Acrylates

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Hydrophobic compounds have been encapsulated with 2-diethylaminoethyl methacrylate-methacrylic acid-styrene copolymer latex by Ushiyama (1979). For example, castor oil was emulsified in water containing an anionic surfactant, Emal A, to a particle size of 30-50 ^m. The pH was adjusted to about 9 and the polymer added, which has an isoelectric point of 7.2, and the pH adjusted to 9-10 with NaOH. After acidifying to a pH of 5-5.5 to form the capsules, the product was spray dried.

Donbrow etal. (1984) encapsulated potassium dichromate and paracetamol with poly(methyl ethyl methacrylate) (Eudragit Retard). The polymer and polyisobutylene were dissolved in chloroform and the core material was suspended in the solution. Cyclohexane containing polyisobutylene was added at a controlled rate and coacervate droplets formed which encapsulated the core material. A decrease in the rate of addition of the nonsolvent caused a decrease in the rate of release of the core material; this was attributed to structural changes as the core concentration was almost constant at about 80%. At high addition rates of the non-solvent, the microcapsules had polymer spheres attached to the surface - thus the effective wall thickness was reduced and the release rate increased. As more nonsolvent was added, more polymer came out of solution - thus the percentage of core material in the microcapsules decreased and the release rate decreased. It was also found that smaller particles gave faster release rates.

Chun and Shin (1988) encapsulated aspirin with Eudragit RS polymer from a solution of chloroform with polyisobutylene dissolved in cyclohexane. The polyisobutylene functioned as a coacervation-inducing agent and gave smooth microcapsules with less aggregation. By increasing the proportion of the wall material, particle size and wall thickness, and the concentration of paraffin wax in the cyclohexane as a sealant, a product with sustained release characteristics could be obtained. Release was independent of pH of the medium and the mechanism of drug release from both non-sealed and sealed microcapsules appeared to fit Higuchi matrix model kinetics. The aspirin microcapsules were more stable than free drug in a solution of NaHC03.

Eudragit L 100, a copolymer of methacrylic acid and methylmethacry-late which is insoluble in acid but soluble in alkaline solution, was used to encapsulate aspirin (Okor, 1988). The drug and polymer were dissolved in 95% ethanol and the solution was evaporated to dryness. The product was crushed and passed through a sieve and the fraction between 710 pm and 500 fim was collected. Dissolution was retarded in acidic medium, but enhanced in neutral medium. The author suggests that drug-polymer attractions are possibly stronger than drug-drug attractions, thus partly accounting for the delayed release in the acid medium. In the alkaline medium the polymer is soluble and readily liberates the aspirin.

Okor (1989) prepared colloidal solutions of ethyl acrylate (trimethyl ammonium) ethyl acrylate chloride-methyl methacrylate copolymer using ethanol as a solvent and water as the non-solvent. Stability of the dispersion to electrolytes such as NaCl and Na2S04 increased considerably with an increase in the polymer cation content. The polymer dispersions were most sensitive to Na2S04 and least sensitive to NaCl. In 1990 Okor encapsulated the drug salicylic acid with acrylate-methacrylate copolymers. The drug and polymer were dissolved in ethanol and excess water, the non-solvent, was added in the presence of a flocculating agent, NaCl. The dried coacervates were compressed into tablets or placed into capsules. It was found that drug release rates decreased exponentially with increase in polymer concentration in the coacervate, but increased exponentially with an increase in polymer cation content at a constant polymer concentration of 20% w/w. The increase in release rate was associated with an increase in polymer 'swell-ability'. Drug release rates from tablets were retarded compared with those from capsules; this was believed to be due to poor disintegration of the tablets.

A coacervation technique using an acrylate-methylacrylate copolymer was used to form an aqueous based coating system consisting of the water-insoluble copolymer and sucrose in varying ratios to coat matrix cores by Okor etal. (1991). Drug release rates increased as the concentration of the sucrose increased in the film coating. Doubling the coating thickness from 75 fim introduced a lag time for release of the model drug salicylic acid from 0.5 to 2.5 h depending upon the amount of sucrose. Overall, however, the release rates were hardly affected by the coating thickness.

Aqueous dispersions prepared by coacervation of Eudragit RL 100 and RS 100 were prepared by Okor (1991). A lower viscosity and higher gel point was observed with Eudragit RL 100. This phenomenon was explained by the higher degree of mutual repulsion of the cationic charges in Eudragit RL 100 compared with Eudragit RS 100. The fluidity of aqueous dispersion of these two polymers suggests their use in film coating processes.

