چکیده (انگلیسی):

This paper describes the formulation
of a biodegradable microparticulate drug delivery
system containing clodronate, a bisphosphonate
intended for the treatment of bone diseases.
Microspheres were prepared with several poly(D,Llactide-
co-glycolide) (PLGA) copolymers of various
molecular weights and molar compositions and 1
poly(D,L-lactide) (PDLLA) homopolymer by a waterin-
oil-in-water (w/o/w) double emulsion solvent
evaporation procedure. Critical process parameters
and formulation variables (ie, addition of stabilizing
agents) were evaluated for their effect on drug
encapsulation efficiency and clodronate release rate
from microparticles. Well-formed clodronate-loaded
microspheres were obtained for all polymers by
selecting suitable process parameters (inner water/oil
volume ratio 1:16, temperature-raising rate in the
solvent evaporation step 1°C/min, 2% wt/vol NaCl in
the external aqueous phase). Good yields were
obtained in all batches of clodronate microspheres
(above 60%); drug encapsulation efficiencies ranged
between 49% and 75% depending on the polymer
used. Clodronate release from all copolymer
microspheres was completed in about 48 hours, while
those from PDLLA microspheres required about 20
days. The change of microsphere composition by
adding a surfactant such as Span 20 or a viscosing
agent such as carboxymethylcellulose extended the
long-term release up to 3 months. Clodronate was
successfully entrapped in PLGA and PDLLA
microspheres, and drug release could be modulated
from 48 hours up to 3 months by suitable selection of
polymer, composition, additives, and manufacturing
conditions.