First-order Release Model Research Articles

Multiunit floating drug delivery system of acyclovir: development, characterization and in vitro-in vivo evaluation of spray-dried hollow microspheres

Abstract Acyclovir, anti-herpes virus drug, was loaded in hollow microspheres to improve bioavailability and patient compliance by prolonging the residence time in the gastrointestinal tract. The hollow microspheres of acyclovir were prepared by spray-drying method using ethyl cellulose as a drug-controlled release polymer. We found that the selected process parameters of spray-drying method like inlet temperature, outlet temperature, spray flow rate and vacuum pressure can give rise to hollow microspheres with good yields of production, high drug content and buoyancy, narrow size distribution and good encapsulation efficiency. The size of the microspheres prepared from different ratios of acyclovir and ethyl cellulose was 1.1-2.7 μm. When the drug:polymer ratio was increased, the size and percent drug content increased. The hollow microspheres having higher polymer concentrations were less buoyant than those with lower polymer concentrations. The formulation HSF1 showed the highest buoyancy of 94.18 ± 4.4 %. Dissolution profiles indicate that when drug:polymer ratio increased from 1:2 to 1:6, a decrease in release rate was observed. The highest correlation coefficient was obtained in first-order release model as compared to zero-order followed by Higuchi model. From the Higuchi plot it was found that drug release from the microspheres was diffusion type. The ‘n’ values from Korsmeyer-peppas model indicated that all three formulations follow Fickian diffusion controlled release. The AUC values for oral administration of selected formulation and conventional tablet (Zovirax) clearly indicated two- to three-fold improvement in the bioavailability of acyclovir from prepared formulation when compared to conventional commercial tablet.

Effect of cations on the microstructure and in-vitro drug release of κ- and ι-carrageenan liquid and semi-solid aqueous dispersions

OBJECTIVES The main objective of this study was to determine the effect of potassium and calcium ions on the microstructure and release dynamics of kappa (κ) and iota (ι) carrageenan. The microstructure of the dispersions was imaged using a cryogenic scanning electron microscope. Franz-cell diffusion apparatus was used to determine the release kinetics of a model hydrophilic drug, sodium fluorescein, incorporated in selected polymer dispersions. Release profiles were analysed using Higuchi, Korsmeyer-Peppas and dual first-order models. Cryogenic scanning electron microscope images showed that κ-carrageenan forms hexagonal structures, whereas ι-carrageenan forms rectangular pores at low cation concentrations. In-vitro release studies showed sustained release profiles for all carrageenan systems; however the model drug, fluorescein, diffusion from ι-carrageenan with 0.06% w/v calcium was significantly higher than other ι-carrageenan systems. This may be attributed to improved tortuosity of this system. However further increase in cation concentration led to a reduction in fluorescein release from the matrices. The dual first-order release model illustrated two distinct release rates, an initial rapid release followed by a slow diffusion of fluorescein from the carrageenan matrices. The observed microstructural differences may account for the well known variation in mechanical properties of κ- and ι-carrageenan gels. The dual first order release model adds a new tool in the elucidation of release mechanisms from polymer matrices, where parallel processes contribute to drug release.

Development of a Respirable, Sustained Release Microcarrier for 5-Fluorouracil I: In Vitro Assessment of Liposomes, Microspheres, and Lipid Coated Nanoparticles

The release rate of 5-fluorouracil (5-FU) from liposomes, microspheres, and lipid-coated nanoparticles (LNPs) was determined by microdialysis to investigate their use as a respirable delivery system for adjuvant (postsurgery) therapy of lung cancer. 5-FU was incorporated into liposomes using thin film hydration and into microspheres and LNPs by spray drying. Primary particle size distributions were measured by dynamic light scattering. Liposomes released 5-FU in 4-10 h (k(1) = 0.44-2.31/h, first-order release model). Extruded vesicles with diameters less than one micron released 5-FU more quickly than nonextruded vesicles. With poly-(lactide) (PLA) and Poly-(lactide-co-glycolide) (PLGA) microspheres, slower release rates were observed (k(1) = 0.067-0.202/h). Increasing the lactide:glycolide ratio (50:50-100:0) resulted in a progressive decrease in the release rate of 5-FU. poly-(lactide-co-caprolactone) (PLCL) microspheres released 5-FU more rapidly compared to PLGA systems (k(1) = 0.254-0.259/h). LNPs formulated with polymeric core excipients had lower release rates compared to monomeric excipients (k(1) = 0.043-0.105/h vs. k(1) = 0.192-0.345/h). Changing the lipid chain length of the shell lipid components had a relatively minor effect (k(1) = 0.043-0.129/h). Overall, these systems yielded a wide range of delivery durations that may be suitable for use as an inhalation delivery system for adjuvant therapy of lung cancer.

Measurement of drug release from microcarriers by microdialysis

The purpose of this study was to examine the feasibility of the microdialysis sampling technique as a method to precisely and conveniently measure drug release from microcarrier systems such as liposomes and microspheres. Release of 5-fluorouracil (5-FU) from liposomes and microspheres was evaluated in vitro using microdialysis. Retrodialysis calibration using 5-chlorouracil (5-CU) was performed in conjunction with on-line HPLC analysis. At a microdialysis perfusate flow rate of 0.5 μL/min, concurrent 5-FU gain and 5-CU loss ranged from 72% to 75%, while concurrent 5-FU loss and 5-CU ranged from 69% to 71%. After calibration, simultaneous 5-FU release profiles were obtained by continuous microdialysis and discrete equilibrium dialysis sampling using a side-by-side diffusion apparatus. Release rates were characterized by a first-order release model. The release rate constants for a representative liposomal formulation were 0.30 and 1.85/h by microdialysis in the acceptor and donor compartments, respectively, and 0.39/h by equilibrium dialysis in the acceptor compartment. The calculated release rate constant determined by equilibrium dialysis in the donor compartment (1.98/h) agrees with that determined by microdialysis (1.85/h) when the resistance of the equilibrium dialysis membrane with associated first-order rate constant of transfer of 0.42/h is taken into account. Release profiles of 5-FU from a number of different liposome and microsphere formulations were determined. The results indicate that a convenient and reproducible characterization of drug release from various liposome and microsphere formulations is readily obtainable by microdialysis. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association.