Microglobule size, morphology and recovery of pectin-gelatin coacervates were investigated by McMullen and coworkers (1982). Coacervates were prepared by combining solutions of pectin and Type A gelatin in varying ratios at 45°C with stirring and adjusting the pH with NaOH solution. After 2min the pH was lowered with 0.5 N HC1 and after stirring for 30min, 5 ml of 37% formaldehyde solution were added. After cooling and decanting, the microcapsules were suspended in glycerin and then treated with an alcohol as the flocculating agent. The flocculated microglobules were filtered and washed with isopropyl alcohol and dried. At a coacervation pH of 3.8 the mean globule size increases from 2 to 10¡im when the pH of mixing was increased from 7 to 10. For solutions with equal pectin and gelatin concentrations, the maximum yield of the coacervate occurred at a colloid concentration of 2%. The maximum yield and microglobule diameter occurred at a pH of about 3.8 after coacervation, but depended upon the pH of mixing which ranged between 8 and 10. These changes were related to the ionization of gelatin and pectin and the viscosity of the microglobules. Increasing concentration of glycerin from 0 to 72% changed the morphology from spheres to ellipsoids. The formation of ellipsoids was attributed to dehydration of the coacervate and increasing intermolecular association as a result of decreasing dielectric constant. Isopropanol and 1-propanolol produced satisfactory microglobules, while other alcohols were not suitable.
In a subsequent paper, McMullen etal. (1984) encapsulated sulfame-razine with a gelatin-pectin coacervate. It was found that the drug should be added at the starting pH, that is, before coacervation takes place. The authors suggest that the drug is entrapped and the process is not a surface-active phenomenon as suggested for gelatin-acacia. Globules of various sizes with mean diameters 5.7, 9.2 and 25.5 /¿m containing 37-45% drug could be produced. The spherical shape of the microcapsules was maintained at drug loadings of <69% and <45% for 25 ¿tm and 10ftm microglobules, respectively. A small suppression of coacervate yield occurred as the drug to colloid ratio increased, which was attributed to salt suppression by the drug. Complete digestion of the microglobules was observed with gastric and intestinal juice only. No apparent morphological change in the microcapsule was observed by extraction with 0.1 m HC1 or 0.1 m NaOH or water. Several other drugs such as phénobarbital, hydrocortisone acetate and cod liver oil which have low solubility in water and small particle size were successfully encapsulated.
In a further paper, Bechard and McMullen (1986) investigated the dissolution times of gelatin-pectin microglobules as a function of formaldehyde concentration and reaction times. It was found that the dissolution half-lives, in terms of the number of microglobules, can be controlled over a period from 2.7 to 751 min in a solution of sodium chloride and polyoxy-ethylene sorbitan monolaurate. A decrease in dissolution rate of the microcapsules was observed with aging of the product stored at ambient conditions.
The gelatin-pectin coacervate has also been used to encapsulate indometha-cin. Ku and Chin (1989) found that the optimum pH and pectin : gelatin ratio for microcapsules was 3.8 and 1.2 respectively. As the concentration of colloid solution increased, the wall thickness increased. The 50% release time for indomethacin prepared from 1, 1.5 and 2% colloid solutions were 3, 5 and 6 min, respectively, while that of indomethacin powder was 50 min.
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