acyclovir and betadex

In this study, two hydrophilic polymers hydroxypropyl methyl cellulose and beta-cyclodextrin (β-CD) are used to synthesize highly responsive and spongy polymeric matrices. Porous and stimulus-responsive polymeric network was developed to improve the solubility of acyclovir (ACV) at significant level. Grafting was successfully carried out by free radical polymerization technique. Spongy matrices were characterized by percentage entrapment efficiency, drug loading, solubility studies, FTIR, powder X-ray diffraction, TGA, DSC, XRD, SEM, swelling studies, and in vitro studies. Acute oral toxicity studies were conducted to determine the safety of oral administration of prepared HPMC-βCD-g-poly(AMPS) formulation. Porous and spongy structures were depicted in SEM images. Complex formation and thermal stability of constituents and drug (ACV) were analyzed by FTIR, TGA, and DSC spectra. XRD analysis revealed reduction in acyclovir crystallinity in spongy matrices. Particle size of optimized formulation was found in the range of 197 ± 2.55 nm. The momentous difference with reference product committed that drug solubility and release characteristics were markedly enhanced by the developed spongy matrices. Toxicity studies endorsed that developed spongy matrices were non-toxic and compatible to biological system. The efficient method of preparation, enhanced solubility, excellent physico-chemical characteristics, high dissolution, and non-toxic HPMC-βCD-g-poly(AMPS) spongy matrices may be a promising approach for oral delivery of poorly soluble drugs.

Topics: Acrylamides; Acyclovir; Administration, Oral; Alkanesulfonates; Animals; Antiviral Agents; beta-Cyclodextrins; Drug Evaluation, Preclinical; Hypromellose Derivatives; Male; Particle Size; Polymerization; Polymers; Rabbits; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

Objective of present work was to formulate polymeric microparticles of acyclovir using 0-cyclodextrin by solvent evaporation method and kneading technique. Four different ratios were fabricated in each case. Sodium lauryl sulfate (4% was utilized as intestinal permeation enhancer in this study. Prepared microparticles were characterized for micromeritic properties i.e., angle of repose, Hausner's ratio, Carr's index, bulk density and tapped density, entrapment efficiency, zeta size and zeta potential, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction, scanning electron microscopy, transmission electron microscopy, optical microscopy and permeability studies across chicken intestine. Kinetic models: zero order, first order, Higuchi and Korsmeyer Peppas were applied on release data. Based upon the results of entrapment efficiency (81.25% and 74.50%), product yield (92.50% and 85.50%), permeability (85.18% and 82.05%), x-ray diffraction (amorphous nature), and solubility etc., (1 : 2) drug-polymer ratio was declared the best. Moreover, solid dispersions (1 : 2) had shown promising results. A new potential approach for solubility, bioavailability and permeability enhancement of acyclovir and other BCS class IV drugs was successfully established.

Topics: Acyclovir; beta-Cyclodextrins; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Microscopy, Electron, Scanning; Particle Size; Permeability; Polymers; Solubility; Spectroscopy, Fourier Transform Infrared

We report the synthesis of an oligomeric prodrug of the antiviral agent Acyclovir (Acy) conjugated to β-cyclodextrin (β-CyD). The drug was selectively linked through a succinic spacer to one of the primary hydroxyl groups of β-CyD by ester linkage in a 1:1 molar ratio. The conjugate was purified by semipreparative reverse-phase chromatography and characterized by FAB mass spectrometry and NMR experiments. The release of Acy from the conjugate was evaluated both in acidic and in neutral conditions and in the presence of porcine liver esterase. In all cases we observed the release of both free Acy and Acy succinate (AcySucc) at differing rates as a function of the hydrolysis conditions. In the presence of esterase the release of free Acy was favoured over AcySucc, showing a release rate of 100% of Acy within 7 days.

Topics: Acyclovir; beta-Cyclodextrins; Chemical Phenomena; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Drug Liberation; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Time Factors

The design of β-cyclodextrin/multiwalled carbon nanotubes hybrid (β-CD-MWCNT) as nanoplatform for the entrapment and delivery of guanine based drugs is described here. The functionalized carbon nanomaterials have been characterized by XPS spectroscopy, electron microscopy (FEG-SEM and TEM), AFM, TGA, and FT-IR to achieve insights on structure, morphology and chemical composition. The drug binding abilities of nanocarrier towards the guanine (G) and Acyclovir (Acy) were proved by UV-vis and DSC experiments. Host-guest equilibrium association constants and drug loading have been evaluated for G/β-CD-MWCNT and Acy/β-CD-MWCNT complexes. The release studies showed a sustained delivery of Acy without initial burst effect confirming a strong interaction of drug with the nanoplatform sites. The preliminary antiviral data indicated that the Acyclovir loaded into the β-CD-MWCNT platform interferes with HSV-1 replication and the antireplicative effect was higher than the free drug.

