Drug Delivery Letters - Volume 4, Issue 2, 2014

Albendazole, an anthelmintic drug belonging to BCS class II, has poor bioavailability. Bioavailability is dissolution rate dependent and hence needs novel approach for enhancement of bioavailability. The aim of the study was to develop nanosuspension of albendazole by using various techniques like nanoprecipitation, emulsion template and sonication. Nanosuspensions were prepared using polyvinylpyrrolidone K30 as a stabilizer and Tween 80 as a surfactant. Average particle size, zeta potential, particle size distribution, pH, viscosity, photomicrography, sedimentation, redispersibility and % drug content were determined to characterize prepared nanosuspensions. In vitro release study was performed in 0.1N HCl using cellophane membrane and compared with marketed product. Residual solvent determination was carried out by gas chromatography for nanosuspensions prepared by nanoprecipitation and emulsion template techniques. All the results obtained for characterization were satisfactory. The prepared nanosuspensions showed particle size 673±9.18 nm to 893±21.6 nm, zeta potential -8.70±0.5mV to -8.96±0.8, polydispersity index 0.204±0.04 to 0.644±0.07. In vitro release study of the nanosuspensions showed 33.80% to 42.92% drug release in first hour which was higher than the marketed suspension (16.19% release in first hour). The optimized nanosuspensions showed up to 97.05 % drug release within 6-8 hours while marketed product showed up to 91.03% drug release within 10 hours.

For many years, improvements have been made in certain attempts for liposomal stability, by several methods, including preparing more stable bi-layers, coating their surface with protecting polymers, and modifying charge. These methods on subjecting to certain changes have led to a novel type of liposomes called proliposomes. Dry, free-flowing particles with a dispersed system that can form a liposomal suspension immediately when in contact with water called Proliposomes. These Proliposomes are as good as or even better than conventional liposomes. Because of their solid properties, the physical stability of liposomes can also be improved upon without influencing their intrinsic characteristics and show more advantages in promoting drug absorption. Therefore, proliposomes would be a potential vehicle to help improve the oral absorption of hydrophobic drugs. The focus of this review is to bring out different aspects related to liposomes, Proliposomes preparation, characterization, entrapment efficiency, in vitro drug release, applications and merits.

The present research work was aimed to design the transdermal delivery system of naproxen using Aloe vera as aqueous gel base. Aloe vera would able to potentiate the anti-inflammatory effect and also act as penetration enhancer. Carbopol 934 was used as a gelling agent. The prepared gel was assessed for pH, permeation parameters, drug content, skin irritation and in-vitro diffusion. Accelerated stability study was also carried out. In-vivo studies were performed to characterize the efficacy of the prepared naproxen-Aloe vera transgel (NAG). The pH of formulation was found to be 6.98. The values of permeation data for flux, permeability coefficient and enhancement ratio were obtained as 0.00907 µg cm-2 h-1, 0.00453 cm h-1 and 5.96 respectively. The viscosity was found as 610 cps for NAG. The drug release kinetics followed Higuchi model. Stability study has proved the integrity of the formulation. No skin irritation was observed in Wistar albino rats. Anti-inflammatory assessment in Wistar rats showed significant effect in paw-volume reduction at p<0.05 in less than one hour for NAG compared to that of plain Aloe gel and commercial naproxen gel (CNG). The prepared naproxen-Aloe gel (NAG) could able to show better anti-inflammatory activity compared to the CNG. This could be attributed by synergistic effect of Aloe.

Cancer is one of the major causes of the death worldwide and its prevalence is expected to reach about 27 million by 2050 due to aging, adoption of cancer causing behaviours and limitations of cancer treatment. The major therapeutic approach for the treatment of cancer is chemotherapy but most chemotherapeutic agents experience some limitations including poor aqueous solubility, systemic toxicities and drug resistance. The better alternative seems to be functional foods, which are devoid of systemic toxicities at the therapeutic doses. Curcumin is one such functional food isolated from dried rhizome of turmeric and reported to inhibit proliferation, invasion, angiogenesis and metastasis of various cancer cells. However, the clinical usefulness of curcumin in the treatment of cancer is limited due to limited solubility in water, hydrolytic degradation in alkaline pH, metabolism via glucuronidation and sulfation and reduced oral bioavailability. Various approaches have been reported to overcome the limitation of conventional curcumin. Of all, nanotechnology is the most recent and showing encouraging results. This review highlighted the nanoparticulate drug delivery systems that have been developed to overcome the limitations of curcumin in the treatment of cancer. However, about 60-70% of an oral dose of curcumin gets eliminated as its metabolites and there were no reports of nanoparticulate drug delivery system that overcome the metabolism of curcumin. Bio-enhancer such as piperine, quercetin and silibinin prevent/minimize the metabolism of curcumin and utilizing these bio-enhancers along with curcumin as a dual drug loaded nanoparticles are hypothesized to overcome all the limitations of curcumin.

