Preparation of large porous biodegradable microspheres by using a simple double-emulsion method for capreomycin sulfate pulmonary delivery.
The aim of this work was to evaluate if a simple double-emulsion method could be used for developing a new formulation of large porous microspheres (MS) potentially useful for capreomycin sulfate (CS) pulmonary delivery. Poly(DL-lactide-co-glycolide) was used for MS preparation. A simple W/O/W double-emulsion/solvent evaporation preparation method was employed and MS were characterized by UV spectrophotometry, particle size, and scanning electron microscopy. A computer-generated response surface method (RSM) was employed to evaluate % drug content, volume mean diameter (VMD), and span upon variation of two numeric and two categorical factors. MS size distribution was found to be strongly affected by the homogenization method and the type of emulsifier employed. Mean diameters ranged from 1 to 20 microm. The MS presented a proper morphology, with a highly porous interior and a rough surface. Peptide content ranged between 1 and 20%. The region of optimality was referred to as a low VMD and span values, and a high drug content. The best results were found when using a 20% loading, 19.8-3.2 dichloromethane/acetone ratio, ultraturrax mixing, and HPMC as emulsifier. The double-emulsion method allowed the preparation of CS loaded large porous MS having suitable characteristics to match respirability requirements. The use of RSM helped to establish the conditions to obtain formulations potentially useful for a possible CS pulmonary delivery, by using a simple preparation method with a consistent time, cost, and material saving.
Giovagnoli
Stefano
S
Department of Chemistry and Technology of Drugs, Università degli Studi di Perugia, Via del Liceo 1, 06123 Perugia, Italy. eureka@unipg.it
Blasi
Paolo
P
Schoubben
Aurelie
A
Rossi
Carlo
C
Ricci
Maurizio
M
D000096:Acetone / Q000737:chemistry; D000280:Administration, Inhalation; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000737:chemistry*; D002207:Capreomycin / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions; D065347:Hypromellose Derivatives; D019344:Lactic Acid / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008752:Methylene Chloride / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008956:Models, Chemical; D015233:Models, Statistical; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties; D013678:Technology, Pharmaceutical; D014867:Water / Q000737:chemistry
D000904:Antibiotics, Antitubercular; D004337:Drug Carriers; D045703:Emulsifying Agents; D004655:Emulsions; D009821:Oils; D011108:Polymers; D014867:Water; D002207:Capreomycin; D000096:Acetone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D065347:Hypromellose Derivatives; D008752:Methylene Chloride; D008747:Methylcellulose