Vineet Kumar Rai

Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance

Liver is a vital organ responsible for plethora of functions including detoxification, protein synthesis, and the production of biochemicals necessary for the sustenance of life. Therefore, patients with chronic liver diseases such as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate attention to sustain life and as a result are often exposed to the prolonged treatment with drugs/herbal medications. Lack of site-specific delivery of these medications to the hepatocytes/nonparenchymal cells and adverse effects associated with their off-target interactions limit their continuous use. This calls for the development and fabrication of targeted delivery systems which can deliver the drug payload at the desired site of action for defined period of time. The primary aim of drug targeting is to manipulate the whole body distribution of drugs, that is, to prevent distribution to non-target cells and concomitantly increase the drug concentration at the targeted site. Carrier molecules are designed for their selective cellular uptake, taking advantage of specific receptors or binding sites present on the surface membrane of the target cell. In this review, various aspects of liver targeting of drug molecules and herbal medications have been discussed which elucidate the importance of delivering the drugs/herbal medications at their desired site of action.

Development of cellulosic polymer based gel of novel ternary mixture of miconazole nitrate for buccal delivery.

Aim of the present investigation was to develop cellulosic polymer based mucoadhesive antifungal gel comprising novel ternary mixture of miconazole nitrate (MN) for buccal delivery. Crosslinking of gel was made by adjusting pH with triethanolamine (TEA) and gel formulation was optimized on the basis of flux of MN (0.562-1.751 mg/cm(2)/h) calculated from ex vivo permeation study. Based on statistically validated polynomial equation and plotted response surfaces, B17 was found to be the optimum batch. Texture profile in terms of adhesiveness (3.24 ± 0.012 g), firmness (10.83 ± 0.067 g), spreadability (3.63 ± 0.033 mJ) and extrudability (35.6 ± 0.1 mJ) of B17 was evaluated using a novel instrumental approach. The texture parameters were found to be consistent over 90 days. Ternary mixture containing gel showed broader zone of growth inhibition (32.67-47.33 mm) in comparison to marketed formulation containing pure MN (17.50-40.33 mm) against selected strains of fungi. In conclusion, consistent and effective mucoadhesive antifungal gel of MN with extended residence time in oral mucosa was developed.

Novel drug delivery system: an immense hope for diabetics

Abstract Context: Existing medication systems for the treatment of diabetes mellitus (DM) are inconvenient and troublesome for effective and safe delivery of drugs to the specific site. Therefore, investigations are desired to deliver antidiabetics using novel delivery approaches followed by their commercialization. Objective: The present review aims to provide a compilation on the latest development in the field of novel drug delivery systems (NDDSs) for antidiabetics with special emphasis on particulate, vesicular and miscellaneous systems. Methods: Review of literature (restricted to English language only) was done using electronic databases like Pubmed® and Scirus, i.e. published during 2005–2013. The CIMS/MIMS India Medical Drug Information eBook was used regarding available marketed formulation of antidiabetic drugs. Keywords used were “nanoparticle”, “microparticle”, “liposomes”, “niosomes”, “transdermal systems”, “insulin”, “antidiabetic drugs” and “novel drug delivery systems”. Single inclusion was made for one article. If in vivo study was not done then article was seldom included in the manuscript. Results: The curiosity to develop NDDSs of antidiabetic drugs with special attention to the nanoparticulate system followed by microparticulate and lipid-based system is found to emerge gradually to overcome the problems associated with the conventional dosage forms and to win the confidence of end users towards the higher acceptability. Conclusion: In the current scientific panorama when the area of novel drug delivery system has been recognized for its palpable benefits, unique potential of providing physical stability, sustained and site-specific drug delivery for a scheduled period of time can open new vistas for precise, safe and quality treatment of DM.

A Novel Approach for Development and Characterization of Effective Mosquito Repellent Cream Formulation Containing Citronella Oil

Citronella essential oil (CEO) has been reported as an excellent mosquito repellent; however, mild irritancy and rapid volatility limit its topical application. It was aimed to develop a nonirritant, stable, and consistent cream of CEO with improved residence time on skin using an industrial approach. Phase inversion temperature technique was employed to prepare the cream. It was optimized and characterized based on sensorial evaluation, emulsification, and consistency in terms of softness, greasiness, stickiness, and pH. The optimum batch (B5) was evaluated for viscosity (90249.67 ± 139.95 cP), texture profile with respect to firmness (38.67 ± 0.88 g), spreadability (70.33 ± 0.88 mJ), and extrudability (639.67 ± 8.09 ± 0.1 mJ) using texture analyzer along with two most popular marketed products selected as reference standard. Subsequently, B5 was found to be stable for more than 90 days and showed enhanced duration of mosquito repellency as compared to CEO. HS-GC ensured the intactness of CEO in B5. Investigated primary irritation index (PII 0.45) positioned B5 into the category of irritation barely perceptible. The pronounced texture profile and stability of B5 with extended residence time and less PII revealed its potential application in industry and offered a promising alternative to the marketed products of synthetic origin.