Cinnarizine pediatric preparation is extemporaneously prepared from adult tablets or capsules that are unstable in liquid dosage form. The aim of this work is to develop cinnarizine oral pediatric formulation with improved stability and organoleptic properties as well as to achieve ease of administration. For this purpose, cinnarizine-loaded microspheres of chitosan cross-linked with tripolyphosphate anion were prepared. A full 23 factorial design of experiment approach was employed to evaluate the individual and the combined effect of the independent variables namely, concentration of each of chitosan (XA), tripolyphosphate (XB), and that of cinnarizine (XC) on the different responses namely drug entrapment efficiency, drug content, percentage yield and drug release rate for the prepared microspheres. Statistical analysis through response-surface methodology as well as contour plots was assessed. The optimized microspheres (formula 4) showed 93.6±3.3 % percentage yield, 74.3±0.8 mg drug loading, 74.3±0.8 % encapsulation efficiency and 0.19 µm particle size. Hence, it was subjected to stability study of cinnarizine in the dry microspheres immediately thereafter preparation through transmission electron microscope, x-ray diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry. The microspheres were further dispensed in the prepared syrup and the suspension was subjected to accelerated stability study, as mentioned in the International Conference on Harmonization (ICH) guidelines. Subsequently, oral bioavailability study of (formula 4) microspheres was conducted on rats and compared with aqueous suspension of the plain drug. Formula 4 complied successfully with ICH guidelines and experienced enhanced extent of bioavailability with long mean residence time (MRT).

Synthetic DNA molecules of 10-23 deoxyribozymes (Dz) are known to be efficient and site-specific agents for the RNA cleavage in a catalytic manner. To provide the penetration of Dz into cells, we have proposed the new delivery system for deoxyribozymes in the form of TiO2•PL-Dz nanocomposite. These nanocomposites consist of catalytically active Dz molecules noncovalently immobilized through the polylysine linker to TiO2 nanoparticles, which provide the penetration of Dz into cells. Deoxyribozymes in the prepared TiO2•PL-Dz nanocomposites were shown to retain their ability to cleave RNA targets albeit at a slower rate but with the same site-specificity and similar efficiency as free Dz. Unlike free Dz, the proposed TiO2•PL-Dz nanocomposites penetrate into cells without auxiliary actions.

Minoxidil loaded nanosponges (NS) based hydrogel system was developed for topical application on to the scalp in order to avoid the disadvantages associated with the Minoxidil topical solution. The objective of this work was to formulate, characterize and evaluate hydrogel system bearing minoxidil loaded nanosponges. Nanosponges were developed using solvent evaporation method by reacting β-cyclodextrin with a cross linking agent such as diphenyl carbonate that forms a porous nano-size structure. The drug was loaded in the nanosponges using solid dispersion method. The NS and NS minoxidil complexes were characterized by differential scanning calorimetry and scanning electron microscope. The drug-loaded nanosponges were incorporated in the hydrogel formulations and were evaluated for appearance, homogeneity, gelling, pH, viscosity, spreadability and drug content. The in-vitro drug release was carried out in phosphate buffer pH 6.8 for the drug loaded nanosponges hydrogel formulations HF1, HF2, HF3 and HF4 and the drug release was found to be 68.5±72, 61.27±0.83,56.36±0.55 and 52.18±1.7 respectively, over a period of 6 hours.

With the development of nanotechnology different biological nanomaterials have been developed, out of these, Carbon Nanotubes (CNTs) have attracted attention of various scientists as a carrier for the delivery of therapeutic agents. CNTs are third allotropic form of carbon-fullerenes which consist of graphite sheet rolled up into a cylindrical tube. They have nanometer scale diameter with high aspect ratio. CNTs exist in two forms, single-wall (SWCNTs) and multiwall (MWCNTs) depending on the number of graphene layer they are surrounded with as well as to the method of synthesis. Techniques have been developed to produce nanotubes in sizeable quantities, including Electrical arc discharge, Laser ablation, Chemical vapor deposition, Gas phase catalytic processes, as they tend to strip carbon atoms off from the carbon bearing compounds. Various techniques are available for the evaluation of CNTs which mainly involve the estimation of purity, functionalization and structure variations. Presence of impurities in the CNTs makes them vulnerable to be used as carrier in drug delivery hence CNTs need to undergo purification. To integrate into biological system CNTs can be loaded with active molecules by forming stable covalent bonds or supramolecular assemblies based on non-covalent interactions. Functionalized CNTs have been remarkably shown to exert their potential benefits in drug delivery, drug targeting and various other fields such as diagnostic, tissue regeneration. This review attempts to highlight all aspects of CNTs such as their structure, characterization, synthesis and purification, functionalization, bio-compatible applications in the clinical science and toxicity related issues due to CNTs.

Quetiapine fumarate (QF) is an atypical antipsychotic, undergoing extensive first pass metabolism and hence shows lower bioavailability orally. Solid Lipid Nanoparticles (SLNs) of QF were developed using lipid dynasan 114 and surfactant poloxamer 188 and 407 by double microemulsion-solvent evaporation technique. The aim of this study was to develop and evaluate SLNs of QF for enhancement of bioavailability via oral route. A Box-Behnken design has been applied to study the effect of independent variables i.e. lipid concentration, surfactant concentration and homogenization time on dependent variables i.e. particle size and entrapment efficiency. Optimized SLNs were evaluated for morphological characteristics using scanning electron microscopy, and were further evaluated for entrapment efficiency, drug content, fourier transform infrared spectroscopy, differential scanning calorimetry and In vitro drug release study. The formulation was also subjected to In vivo pharmacokinetic study using a rat model for determination of bioavailability. In vivo study suggested increase in bioavailability of QF SLNs (up to 10 fold increase in Area under curve) as compared to pure drug suspension following oral administration. The enhanced relative bioavailability by the SLNs formulation might be attributed to avoidance of first-pass hepatic metabolism by intestinal lymphatic transport, direct uptake of nanoparticles through the GI tract, increased permeability by surfactants, and decreased degradation of drug. The results suggest that QF SLNs can be used as an approach for enhancement of bioavailability of QF via oral route.