Malay K. Das

Furosemide-loaded Alginate Microspheres Prepared by Ionic Cross-linking Technique: Morphology and Release Characteristics.

Furosemide-loaded alginate microspheres were prepared by the ionic cross-linking technique using CaCl2, Al2(SO4)3 and BaCl2. The process induced the formation of microspheres with the incorporation efficiency of 65% to 93%. The effect of sodium alginate concentration, cross-linking agents and drying conditions was evaluated with respect to entrapment efficiency, particle size, surface characteristics and in vitro release behaviors. Infrared spectroscopic study confirmed the absence of any drug-polymer interaction. Differential scanning calorimetric analysis revealed that the drug was molecularly dispersed in the alginate microspheres matrices showing rough surface, which was confirmed by scanning electron microscopy study. The mean particle size and entrapment efficiency were found to be varied by changing various formulation parameters. The in vitro release profile could be altered significantly by changing various formulation parameters to give a sustained release of drug from the microspheres. The kinetic modeling of the release data indicate that furosemide release from the alginate microspheres follow anomalous transport mechanism after an initial lag period when the drug release mechanism was found to be fickian diffusion controlled.

Microencapsulation of zidovudine by double emulsion solvent diffusion technique using ethylcellulose

Zidovudine-ethylcellulose microspheres were prepared by water-in-oil-in-oil double emulsion solvent diffusion method. Spherical free flowing microspheres having an entrapment efficiency of 32-54% were obtained. The effect of polymer-drug ratio, surfactant concentration for secondary emulsification process, volume of processing medium and stirring speed of secondary emulsification process was evaluated with respect to entrapment efficiency and in vitro drug release behaviors. Infrared spectroscopy and differential scanning calorimetric analysis confirmed the absence of any drug polymer interaction. The in vitro release profile could be altered significantly by changing various processing and formulation parameters to give a controlled release of drug from the microspheres. The in vitro release profiles from microspheres of different polymer-drug ratios were applied on various kinetic models. The best fit with the highest correlation coefficient was observed in higuchi model, indicating diffusion-controlled principle. The n value varies between 0.23-0.54 obtained from korsemeyer-peppas model confirmed that the mechanism of drug release was diffusion controlled.

Preparation and in vitro characterization of diltiazem hydrochloride loaded alginate microspheres

The main objective of the present study was to improve bioavailability of diltiazem hydrochloride and decrease the frequency of dosage form administration by increasing the encapsulation efficiency of the drug, residence time of the dosage form at the site of absorption and sustained release of the drug from the delivery system. Alginate microspheres containing diltiazem hydrochloride were prepared by the emulsification-internal gelation method by using barium carbonate as a cross-linking agent with improved encapsulation efficiency. The effect of various factors (concentration of alginate and barium chloride) on the drug loading efficiency and in vitro release were investigated. Fourier transform infrared spectroscopy (FT-IR) analysis confirmed the absence of any drug polymer interaction. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) pattern showed that the crystallinity of the drug was decreased in the dosage forms. The in vitro drug release mechanism was non-Fickian type controlled by swelling and relaxation of polymer. The stability studies of drug-loaded microspheres showed that the drug was stable at different storage conditions.

Transdermal delivery of trazodone hydrochloride from acrylic films prepared from aqueous latex

Trazodone hydrochloride has not been previously investigated and reported for potential administration through transdermal route. Therefore, the present investigation was carried out to study the effect of polymeric composition, drug content and plasticizer on the permeation of trazodone hydrochloride across the mouse epidermis for the development of transdermal therapeutic system. The pseudolatex films with different combination of polymers, plasticizer and drug were prepared from aqueous colloidal polymer dispersions. The polymers used were Eudragit RL100 and RS100. Triethylcitrate was used as plasticizer. The in vitro release and skin permeation through mouse epidermis from the prepared films were studied using Keshary-Chien diffusion cell. The in vitro drug release increased with increasing amount of Eudragit RL100 in the film. It was observed that the maximum skin permeability was attained at a loading dose of 10% w/w in the film. The in vitro flux decreased gradually at higher concentration up to 13% w/w. The present study has demonstrated the potential of the fabricated pseudolatex transdermal films for sustained release of trazodone hydrochloride. The concentration of triethylcitrate in the film markedly affected the skin permeation properties of trazodone hydrochloride.

