glycerol showed the highest thermal stability, with the formation of many hydrogen bonds. From the data of release profiles, it was confirmed that the particle size distribution and morphologies of microcapsules determined the release profiles of the OVA from the wall membranes.

Morphologies and release behavior of polyurea microcapsules from different polyisocyanates

Polyurea microcapsules were prepared by emulsion polymerization after adding an aqueous solution with poly(vinyl alcohol) as protective colloid into an organic solution with migrin oil as core material, 1,4-diamino anthraquinone (DAA) as penetrator, and different molar ratios of isophorone diisocyanates (IPDI) and toluene diisocyanates (TDI) as wall materials. The effects of diisocyanate types on the morphologies and release behavior of the resultant microcapsules were investigated. The transmittance (%) of the completely dissolved microcapsule in dimethyl acetamide (DMAc) by UV/visible spectrophotometer decreased with the content of aliphatic IPDI in the wall by increasing the wall thickness due to its inferior reactivity compared to aromatic TDI. Also in SEM images, these polyurea microcapsules from higher TDI content had rougher surfaces. In conclusion, the release profiles of the microcapsules in extraction solution showed that release rate of DAA depended on the roughness of the microcapsules.

Novel technology for the preparation of sterile alginate-poly-l-lysine microcapsules in a bioreactor.

The purpose of this study was to develop a method that may be suitable for the commercial manufacture of sterile alginate-polylysine-alginate microcapsules in a bioreactor. A Turbotak atomizing device in conjunction with a Bellco Bioreactor was used to prepare sterile microcapsules. Aseptic procedures were followed using sterilized equipment and materials. Sodium alginate solution was sprayed into calcium chloride solution using the Turbotak, with nitrogen as the atomizing gas. The resultant gelled alginate microcapsules were coated with polylysine and alginate to produce alginate-poly-l-lysine microcapsules. In-process contamination of the atomizing gas and microcapsules was investigated using modified USP sterility tests. Microcapsule size was determined using a light blockage technique (Accusizer) which measures both number and volume weighted mean diameters. The microcapsules prepared passed a modified USP sterility test, and the Bellco Bioreactor was found to minimize the possibilities of environmental contamination and therefore enhanced operator safety. The flow rate of the atomizing gas was determined to significantly alter number and volume weighted mean microcapsule diameters. Statistical analysis indicated that the number weighted mean diameters in conjunction with the volume weighted mean diameters can be used to detect batch-to-batch changes in microcapsule diameters. In conclusion, the modified Bellco Bioreactor offers a novel approach for producing sterile alginate-polylysine microcapsules on a laboratory scale.

Micromeritic Properties of Nitrofurantoin Microcapsules

AbstractIn our previous study, we have prepared nitrofurantoin microcapsules using carboxymethylcellulose (CMC) and aluminium sulphate by a coacervation technique. In the present study, the micromeritics of these microcapsules were investigated in terms of standardization of the crude materials employed, the microcapsules product and the dosage forms prepared from these microcapsules. The microcapsules were prepared with a 1:1 core: wall ratio and sieved into three particle sizes. Both the micromeritic properties of the pure drug and the polymer were studied by determining their bulk volume and weight, tapping volume and weight, fluidity, angle of repose, weight deviation, particle size distribution, density and porosity, The particle size range went from approximately 250μm to 3000μm with a peak between 900μm and 1350μm. The results indicate that the flowability and the particle size of the resultant microcapsules were much increased compared with the raw materials. As the microcapsule size increases the...

Microencapsulation within crosslinked polyethyleneimine membranes.

A microencapsulation technique is proposed involving the formation of a polyethyleneimine (PEI) membrane crosslinked by an acid dichloride. The membranes were formed at pH 8 in a non-polar solvent, conditions which are better suited for the encapsulation of biocatalysts or fragile biochemicals than those using polyamide membranes. The mean diameter and size distribution of the PEI microcapsules were similar to that observed with nylon membranes. The resultant microcapsules were spherical, free-flowing with a strong membrane. The mass of membrane was seen to be independent of the reaction time (1-4 min), insensitive to the PEI concentration and proportional to the concentration of crosslinking agent.

Preparation and characteristics of microcapsules containing enoxacin by one continuous process of agglomeration and microencapsulation.