Eudragit RS 100 polymer dissolved in chloroform was used to coat zipeprol hydrochloride. Cyclohexane containing polyisobutylene effected coacervation. The mechanism of drug release from the microcapsules appeared to fit the Higuchi matrix kinetics. Plasma concentration time curves suggested that the microcapsules can be used as a sustained release product (Yong and Kim, 1988).

Ferrous fumarate and ferrous sulfate were encapsulated by evaporation and various other methods using different Eudragit polymers. In vitro dissolution studies indicate the release was linear, but there was an inflection point that separates the initial fast release from the later, slower phase. In some cases a biphasic pattern was noted for larger size microcapsules, whereas a monophasic pattern was observed with small microcapsules. Particle size was the most important factor in determining the dissolution. The nature of the polymer and integrity of coating had a minor influence on dissolution (El Shibini etal., 1989).

Kim etal. (1989) encapsulated a complex of dextromethorphan hydro-bromide and a strong cation-exchange resin with Eudragit RS by phase separation using a non-solvent. It was found that the release rate from the coated complex could be controlled by the amount of coating material. The effect of pH and the ionic strength on the release rate of the drug was also studied.

Sprockel and Price (1990) encapsulated the complex of chlorpheniramine maleate and a carboxylic acid cation-exchange resin. The complex was suspended in an acetone solution of polymethyl methacrylate, then emulsified in liquid paraffin containing various additives. After 12 h of stirring to permit the evaporation of the solvent, the microcapsules were collected, washed with hexane and dried. Several parameters and additives were tested and it was found that: (a) larger microcapsules were obtained if the concentration of the polymer was increased; (b) fine particles of bentonite, Veegum, carbon black or emulsion stabilizers, reduced the microcapsule size at 3% concentration, but increased the size at 6% owing to incorporation into the microcapsules; (c) silicone fluid 60 000 cp was more effective in reducing the microcapsule size than silicone fluid 50 cp; (d) magnesium stearate, glyceryl monostearate and stearyl alcohol reduced the microcapsule size; (e) formulations with higher coat to core ratios resulted in slower release of the drug from the microcapsules; (f) larger microcapsules released the drug at a slower rate than did smaller microcapsules.

Alex and Bodmeier (1990) encapsulated pseudoephedrine hydrochloride by preparing a solution of the drug in water and then preparing an emulsion in a solution of poly(methyI methacrylate) in methylene chloride with the use of a sonicator. This primary w/o emulsion was added to the external phase - water containing 0.25% polyvinyl alcohol) as stabilizer - with stirring at 1500r.p.m. in a small container with baffles for lOmin to give a w/o/w emulsion. The microcapsules were filtered and rinsed with water. Sonication resulted in the smallest droplet size and highest drug content. As the drug was not soluble in the polymer solution, it could not diffuse to the external aqueous solution. The method had good batch-to-batch reproducibility with respect to drug loading. The yield was above 95% and the particle size ranged from 50 to 500 ^m. The drug content of the microspheres increased with drug loading, increasing amounts of solvent, polymer, and polymeric stabilizer. This last factor was attributed to an increase in the thickness of the adsorbed layer of the polymeric stabilizer and an increase in viscosity close to the droplet surface, resulting in a reduction in the rate of solvent and drug diffusion across the droplet interface into the continuous phase. The drug content decreased with increasing stirring time, increasing pH of the continuous phase and increasing volume of the internal and external aqueous phases.

Theophylline was encapsulated with Eudragit RS 100 using a solution of the polymer, and polyisobutylene in chloroform (Chattaraj et al., 1991). Phase separation and rigidization of the deposited polymer was effected by using cold «-hexane. Polyisobutylene below 5.5% w/w did not produce uniform microcapsules, but aggregates. The drug content of the microcapsules was at maximum at 5.5% w/w of polyisobutylene at a fixed core to coat ratio. High percentages of polyisobutylene decreased the yield of the product. Dissolution at 37°C with increasing pH indicated that, as the core to coat ratio increased, the rate of dissolution also increased. As the percentage of polyisobutylene was increased in the preparation of microcapsules, the rate of release decreased. Bioavailability studies in rabbits indicated that prolonged release was obtained.

Badawi etal. (1991) encapsulated theophylline with Eudragit E and Eudragit L by non-solvent techniques. The best method to coacervate the drug is by using Eudragit E while the drug is dispersed in solution by the addition of a non-solvent. Eudragit E had a higher affinity for the drug and increased the surface drug by entrapment of the drug within the coat. Eudragit L formed a better barrier to the drug, but the microcapsules were less than satisfactory.

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