ABSTRACT
The aims of the present study were to prepare spray-dried polymeric nanocapsules (NC) and nanospheres (NS) from poly(epsilon-caprolactone) (P epsilon C) suspensions containing diclofenac (DIC) and to determine the physicochemical properties of the formulations. NC or NS suspensions were prepared by interfacial deposition of the polymer. DSC-thermograms of raw materials and NC or NS suspensions (evaporated or spray-dried) were obtained using a PL-DSC. Spray-dried powders were prepared by addition of 3% (w/v) Aerosil 200 into suspensions of NC or NS. These mixtures were fed into a spray-dryer. DIC was assayed by HPLC. NC and NS spray-dried powders were examined under SEM (Jeol Scanning Microscope, JSM-5800). NC and NS suspensions had acceptable diameter, 340 and 247 nm respectively. The yields of NC and NS spray-dried powders were 80% and 75% and the recovery of the DIC was 99% and 93%, respectively. The melting peak of P epsilon C in NC and NS was observed at a temperature about 10 degrees C lower than in the raw material. In the NC thermograms the maximum of the oil (Miglyol 810) melting peak (+1.6 degrees C) was lowered about 7 degrees C. For spray-dried NC formulations, the SEM analyses of powders showed spherical microparticles of silicon dioxide, covered by nanoparticles (300 nm), while for spray-dried NS formulations the microparticles presented a rugged surface at the same magnification.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Diclofenac/chemistry , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Calorimetry, Differential Scanning , Caproates , Capsules , Chemical Phenomena , Chemistry, Physical , Colloids , Diclofenac/administration & dosage , Electrochemistry , Excipients , Lactones , Microscopy, Electron, Scanning , Microspheres , Particle Size , Powders , SuspensionsABSTRACT
To prepare spray-dried powders of poly(D,L-lactic acid) (PLA) or poly-epsilon-caprolactone (P epsilonC) from colloidal suspensions containing indomethacin (IND) using benzyl benzoate (BnB), nanocapsules (NC) were prepared by nanoprecipitation. To select the best NC formulations, increasing drug concentrations were tested (1.0, 1.5, or 2.0 mg/mL). The particle size was measured by Nanosizer. Spray-dried powders (SDP) were prepared by addition of Aerosil 200 into suspensions of NC. IND was assayed by HPLC. Free IND was determined using an Ultrafree. NC-SPD were examined under SEM. The particle sizes of all formulations are in the sub-300 nm range and are IND-associated, with drug recovery close to 100%. After 1 month, the formulations with highest drug content (2.0 mg/mL) showed a decline of total quantity of IND. After spray-drying, IND recovery for SDP presented values above 100%, indicating that the drug was concentrated from loss of mass during the process. To verify the relationship of oil phase with this loss of mass, similar NC (IND 1.5 mg/mL) prepared with Miglyol 810 (MI) were spray-dried, and SEM analysis showed nanostructures adsorbed onto SiO2. Similar nano-structures were not visualized for NC samples prepared with BnB. A swelling experiment showed the complete dissolution of both polymer by the BnB, whereas for MI the polymer masses remained unchanged. In conclusion, BnB is a solvent for PLA and P epsilonC and this ester is entrained during spray-drying. Despite the use of BnB in formulations of NC, PLA, or P epsilonC, colloidal suspensions prepared with BnB could be micelles instead of nanocapsules.
