Microencapsulation of indomethacin by gelatin-acacia complex coacervation in the presence of surfactants.

Gelatin-acacia microcapsules containing indomethacin were prepared by a complex coacervation method. To improve the wetting of hydrophobic core material different surfactants, cationic benzalkonium chloride, anionic sodium lauryl sulphate (SLS) or non-ionic polysorbate 20, were used. The effects of surfactants on microencapsulation were investigated at concentrations below, at and above their critical micelle concentration (CMC) using three different stirring speeds (200, 310 and 420 rpm). A considerable fraction of the core was leached out during the dehydration of microcapsules with isopropanol when the capsules were prepared without surfactant, and especially with SLS. SLS was noted to be an unsuitable surfactant for this process of microencapsulation, and this was considered to be due to ionic complexes, solubilization of gelatin and too-effective spreading of small coacervate droplets. Benzalkonium chloride enhanced encapsulation at concentrations below and at CMC, but above CMC the encapsulation was slightly decreased due to too-effective spreading of coacervate. Polysorbate 20 enhanced encapsulation with all the concentrations allowing for the formation of intact-walled microcapsules. All the microcapsules reduced in size with increasing stirring speed. The two lowest concentrations of benzalkonium chloride and all the concentrations of polysorbate 20 increased microcapsule size due to a greater amount of the colloids being available in formation of thicker walled microcapsules. The dissolution of unencapsulated indomethacin was very slow, but the drug was released quickly from all the microcapsules whether or not any type of surfactant was used. A hydrophilic wall of gelatin-acacia microcapsules in itself ensured quick wetting of hydrophobic indomethacin.

The influence of ageing on the release of hydrocortisone from o/w creams.

The influence of ageing on the release of hydrocortisone from o/w creams containing ionic and nonionic emulgators and different amounts of water was investigated over a period of 48 weeks. The influence of ageing was dependent on the type of emulgator and the amount of water in the cream. Up to 12 weeks of storage, ageing affected the creams containing ionic emulgators by retarding the release of hydrocortisone; after that, hydrocortisone release was enhanced and the release profile also changed. For the creams containing 60% water, the effects of ageing differed slightly from the creams containing 40% or 80% water. These findings can be explained by particle growth and agglomeration but changes in the microstructure of the creams may also be important. Creams containing nonionic emulgators were only slightly affected by ageing.

Effect of water content and type of emulgator on the release of hydrocortisone from o/w creams.

The release of hydrocortisone was determined in vitro from o/w-creams containing an anionic (sodium lauryl sulphate), a cationic (cetrimide) or a nonionic (cetomacrogol 1000) surfactant as emulgator and different amounts of water. The solubility of hydrocortisone in water-emulgator systems and the solubilizing capacity of these emulgators for hydrocortisone were also determined. The release of hydrocortisone from creams containing emulgators increased in the same order as the solubilizing capacity of these emulgators for hydrocortisone, which indicates how important the concentration of dissolved hydrocortisone in the cream is for release. The effect of water content on the release of hydrocortisone was also dependent on the emulgator used. With a nonionic emulgator, release was enhanced slightly as the water content in the cream increased. In the case of ionic emulgators, release of hydrocortisone was retarded as the amounts of water in the cream increased up to 60% water content; above this, the release was enhanced, probably owing to changes in the liquid crystalline microstructure of the cream.

Parabens as antimicrobial preservatives in creams.

Antimicrobial effectiveness of methylparaben and a mixture of methyl- and propylparabens in an oil-in-water cream was studied. How the number of microbes and inclusion of nutrients into the cream affect the effectiveness of these compounds were also investigated, as well as the survival of test microbes in the cream without preservatives. Survival of microbes and antimicrobial effectiveness of parabens against the microbes in the cream were dependent on the species and number of microbes present and also on the amount of nutrients available for the microbes. In spite of the large amount of water, the cream studied did not readily support microbial growth unless the number of microbes was large or nutrients were added. Parabens were not effective antimicrobial agents against the yeast studied. The bacterial species showed different sensitivities to parabens. A mixture of methyl- and propylparabens was more effective than the methylester alone.

Microbiological purity testing of semisolid topical preparations.

The reliability of the poured plate method for purity testing of three different creams and an anhydrous ointment was studied. The ability of some nonionic surfactants to elute the microbes from the semisolid preparations to water phase and possible detrimental effects of these surfactants on the microbes was especially investigated. The method was used to test the effect of preparation temperature and of storage on the number of microbes in creams. Nonionic surfactants studied did not generally harm the bacteria. Variation was, however, found between different bacterial species and even bacterial strains. The surfactants studied eluted bacteria quantitatively from the water-containing creams but not from the water-free ointment. The concentration needed for quantitative elution of microbes was dependent on the surfactant used, being lower for Brij 58 than for Tween 80. Heating of the phases up to 60 or 70 degrees C for a short time during the preparation of the creams does not ensure the microbial purity of the preparation. In creams made at 80 degrees C, however, all the bacteria had died, only the spores of B. subtilis survived this temperature. After two months storage at 5 degrees C, all microbes tested were still detected in creams. There were, however, differences in survival of different microbes. None of the bacteria multiplied during the storage, but decreased slightly in number.