Drug Delivery Letters - Volume 2, Issue 4, 2012

The purpose of this study was to develop a solid nanoemulsion preconcentrate (NanOsorb) for poorly watersoluble drug sertraline (SRT). The liquid SNEDDS consisted of LabrafilM 2125 CS and Maisine 35-1 in 1:1 ratio as oil phase, Tween 80 as surfactant, Lauroglycol 90 as co-surfactant and active constituent sertraline free base. SRT free base, rather than commercially available hydrochloride salts (SRT.HCl) was used due to its much higher solubility in lipidic solvents. The NanOsorb formulation was prepared by adsorbing the liquid SNEDDS on different solid adsorbents. Reconstitution properties of both liquid and solid formulation demonstrate insignificant difference (p > 0.05) in the globule size. External morphology and physical state of sertraline in NanOsorb formulation were examined by TEM, DSC, and X-ray powder diffraction. In vitro release profile of NanOsorb was found to be significant (p < 0.001) in comparison to the plane SRT in pH 1.2, 4.5 and 6.8 buffers. Formulation was subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and was found to be stable. No significant variations were observed in the formulation over a period of 3 months at accelerated conditions. Results deduced that NanOsorb formulation may provide an improvement in dissolution profile of poorly water-soluble drugs in the form of solid dosage form.

Polysaccharides have attractive advantages for using in the field of pharmaceutics. In most cases, they are non toxic, biocompatible and plentiful. The presence of hydroxyl groups (always) and carboxylic acid groups (sometimes) permits crosslinking of the chains and obtaining hydrogels. These hydrogels present interesting swelling and mechanical properties. They have the capacity to entrap active compounds such as drugs and release them through modifications of the solvation conditions vias pH or ionic strength changes. This review deals with polysaccharide hydrogels obtained by the formation of covalent bounds between polymeric chains. We have focused our attention on systems with an anionic character. These charges are due to the presence of acidic functions on the polysaccharide backbone or are brought by the crosslinking agent. The anionic character dependents on the ionic strength and pH. We discuss the synthesis of these hydrogels. After a short presentation of a few polysaccharides, we describe the different crosslinking agents and their action mode. Applications in drug delivery are discussed along.

In order to achieve high bioactivity, low systemic side effects and prevention of high critical hypoglycaemic conditions of antidiabetic drugs in the treatment of diabetes mellitus, sustained and controlled delivery system is crucial. In this study, a three-dimensional (3-D) porous scaffold formulation was developed with the ability to release antidiabetic drugs in a controlled fashion. The gliclazide (GLZ), was successfully incorporated into prefabricated 3-D porous matrix chitosan scaffolds using a freeze-drying method. Porosity, swelling, water absorption and drug entrapment efficiency was increased after the addition of PEG 4000. The release kinetics of GLZ from two different (2% and 3%) chitosan scaffold formulations investigated showed sustained and controlled delivery of GLZ. The GLZ release is strongly dependent upon the physical and chemical properties of the chitosan and PEG 4000. Scaffold with 3% chitosan discharge GLZ rapidly with a high initial burst release while scaffold with 2% chitosan can extend the release of GLZ to longer than 2 weeks with a low initial burst release. Compared to chitosan alone, the PEG 4000 incorporated on a 3-D scaffold had significantly reduced the initial burst release. In-vivo antidiabetic tests of chitosan (2%)-PEG (1.5%) scaffold formulation demonstrated its ability to reduce blood sugar level for a prolonged duration (7 days). From this study, we concluded that, versatile carrier system i.e. porous scaffold formulation is effective for the delivery of GLZ for diabetes mellitus and maintain the concentration levels over a prolonged period of time, when compared against the free drug.

Gemcitabine hydrochloride (Gem HCL) is a drug of choice for the treatment of most cancers, as a single or in combination chemotherapy. However, its bioavailability is a major concern because of its short half life and highly hydrophilic nature. To tackle this problem work has been planned to prepare solid lipid nanoparticles (SLN) of Gem HCL and analyzed them for drug carrying capacity and efficacy in vitro. The Gem HCL loaded nanoparticles (SLN) were prepared by microemulsion technique and optimized for drug carrying capacity, entrapment efficiency, stability, and effect of Gem HCL loaded SLN by MTT assay on human lung carcinoma cell lines (NCI-H522). SLN dispersion showed particle diameter ranging from 170 nm to 296 nm. The scanning electron microscopy (SEM) further confirmed the particle size of SLN. All SLN batches showed drug entrapment efficiency ranging from 29.6% to 65.66%. The results of differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) showed that Gem HCL was dispersed in SLN in an amorphous state. The in vitro drug release study of the optimized formulation in phosphate buffer (pH 7.4) showed 56.73% of release of Gem HCL over a period of 24 hrs. Significant enhancement in the cytotoxic effect of Gem HCL loaded SLN, was noted compared to its liposome formulations. SLN mediated delivery can enhance the cytotoxic effects of Gem HCL compared to free drug and its liposomal formulation.