Solubility enhancement of miconazole nitrate: binary and ternary mixture approach

Abstract Context: Enhancement of aqueous solubility of very slightly soluble Miconazole Nitrate (MN) is required to widen its application from topical formulation to oral/mucoadhesive formulations. Objective: Aim of the present investigation was to enhance the aqueous solubility of MN using binary and ternary mixture approach. Materials and methods: Binary mixtures such as solvent deposition, inclusion complexation and solid dispersion were adopted to enhance solubility using different polymers like lactose, beta-cyclodextrin (β-CD) and polyethylene-glycol 6000 (PEG 6000), respectively. Batches of binary mixtures with highest solubility enhancement potentials were further mixed to form ternary mixture by a simple kneading method. Drug polymer interaction and mixture morphology was studied using the Fourier transform infrared spectroscopy and the scanning electron microscopy, respectively along with their saturation solubility studies and drug release. Results: An excellent solubility enhancement, i.e. up to 72 folds and 316 folds of MN was seen by binary and ternary mixture, respectively. Up to 99.5% drug was released in 2 h from the mixtures of MN and polymers. Discussion: Results revealed that solubility enhancement by binary mixtures is achieved due to surface modification and by increasing wettability of MN. Tremendous increase in solubility of MN by ternary mixture could possibly be due to blending of water soluble polymers, i.e. lactose and PEG 6000 with β-CD which was found to enhance the solubilizing nature of β-CD. Conclusion: Owing to the excellent solubility enhancement potential of ternary mixtures in enhancing MN solubility from 110.4 μg/ml to 57 640.0 μg/ml, ternary mixture approach could prove to be promising in the development of oral/mucoadhesive formulations.

Fabrication and Evaluation of Tinidazole Microbeads for Colon Targeting

Abstract Objective The purpose of present investigation was to develop and evaluate multiparticulate system exploiting pH-sensitive property and specific biodegradability of calcium alginate microbeads, for colon-targeted delivery of Tinidazole for the treatment of amoebic colitis. Methods Calcium alginate beads containing Tinidazole were prepared by ionotropic gelation technique followed by coating with Eudragit S100 using solvent evaporation method to obtain pH sensitive microbeads. Various formulation parameters were optimized which included concentration of sodium alginate (2% w/v), curing time (20 min) and concentration of pectin (1% w/v). All the formulations were evaluated for surface morphology, particle size analysis, entrapment efficiency and in-vitro drug release in conditions simulating colonic fluid in the presence of rat caecal (2% w/v) content. Results The average size of beads of optimized formulation (FT4) was found to be 998.73±5.12 μm with entrapment efficiency of 87.28±2.19 %. The invitro release of Eudragit S100 coated beads in presence of rat caecal content was found to be 70.73%±1.91% in 24 hours. Data of in-vitro release was fitted into Higuchi kinetics and Korsmeyer Peppas equation to explain release profile. The optimized formulation (FT4) showed zero order release. Conclusions It is concluded that calcium alginate microbeads are the potential system for colon delivery of Tinidazole for chemotherapy of amoebic infection.

Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: Formulation development, stability issues, basic considerations and applications

Abstract The use of nanoemulsion in augmenting dermal and transdermal effectiveness of drugs has now well established. The development of nanoemulsion based semisolid dosage forms is an active area of present research. However, thickening or liquid‐to‐semisolid conversion of the nanoemulsions provides opportunities to the formulation scientist to explore novel means of solving instability issues during transformation. Extending knowledge about the explicit role of nature/magnitude of zeta potential, types of emulsifiers and selection of appropriate semisolid bases could place these versatile carriers from laboratory to industrial scale. This article reviews the progressive advancement in the delivery of medicament via nanoemulsion with special reference to the dermal and transdermal administration. It is attempted to explore the most suitable semi solid dosage form for the particular type of nanoemulsion (o/w, w/o and others) and effect of particle size and zeta potential on the delivery of drugs through dermal or transdermal route. Finally, this review also highlights the basic principles and fundamental considerations of nanoemulsion manufacture, application of nanoemulsion based semisolid dosage forms in the dermal/transdermal administration and basic considerations during the nanoemulsion absorption into and through skin. Graphical abstract Figure. No Caption available.

An Assessment of Wound Healing Potential of Argyreia speciosa Leaves

In North India, poultice of young unfolded leaves of Argyreia speciosa Linn. (Convolvulaceae) is used for healing wounds. In order to find scientific evidence for the traditional utilization of leaves of A. speciosa in wound healing, this investigation was carried out. A linear incision wound of about 3 cm in length and 2 mm in depth and circular excision wound of 177 mm2 full thickness were made on the dorsal region of separate groups (n = 5) of anesthetized Swiss albino mice. A simple ointment, developed by including ethanol, ethanol-water, and water extracts (10% each, separately) of A. speciosa, was applied topically to mice once daily for 14 days after wounding. To evaluate the effect of each extract, wound contraction, epithelization period, wound breaking strength, and hydroxyproline content were determined. The water extract of A. speciosa showed accelerated wound healing activity as evidenced by fast wound contraction (96.30 ± 0.52%; P < 0.01), rapid epithelization period (11.40 ± 0.60 days; P < 0.001), greater wound breaking strength (376.56 ± 21.16 g; P < 0.001), and higher hydroxyproline content (16.49 ± 1.12 mg/g; P < 0.05) of granulation tissue. The present report supports the traditional use of Argyreia speciosa leaves for wound healing and signify its relevant therapeutic potential.