ABSTRACT
Previous methods of microencapsulation are unable to process particles smaller than 100 microm without organic solvents or the use of multistep processes. The present study investigates the feasiblity of a one-step spray-drying process to microencapsulate erythromycin and clarithromycin, antibiotics known to have an unpleasant, bitter taste. Mixtures of clarithromycin (5% by weight) or erythromycin (30% by weight) with a biodegradable polymer were prepared and spray-dried under specific conditions of temperature and turbine speed. This process resulted in the microencapsulation of 80% of each drug as determined by high pressure liquid chromatography. Particle size ranged from 1 to 80 microm as determined by electron microscopy. These data show that microencapsulation of macrolides using a spray-drying technique is feasible. Spray-drying microencapsulation might be useful in the formulation of palatable oral suspensions of bitter tasting drugs.
Subject(s)
Anti-Bacterial Agents/chemistry , Clarithromycin/chemistry , Erythromycin/chemistry , Anti-Bacterial Agents/administration & dosage , Capsules , Chemistry, Pharmaceutical/methods , Chromatography, High Pressure Liquid , Clarithromycin/administration & dosage , Drug Compounding , Erythromycin/administration & dosage , Microscopy, Electron , Particle SizeABSTRACT
The thermoresistance of a cold-adapted subtilisin dried by spray-drying was studied. Proteolytic activity of this enzyme was measured before and after spray-drying. Without chemical additives, spray-drying yields ranged from 2-13%. The use of arabic gum and lactose in the composition of the enzyme solutions allowed the strengthening of the enzyme structures and increased water mobility in the product. Increase of water mobility led to a shorter residence time of the product in the spray-drier and a net yield increase was obtained (yield higher than 50%). The effect of two selective mutations on the thermoresistance to spray-drying of the cold-adapted subtilisin was also investigated. Mutation T85D (introduction of an additional link with an ion Ca2+ necessary for enzyme activity, by substitution of Asp for Thr 85) had no effect on the thermoresistance of the subtilisin to spray-drying. Mutation H121W (introduction of an additional aromatic link by substitution of Trp for His 121) reduced the drying yield from 66% (not modified subtilisin) to 52%. This higher thermosensitivity could be explained by an increase of the hygroscopic character of the modified subtilisin (mutation H121W).