Penetration of healthy skin by drugs in solution is normally very limited due to the excellent barrier function of the stratum corneum (the most superficial layer of the skin). The goal of delivery system is to get optimal therapeutic management. But, it still remains a challenge in the field of pharmaceuticals for delivery of ionic species and some non ionic. This barrier can be overcome using iontophoresis: by applying an electrical potential (voltage) across the skin, drug ions become the charge carriers that convey the electrical current through the skin. Iontophoresis is being oppressed for the controlled delivery of drugs for systemic indications through synergistic approaches with other techniques like micro needle, electroporation and chemical approaches which may provide easier and more accurate delivery of macromolecules and poorly water soluble compounds. Iontophoresis may be particularly useful for the effective delivery of peptide, protein, drugs like cardiovascular agents, anaesthetics agents, anti-inflammatory agents etc. This article is an overview of the history of iontophoresis, mechanism, principles, factors influencing iontophoresis, synergistic approaches, patients related considerations, iontophoretic devices and their implementation and their application for various dermatological conditions.

5-Fluorouracil (5-FU) is a hydrophilic drug with short plasma half-life. The objective of the current study was to prepare and optimize 5-FU loaded chitosan nanoparticles (CNPs) for controlled release. The nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions. A 23 central composite design (CCD) was employed to study the influence of formulation variables - concentration of Chitosan (X1), the concentration of sodium tripolyphosphate (NaTPP) (X2) and volume of NaTPP (X3) on the cumulative percentage of drug release. The relationship between the dependent and independent variables was further elucidated using multiple linear regression analysis (MLRA) and Pareto chart. The results show that cumulative percent of 5-FU release was highest and lowest at high levels of X1, X2, and low level of X3, and high level of X1, and low levels of X2 and X3, respectively. The optimized nanoparticles were studied morphologically by transmission electron microscopy (TEM) which showed separated and non-aggregated nanoparticles with spherical shapes and smooth surfaces. The mean particle size, entrapment efficiency and loading capacity of the optimal CNPs were found to be 109.6±2.28 nm, 83.84±1.46%, and 37.76±3.41%, respectively. Nanoparticles revealed a fast release during the first hour followed by a more gradual drug release during a 24-h period following a non-Fickian diffusion process. Analysis of variance (ANOVA) was applied on cumulative percent of drug release to study the fitting and significance of model. The estimated model may be further utilized as response surface for cumulative percent of drug release from nanoparticles. The 5-FU loaded CNPs optimized using CCD showed good entrapment efficiency and controlled release as well as can reduce dosing frequency, decrease side effects and improve patient compliance.

The aim of proposed research work was to develop a bioadhesive sustained release matrix tablets of zolmitriptan for treatment of migrane. Compression coating technology was used for preparing the tablets that released the drug unidirectionally. Drug loaded core tablets were prepared with mucoadhesive and sustained release polymers like Noveon AA1 Polycarbophil and hydroxypropyl methylcellulose (HPMC K4M) while unloaded coat tablets, that covered the three surfaces of the core tablet, were prepared using ethyl cellulose and Compritol ATO 888. A two factor, three level, face centred, central composite design (CCD) was used to optimize amount of Noveon AA1 and amount of HPMC so as to get required mucoadhesion and rate of drug release. Higher levels of HPMC K4M in the experimental design batches exhibited higher in vitro drug release in the initial hour while the NoveonAA1 levels could be related to increase in mucoadhesive strength. Overlay plot comprising a region that satisfied the constraints for all the selected attributes was generated. Formulation containing 10% w/w of Noveon AA1 and 10% w/w of HPMC K4M was found to be optimum. Checkpoint batches were also prepared to validate the evolved mathematical models. Korsmeyer-Peppas release kinetic model best fitted the optimized batch release profile which showed anomalous diffusion mechanism. The In Vitro drug release could be correlated with the Ex vivo drug permeation. It can be concluded that buccal route can be one of the alternatives available for administration of zolmitriptan.