PREPARATION, CHARACTERIZATION AND IN-VITRO DRUG-RELEASE OF POLY-EPSILON-CAPROLACTONE AND HYDROXYPROPYL METHYLCELLULOSE PHTHALATE KETOPROFENLOADED MICROSPHERES
M. Guzman et al., PREPARATION, CHARACTERIZATION AND IN-VITRO DRUG-RELEASE OF POLY-EPSILON-CAPROLACTONE AND HYDROXYPROPYL METHYLCELLULOSE PHTHALATE KETOPROFENLOADED MICROSPHERES, Journal of microencapsulation, 13(1), 1996, pp. 25-39
Citations number
25
Categorie Soggetti
Pharmacology & Pharmacy","Chemistry Applied","Engineering, Chemical
Ketoprofen was encapsulated within poly-epsilon-caprolactone (PCL) and
hydroxypropyl methylcellulose phthalate 50 (HPMCP50) microspheres (MS
). Scanning electron microscopy (SEM) studies showed spherical particl
es without surface crystal formation and differential scanning calorim
etry (DSC) supported these results. MS of PCL or HPMCP50 had a mean pa
rticle size of 10.7 +/- 2.2 and 10.9 +/- 2.0 mu m respectively, wherea
s a mixture of these polymers increased the MS particle size to 30 mu
m. Greater incorporation efficiencies were found for HPMCP50 MS (98.1
+/- 0.7%). MS of PCL and HPMCP50 mixtures showed a decreased drug entr
apment as the amount of PCL was increased (96.0 +/- 0.2 for 25% PCL, 9
5.6 +/- 1.8 for 50% PCL, 80.2 +/- 0.7 for 75% PCL and 78.9 +/- 9.0 for
100% PCL). Size exclusion chromatography (SEC) studies revealed a wea
k interaction between ketoprofen and PCL and some polymer degradation
was found during HPMCP50 MS storage, probably by breaking of the phtha
lic anhydride bond to be anyhydroglucose backbone. Four types of cryop
rotectors (glucose, trehalose, mannitol and sorbitol, at 5 and 10% W/V
) and two freezing conditions (-196 and -20 degrees C) were evaluated
in freeze-drying studies. For HPMCP50, the sizes of MS after reconstit
ution of liophylizates were nearly the same as the initial ones. For P
CL MS only, those formulations with sorbitol or glucose at 10% and fro
zen at -196 degrees C showed acceptable results. In contrast to the ra
pid release rate of ketoprofen from PCL MS as a result of carrier poro
sity (80% released within 15 min), the release from HPMCP50 MS could b
e controlled by means of pH (40% released in the first 15 min in simul
ated gastric fluid and nearly 100% ketoprofen delivered in the same ti
me in simulated intestinal fluid).