Preparation, characterization, and biodistribution of letrozole loaded PLGA nanoparticles in Ehrlich Ascites tumor bearing mice.

Letrozole (LTZ) incorporated PLGA nanoparticles were prepared by solvent displacement technique and characterized by transmission electron microscopy, poly-dispersity index and zeta potential measurement. Radiolabeling of free LTZ and LTZ-loaded PLGA NPs was performed with technetium-99m with high labeling efficiency. The labeled complex showed good in vitro stability as verified by DTPA challenge test. The labeled complexes also showed significant in vivo stability when incubated in rat serum for 24 h. Biodistribution studies of (99m)Tc-labeled complexes were performed after intravenous administration in normal mice and Ehrlich Ascites tumor bearing mice. Compared to free LTZ, LTZ-loaded PLGA NPs exhibited significantly lower uptake by the organs of RES. The tumor concentration of LTZ-loaded PLGA NPs was 4.65 times higher than that of free LTZ at 4 h post-injection. This study indicates the capability of PLGA nanopartcles in enhancing the tumor uptake of letrozole.

Multiunit floating drug delivery system of rosiglitazone maleate: development, characterization, statistical optimization of drug release and in vivo evaluation.

A multiunit floating drug delivery system of rosiglitazone maleate has been developed by encapsulating the drug into Eudragit RS100 through nonaqueous emulsification/solvent evaporation method. The in vitro performances of microspheres were evaluated by yield (%), particle size analysis, drug entrapment efficiency, in vitro floating behavior, surface topography, drug-polymer compatibility, crystallinity of the drug in the microspheres, and drug release studies. In vitro release was optimized by a {3, 3} simplex lattice mixture design to achieve predetermined target release. The in vivo performance of the optimized formulation was evaluated in streptozotocin-induced diabetic rats. The results showed that floating microspheres could be successfully prepared with good yields (69-75%), high entrapment (78-97%), narrow size distribution, and desired target release with the help of statistical design of experiments from very small number of formulations. In vivo evaluation in albino rats suggested that floating microspheres of rosiglitazone could be a promising approach for better glycemic control.

Development and validation of RP-HPLC method to determine letrozole in different pharmaceutical formulations and its application to studies of drug release from nanoparticles.

This study describes development and subsequent validation of a reversed phase high performance liquid chromatographic (RP-HPLC) method for estimation of letrozole, a new aromatase inhibitor, in raw material, pharmaceutical formulations like tablets and nanoparticles and in release medium. The chromatographic system consisted of a FinePak C, column, an isocratic mobile phase composed of deionized water, acetonitrile and methanol (50:30:20 v/v/v) and UV detection at 240 nm. Letrozole was eluted at 9.8 min with no interfering peak of excipients used for the preparation of dosage forms. The method was linear over the range from 1 to 50 microg/mL in raw drug (R2 = 0.9999). The intra-day and inter-day precision values were in the range of 0.122-0.277%. Limit of detection and limit of quantitation were 0.207 microg/mL and 0.627 microg/mL, respectively. Results were validated statistically according to ICH guidelines in both tablets and nanoparticles. Validation of the method yielded good results concerning range, linearity, precision and accuracy. The method was successfully applied in drug release studies from nanoparticles. The release kinetics was found to be fitted into the Higuchi model.

Effect of different formulation variables on some particle characteristics of poly (DL-lactide-co-glycolide) nanoparticles.

This study investigates the effect of some formulation variables on particulate characteristics of poly (DL-lactide-co-glycolide) (PLGA) copolymer nanoparticles by applying 2(3) factorial design and response surface methodology (RSM). Nanoparticles were prepared by solvent displacement technique. Initially, appropriate formulation factors for elaboration of polymeric particles were selected by screening. A 2(3) full factorial design was employed to evaluate the influence of three formulation variables, polymer concentration (X(1)), dispersant concentration (X(2)) and phase volume ratio (X(3)) on the percentage of total particles at submicron range (Y(1)), mean diameter (Y(2)) and specific surface area (Y(3)) as particle characteristics. The results showed that all the three variables had significant influence on mean diameter of particles and amount of particles at submicron range. Simultaneous change of polymer concentration and dispersant concentration had significant effect on specific surface area of particles. Span value as an index of polydispersity indicated uniformity in particle size distribution.