Topics: Acyclovir; beta-Cyclodextrins; Click Chemistry; Guanine; Nanotubes, Carbon

Novel polymeric nanoparticles based on a beta-cyclodextrin-poly(4-acryloylmorpholine) mono-conjugate (beta-CD-PACM), a tadpole-shaped polymer in which the beta-CD ring is the hydrophilic head and the PACM chain the amphiphilic tail, were prepared by the solvent injection technique. Acyclovir-loaded nanoparticles were prepared from inclusion complexes of Acyclovir with beta-CD-PACM. Both unloaded and drug-loaded nanoparticles were characterized in terms of particle size distribution, morphology, zeta potential, drug loading and in vitro drug release rate. The antiviral activity of Acyclovir loaded into beta-CD-PACM nanoparticles against two clinical isolates of HSV-1 was evaluated and found to be remarkably superior compared with that of both the free drug and a soluble beta-CD-PACM complex reported in a previous paper. Fluorescent nanoparticles loaded with coumarin 6 were also prepared in order to investigate the nanoparticle cell uptake by confocal laser microscopy. It was found that the nanoparticles are internalized in cells and locate in the perinuclear compartment.

Topics: Acrylamides; Acyclovir; Animals; Antiviral Agents; beta-Cyclodextrins; Cell Membrane Permeability; Cell Survival; Chlorocebus aethiops; Coumarins; Drug Carriers; Herpesvirus 1, Human; Morpholines; Nanoparticles; Particle Size; Polymers; Thiazoles; Vero Cells

Baseline separation of some new acyclic nucleosides which are potential antiviral agents was achieved using cyclodextrin capillary zone electrophoresis (CD-CZE). A method for the enantiomeric resolution of these compounds and determination of their enantiomeric purity was developed using anionic CDs (highly sulfated-CD or highly S-CD) as chiral selectors and capillaries, which were dynamically coated with polyethylene oxide (PEO). Operational parameters including (i) the nature and concentration of the chiral selectors, (ii) organic modifiers, (iii) temperature, and (iv) applied voltage were investigated. The use of charged CDs provides (i) a supplementary driving force for the compounds in a running buffer and (ii) enantiomeric resolution by inclusion of compounds in the CD cavity. The highly S-CD was found to be the most effective complexing agent and allowed good enantiomeric resolution. The complete resolution of five nucleoside analogs was obtained using 25 mM phosphate buffer, pH 2.5, containing either highly S-alpha-CD, S-beta-CD or S-gamma-CD at 30 degrees C with an applied field of 0.30 kV/cm. The apparent association constants of the inclusion complexes were calculated. The enantiomer migration order for the molecules investigated was determined and the detection limit of enantiomeric impurities was found to vary between 0.34 to 3.56 ng.mL(-1) for the first enantiomer.

Topics: Acyclovir; Anti-HIV Agents; beta-Cyclodextrins; Cyclodextrins; Electrophoresis, Capillary; Nucleosides; Stavudine; Stereoisomerism; Sulfates

Acyclovir has absorption problems, because of its low solubility and/or its saturable absorption mechanism, that take place in the small intestine in a passive, variable, and incomplete manner. The oral bioavailability of acyclovir is thereby affected and reaches only 15-30%. The purpose of this study was to investigate the possibility of increasing the oral availability of acyclovir by forming inclusion complexes of acyclovir with beta-cyclodextrin. Acyclovir, its complex (1:1) with beta-cyclodextrin (acyclovir-beta-cyclodextrin complex), and a 50:50 mixture of acyclovir and the inclusion complex (acyclovir/complex mixture) as an aqueous suspension were administered intraintestinally to male Sprague-Dawley rats in doses equivalent to an acyclovir dose of 75 mg/kg. Sequential samples of plasma were taken by microdialysis. The samples were analyzed by high-performance liquid chromatography with ultraviolet detection. Plasma concentration versus time curves show that the complex and the mixture of acyclovir/complex have a higher bioavailability and a pharmacokinetic profile than that of the drug itself.

Topics: Acyclovir; Animals; Area Under Curve; beta-Cyclodextrins; Biological Availability; Chemistry, Pharmaceutical; Cyclodextrins; Male; Rats; Rats, Sprague-Dawley