Effect of different terpene-containing essential oils on percutaneous absorption of trazodone hydrochloride through mouse epidermis.

The aim of our study was to investigate the enhancing effect of several essential oils in the percutaneous absorption of trazodone hydrochloride (TZN). For this purpose, fennel oil, eucalyptus oil, citronella oil, and mentha oil were applied on the skin membrane in three different ways: included in the transdermal device, as a pretreatment, or both. To investigate the effect of penetration enhancers used in this study on the percutaneous absorption of TZN through mouse epidermis, Keshary-Chien diffusion cells were employed. The receptor phase was constantly stirring saline phosphate buffer of pH 7.4 at 37 ± 1°C. Results showed that pretreatment of skin with essential oils increases the flux values of TZN compared with the values obtained when the same essential oils were included in the transdermal devices. The percutaneous penetration flux for TZN was increased with skin pretreatment by 10% essential oils in the following order: fennel oil > eucalyptus oil > citronella oil > mentha oil. The amount of TZN retained in the skin after pretreatment with essential oils was found to be very similar in all cases and much higher than in the experiments without skin pretreatment.

GUAR GUM: PRESENT STATUS AND APPLICATIONS

Naturally occurring excipients are currently getting prime importance among which the polysaccharides occupy a special positi on because of their easy availability, non - toxic, eco - frien d ly and biodegradable nature. The objecti ve of this review was to explore the excipient profile of Guar gum which is obtained from Cyamopsis tetragonolobus (Linn. Leguminosae). The chief constituent of guar gum is a Gallactomannan which is composed of galactose and mannose in a ratio of 1:2 that provides the main physical phenomenon of gelling or thickening to this gum . The chemistry of this gallactomannan suggested the presence of multiple hydroxyl groups which are proved to be excellent for derivatiz ation by grafting or cross - linking with other polymers to create new chemically modified entity of desired properties. The native as well as guar gum derivatives are found to have therapeutic importance in certain physiological di sorders . Guar gum is used as suspending, emulsifying and stabilizing age nt in the conventional dosage forms. In tablet dosage form it is used as a potential binding and disintegrating agent. The swelling property of guar gum is used for controlling the drug release rate in the novel pharmaceutical dosage forms. By virtue of it s better thickening and stabilizing power accompanied by a sound safety profile, guar gum has acquired a wide acceptance in cosmetics and food industry .

Nano-ART and NeuroAIDS

Human immunodeficiency virus (HIV) is a neurotropic virus that enters the central nervous system (CNS) early in the course of infection. Although highly active antiretroviral therapy (HAART) has resulted in remarkable decline in the morbidity and mortality in AIDS patients, controlling HIV infections still remains a global health priority. HIV access to the CNS serves as the natural viral preserve because most antiretroviral (ARV) drugs possess inadequate or zero delivery across the brain barriers. The structure of the blood–brain barrier (BBB), the presence of efflux pumps, and the expression of metabolic enzymes pose hurdles for ARV drug-brain entry. Thus, development of target-specific, effective, safe, and controllable drug delivery approach is an important health priority for global elimination of AIDS progression. Nanoformulations can circumvent the BBB to improve CNS-directed drug delivery by affecting such pumps and enzymes. Alternatively, they can be optimized to affect their size, shape, and protein and lipid coatings to facilitate drug uptake, release, and ingress across the barrier. Improved drug delivery to the CNS would affect pharmacokinetic and drug biodistribution properties. This review focuses on how nanotechnology can serve to improve the delivery of antiretroviral medicines, termed NanoART, across the BBB and affect the biodistribution and clinical benefit for NeuroAIDS.

