Sunday, May 24, 2009

Mechanisms of Drug Release From Taste-Masking Fatty Acid Microspher

Mechanisms of Drug Release From Taste-Masking Fatty Acid Microspheres

Fatty acid microspheres based on stearic and palmitic acids are known to form effective taste-masking systems, although the mechanisms by which the drug is preferentially released in the lower gastrointestinal tract are not known. Microspheres were prepared by a spray chilling process. Using benzoic acid as a model drug and an alkaline dissolution medium, a faster drug release was observed in the mixed fatty acid formulation (50:50 stearic:palmitic acid (w/w)) compared to the single fatty acid component systems. Thermal and powder X-ray diffraction studies indicated a greater degree of acid soap formation for the mixed formulation in alkaline media compared to the single fatty acid systems. Particle size and porosity studies indicated a modest reduction in size for the mixed systems and an increase in porosity on immersion in the dissolution medium.

Powder X-ray diffraction patterns of drug loaded mixed stearic and palmitic acid micros-pheres (BA50SA50PAM, 106-63 ?m) before and after immersion in pH 8.0 Sorensens modified phosphate buffer for 4 hours.

It is proposed that the mixed fatty acid system form a mixed crystal system that in turn facilitates interaction with the dissolution medium, thereby leading to a greater propensity for acid soap formation. This, in turn, forms a permeable liquid crystalline phase through which the drug may diffuse. The role of dissolution of palmitic acid into the dissolution medium is also discussed as a secondary mechanism.

Qi S, Deutsch D, Craig D. An investigation into the mechanisms of drug release from taste-masking fatty acid microspheres. J Pharm Sci. 2008;97:3842-3854. Correspondence to Duncan Q.M. Craig, School of Chemical Sciences and Pharmacy, University of East Anglia, at or +44-1603-592023.

In Situ Gelling Hydrogels Incorporating Microparticles as Drug Delivery Carriers

(a) Effect of addition of microparticles on the gelling behavior of the hydrogel (polymer concentration: 25%). (b) Effect of particle size on the rheological property of the hydrogel incorporated with microparticles.

Aqueous solutions of blends of biodegradable triblock copolymers, composed of poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) with varied D,L-lactide to glycolide ratios, displayed thermosensitivity and formed a gel at body temperature. The gel window of the blend solutions could be tuned by varying the blending ratio between the two components. Furthermore, the storage modulus of the resultant hydrogel from the copolymer blends at body temperature was higher than that of each individual component.

Incorporation of poly(D,L-lactide) (PDLLA) microparticles (0.5-40% w/v) within the in situ gelling hydrogel did not change the sol-gel transition temperatures of the polymer solutions, while the mechanical strength of the resultant hydrogels was enhanced when the content of the microparticles was increased up to 30% and 40%. Incorporation of proteins into both the gel and microparticle components resulted in composites that controlled the kinetics of protein release. This system can be used to deliver two drugs with differing release kinetics.

Hou Q, Chau D, Pratoomsoot C, et al. In situ gelling hydrogels incorporating microparticles as drug delivery carriers for regenerative medicine. J Pharm Sci. 2008; 97:3972-3980. Correspondence to Felicity R.A.J. Rose, Centre for Biomolecular Sciences, The University of Nottingham, at

Chitosan-Coated Vesicles Encapsulating DNA

Zeta potential of the phospholipids DSPC (black), DPPC (gray), and DMPC (white) vesicles encapsulating calf thymus DNA with different amounts of DNA added to the vesicles.

Encapsulation of DNA of varying type and molecular weight in vesicles (dehydration-rehydration vesicles; DRV) prepared from zwitterionic phospholipids using the dehydration-rehydration method was determined to be in the range of 10-90%. Encapsulation was dependent on the amount of DNA added but not its molecular weight.

DRV were successfully coated with chitosan as evidenced by small angle neutron scattering studies and zeta potential measurements. The amount of chitosan coating the DRV [quantified by ultra violet (UV)/Vis spectroscopy] was dependent upon the starting concentration of chitosan and independent of the presence of DNA. Chitosan-coated DRV containing DNA exhibited improved size stability while empty uncoated vesicles were poorly stable. A coating of chitosan reduced the amount of DNA leaking from the vesicles.

Kudsiova L, Arafiena C, Lawrence MJ. Characterization of chitosan-coated vesicles encapsulating DNA suitable for gene delivery. J Pharm Sci. 2008; 97:3981-3997. Correspondence to L. Kudsiova, Department of Pharmacy, King's College London, at or +20-7848-4812.

Biodegradable Films Developed by Electrospray Deposition for Sustained Drug Delivery

Paclitaxel in vitro release profiles from PLGA films with different drug loadings (5%, 10%, 20%, and 30%). Each data point represents the average of n=3 samples, error bars represent standard deviations, and significance was determined by unpaired Student's t-test.

The objective of the study was to develop biodegradable films with controllable thickness for sustained release applications using a combination of electrospray deposition techniques. The model anticancer drug-paclitaxel was encapsulated inside PLGA films. The morphology observed by atomic force microscopy and scanning electron microscopy reveals that the film has a flat surface together with a dense structure.

X-ray photo-electron spectroscopy results show that some amount of paclitaxel is found on the surface layer of films. X-ray diffractometry analysis suggests that paclitaxel is in an amorphous form in the polymer matrix even for up to 30% drug loading. Differential scanning calorimetry study further proved that paclitaxel is in a solid solution state in polymer films. The in vitro release profile indicates that sustained release of paclitaxel from the films is for more than 85 days, without the tri-phasic release profile typical for PLGA films. The phase contrast images clearly suggest a slight decrease in the number of C6 glioma cells as the paclitaxel loading within the polymeric films is increased.

Xie J, Tan JC, Wang C. Biodegradable films developed by electrospray deposition for sustained drug delivery. J Pharm Sci. 2008;97:3109-3122. Correspondence to Chi-Hwa Wang, Department of Chemical and Biomolecular Engineering, National University of Singapore, at or +65-6516-5079.

Nano-Sized Assemblies for Docetaxel Formulation

Size and size distribution of micelles at different docetaxel loading levels.

An amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight methoxy poly(ethylene glycol) (PEG) (i.e., 2 kDa) to docetaxel (DTX) through an ester linkage. The PEG-DTX conjugate having a critical micelle concentration of 0.88 mg/mL was used to form nano-sized micelles, with mean diameters of less than 100 nm, for solubilization of free DTX.

The anti-cancer activity of the drug in the PEG-DTX micelle formulation was shown to be retained in three human cancer cell lines.

Intravenous administration of DTX in the PEG-DTX micelles revealed relatively rapid dissociation of the free drug from the formulation; however, a 1.8-fold higher DTX equivalent area under the plasma concentration-time curve (AUC) was obtained, in comparison to DTX administered as Taxotere.

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