A novel microencapsulation technique was carried out with the phase separation of Eudragit RS from the wet spherical agglomeration (WSA) system by non-solvent addition. To elucidate the characteristics of microcapsules the spherical agglomerates containing enoxacin (ENX), lactose or Avicel which are different in their affinity to water (i.e. insoluble, soluble or absorbable properties, respectively), were prepared as core particles in an acetone/n-hexane mixture (volume ratio 3/7) by a WSA technique. The size of all kinds of spherical agglomerates was controlled by the amount of bridging liquid (ammonia water or distilled water) used. In the microencapsulation process encapsulation was performed efficiently at 400-600 rpm. Avicel agglomerates could be coated up to 30 per cent with Eudragit RS with less aggregation. Various additives were compared as additions into the system to avoid the aggregation of encapsulated particles. Addition of more than 3 per cent magnesium stearate based on the core weight in the system, before or at the same time as phase separation of Eudragit RS occurred, resulted in low aggregation of microcapsules for spherical agglomerates containing ENX or lactose. In formulating a water-absorbable excipient such as Avicel in the agglomerates of ENX, adding some 10 per cent Eudragit RS-dichloromethane solution into the WSA system, and using magnesium stearate as a protective agent, the resultant microcapsules could be obtained efficiently without aggregation, showing sustained release of ENX depending on coating level.

Metabolic activity of CHO fibroblasts in HEMA–MMA microcapsules

Chinese hamster ovary (CHO) fibroblast cells were microencapsulated in polyacrylate membranes (HEMA-MMA: 75% HEMA) via an interfacial precipitation process. The CHO cells were observed to grow in large aggregates, attached to each other instead of to the capsule wall. When CHO cells were encapsulated at high density (4 x 10(6) cells/mL), the initial metabolic activity in microcapsules, as determined by the MTT assay, correlated with the polymer-cell extrusion ratio, presumably because of the dependence of encapsulation efficiency on the relative flow rates. However, there was a large variation in the metabolic activity among individual microcapsules throughout the present study. Capsules with low encapsulation efficiency (at a "seeding" density of 4 x 10(6) cells/mL) exhibited a rapid increase in the metabolic activity during the following week. When CHO cells were encapsulated at low density (4 x 10(5) cells/mL), there was only a small increase in the metabolic activity. Only a small fraction ( approximately 5%) of the capsules exhibited a high level of metabolic activity and 40% of the capsules exhibited undetectable metabolic activity even after 2 weeks. We conclude that CHO cells, which served as model cells, survive the encapsulation process and retain an active metabolic state once enclosed by the HEMA-MMA membranes. However, the resultant microcapsules are extremely heterogeneous in the amount of retained metabolic activity.

Microencapsulation of a slightly soluble drug by surface neutralization method using an enteric polymer.

Succeeding our previous study on enteric microencapsulation by surface neutralization method for acidic drugs, a new means of application was developed for the encapsulation of non-acidic drugs. Indomethacin was chosen as a model drug in this study because of its low solubility in water and non-acidicity. Carboxylmethylethylcellulose was used as enteric polymer as previously. Indomethacin was not encapsulated as it was, but the encapsulation could be done using its core granules added with an organic acid. Thus, the influences of preparation temperature, species of organic acid and its concentration in the cores as well as the species of binder on the properties of resultant microcapsules were examined

Drug Release Properties of the Microcapsules of Adriamycin Hydrochloride with Ethylcellulose Prepared by a Phase Separation Technique

AbstractAdriamycin hydrochloride was microencapsulated with ethylcellulose by a phase separation method to develop a prolonged release dosage form. Polyisobutylene (PIB) was used as a coacervation-inducing agent to control the particle size and drug release rate of the resultant microcapsules. With increasing the concentration of PIB (1 to 3 %) the average diameter of the microcapsules decreased, due to the fact that the microcapsules were discreted to a single microcapsule. At low concentration of PIB, the resultant microcapsules were agglomerated, which resulted in increasing the size. The microcapsules prepared with PIB 2 % prolonged desirably the drug release from the microcapsules. A little size effects of the microcapsules on the drug release rate was found for the microcapsules with PIB 2 % and 3 %.

Electrophoretic Properties of Sulfamethoxazole Microcapsules and Gelatin-Acacia Coacervates

The electrophoretic properties of sulfamethoxazole microcapsules and the coacervates prepared by gelatin-acacia coacervation were investigated. The effects of the parameters in the microcapsule preparation, such as the coacervation pH, amount of formaldehyde used for hardening, and drying method of the coacervates, on the ζ-potential of the resultant microcapsules were clarified. The Büchner effect was observed in coacervates in an electric field, which indicated that the coacervate wall was flexible. The ζ-potential versus pH curves of the coacervates appeared on the upper side of the plain sulfamethoxazole, while those of the microcapsules dried conventionally shifted to the lower side due to denaturation of the gelatin in the microcapsule wall, which occurred during drying. Spray drying increased the denaturation of gelatin, which imparted a negative charge to the spray-dried microcapsules. Formalization of the coacervates refined the electrophoretic behavior of the microcapsules, depending on the amount of formaldehyde used. The ζ-potential of the plain sulfamethoxazole also was measured in the simulated coacervation solution to analyze the mechanism of coacervation electrophoretically.