Curcumin-docetaxel co-loaded nanosuspension for enhanced anti-breast cancer activity

ABSTRACT Purpose: A curcumin-docetaxel co-loaded nanosuspension with increased anti-breast cancer activity was developed. Curcumin is a potential anticancer agent with p-glycoprotein (p-gp) inhibiting activity may be co-administered with docetaxel as a nanosuspension to enhance its anticancer effect by increasing the oral bioavailability and decreasing drug efflux. Methods: Nanosuspensions of curcumin and docetaxel were prepared by precipitation-homozenisation technique and evaluated for particle size, polydispersity, zeta potential and drug release. The in vitro MTT assay was conducted using MCF-7 for anti-breast cancer activity. The in vivo biodistribution by radiolabeling and tumor inhibition study was conducted in mice. Results: Homogenous nanosuspensions of 80 ± 20 nm were obtained with increased solubility. The drugs as nanosuspensions showed higher cytotoxicity on MCF-7 cell line compared to their suspensions due to the increased in vitro cellular uptake. Due to this increased solubility, sensitization of tumor cells and inhibition of p-gp the in-vivo results showed greater tumor inhibition rate of up to 70% in MCF-7 treated mice. Histopathological results showed higher apoptotic activity and reduced level of angiogenesis. Conclusions: The in vitro and in vivo study of the nanosuspensions has shown that Co-administration of Curcumin as a p-gp inhibitor with docetaxel may have the potential to increase the anti-breast cancer efficacy of both drugs.

PHYTOSOME: AN OVERVIEW

Novel drug delivery system aims to improve the shortcomings of conventional and traditional delivery systems. The novel delivery approach towards plant based drugs is gearing up and tremendous success have achieved in making phytoconstituent more bioavailable and stable. Polyphenolic phytoconstituent of flavonoid class have been known for centuries possessing diverse health giving properties but not extensively formulated to modern dosage forms due to problem in gastrointestinal absorption. A covalent complex of such phytoconstituent with phosphatidylcholine – the principle phospholipid of biological membrane makes them significantly bioavailable and stable. The complex such developed is a patented technology and given the name Phytosome. The phytosome technology markedly enhances the bioavailability of phytomedicine by making them soluble in GI fluid and enhancing lipid solubility. Important herbs including Milk thistle, Ginkgo biloba, Grape seed, Green tea, Hawthorn, Ginseng, etc. are currently available in phytosome form in the market. Phytosomal delivery is not restricted to flavonoids (polyphenol) class of phytoconstituents only, but any beneficial molecule possessing structural requirement for direct binding with phosphatidylcholine can be converted to phytosome, e.g. Andrographolide Phytosome, clarithromycin-phospholipid complex, glycerrhetinic acid-phospholipid complex, aceclophenac-phospholipid complex. Knowing the underlying objective, potentiality and diverse application of this novel phytosome technology, an attempt is accomplished to review the available literatures with research related to clinical aspect and formulation as well as success of this newer approach.

Progress in Brain Delivery of Anti-HIV Drugs -

Article history: Received on: 17/01/2015 Revised on: 22/04/2015 Accepted on: 17/06/2015 Available online: 27/07/2015 The HIV/AIDS pandemic is an increasing global burden with devastating health-related and socioeconomic effects. The widespread use of antiretroviral therapy has dramatically improved life quality and expectancy of infected individuals. But currently available drug regimens and dosage forms are not good enough to eradicate HIV. Suboptimal adherence, toxicity, drug resistance and viral reservoirs make the lifelong treatment of HIV infection challenging. Along with some other organs, highly vascularized and secured with blood-brain barrier (BBB), brain acts as a great reservoir for the HIV virus. But all the available drug delivery techniques are not capable of bypassing the BBB and deliver anti-HIV drugs to the brain. In this review, all the brain delivery techniques available till date has been reviewed and recent noble ideas for delivering anti-HIV drugs to brain has been discussed.