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The investigation was aimed at developing thermodynamically stable topical delivery system of nanostructured lipid carrier of econazole nitrate (EN) for the treatment of deep seated fungal infection by improving its permeability. Fifteen formulations (F1-F15) of nanostructured lipid carriers (NLCs) were prepared by solvent injection technique using central composite design and characterized for particle size and % entrapment efficiency. Closeness in the results, guided the selection of five NLC formulations which were formulated as hydrogels (G1-G5) using Carbopol 934. The permeation studies of gels demonstrated G3 with flux rate of 3.21 ± 0.03 μg/cm(2)/min (> target flux of 1.46 μg/cm(2)/min) as the best formulation that exhibited zero order permeation. The amount of drug/unit area demonstrated linear dependency on flux rate. Confocal laser scanning microscopy demonstrated penetration of rhodamine red till the stratum basale due to hydration of stratum corneum. Hydrogel G3 containing NLC formulation (F5) was selected as the optimized topical gel. TEM of F5 revealed spherical particles that presented low recrystallization index of 72.35%. Stability profile for 90 days revealed insignificant change (p < 0.05) in the particle size and zeta potential indicating substantial stability of the system. Thus, EN-loaded NLC indicated better permeability and thermodynamic stability as effective topical delivery system for deep seated fungal infection. Source


Pathak K.,Rajiv Academy for Pharmacy
Expert Opinion on Therapeutic Targets | Year: 2014

Introduction: The discovery of IL-7 and thymic stromal lymphopoietin (TSLP) has been a major step in the understanding of arthritis. IL-7 amplifies the inflammation induced by other cytokines, primarily TNF. In animal models of arthritis, inhibition of IL-7 limits inflammation and joint erosion. TSLP is an IL-7-like cytokine that triggers dendritic cell-mediated Th2-type inflammatory responses and is considered as a master switch for allergic inflammation. TSLP is a downstream molecule of TNF-α and as such may be involved in the pathophysiology of inflammatory arthritis. Areas covered: This review summarizes current knowledge of the role of IL-7 and TSLP derived from both animal models and studies in patients with rheumatoid arthritis (RA). The emergence of IL-7 blockade as a future therapy in RA is highlighted, along with the potential goals and limitations of this therapeutic approach. The write-up also highlights the functional capacities of TSLP in arthritis. Expert opinion: Evidences suggest important roles for IL-7 and TSLP in the pathogenesis of RA and can be viewed as potential therapeutic targets. Regulation of these at genetic level is a promising investigational area. Given the difficulty in reconstituting T cells in patients with RA, therapeutic approaches that minimize the elimination of T cells are likely to be more desirable. © 2014 Informa UK, Ltd. Source


Sharma G.K.,Rajiv Academy for Pharmacy | Pathak D.,Rajiv Academy for Pharmacy
Chemical and Pharmaceutical Bulletin | Year: 2010

Solvent free microwave assisted synthesis of some novel substituted imidazoles of biological interest is reported. First, primary aromatic or heteryl amine was condensed with aryl or heteryl aldehydes to afford corresponding Schiff's base. The Schiff's base further on treatment with ammonium acetate (NH 4OAC) and isatin using silica gel as the solid support, yielded the corresponding aryl imidazoles. In this paper a comparative study between the developed microwave method and conventional method is described. The synthesized compounds were analyzed by physical and analytical data. The synthesized compounds were evaluated for their antibacterial, anthelmintic, short-term anticancer and antitubercular activity. All the synthesized substituted imidazoles have shown good antibacterial activity against gram negative bacterial strains Klebsiella pneumoniae and Escherichia coli and moderate to good anthelmintic activity. The synthesized imidazole derivative possessed signifi-cant cytotoxic activity against Ehrlich's ascites carcinoma (EAC) cell lines. None of the compounds exhibited prominent antitubercular activity. © 2010 Pharmaceutical Society of Japan. Source


Sharma P.,Rajiv Academy for Pharmacy | Pathak K.,Rajiv Academy for Pharmacy
Expert Opinion on Biological Therapy | Year: 2012

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that is characterized by inflammation of synovial membrane and the release of inflammatory cytokines that ultimately results in joint destruction and disability. The therapeutic treatment plan for treating RA patient initiates with disease-modifying antirheumatic agents (DMARDs) and ends with the use of biological agents. Sometimes a combination of DMARDs and the biological agents are aggressively initiated. But this is not sufficient to retard the underlying progression of the disease and hence the disease-associated pain persists. The solution lies in the treatment of causative factors. Modern therapy aims at targeting newer target sites that can not only overcome the problem of pain and disability but also minimize the occurrence of adverse effects faced by the traditional therapeutic approach. Areas covered: This review covers the pathological background of the disease in brief, the traditional and newer biologicals, therapeutic targets and novel therapies for rheumatoid arthritis. Expert opinion: Better management of the disease can be achieved by focusing on the causes and the factors of the disease. Newer therapies and targeting sites discussed in this review focus on treating the disability at the cellular level without affecting body's immune response and minimizing the chances of infection and inflammation. © Informa UK, Ltd. Source


Pathak K.,Rajiv Academy for Pharmacy | Raghuvanshi S.,Rajiv Academy for Pharmacy
Clinical Pharmacokinetics | Year: 2015

The delivery of drugs through the oral route is regarded as most optimal to achieve desired therapeutic effects and patient compliance. However, poor pharmacokinetic profiles of oral drug candidates remains an area of concern, and approaches to enhance their bioavailability are widely cited in the literature. Traditionally, the approaches have been confined to molecular optimization of the drug molecule, which has gradually evolved into development of microsized and nanosized formulations. Nanoformulations, by virtue of their nanosize, are widely acclaimed for circumventing the obstacles of poor pharmacokinetics. In this review, an attempt has been made to discuss existing challenges of bioavailability and approaches to overcome the same, with in-depth compilation of the literature on nanoformulations. The nanoformulations reviewed include nanocrystals, nanoemulsions, polymeric nanoparticles, self-nanoemulsifying drug delivery systems, dendrimers, carbon nanotubes, polymeric micelles and lipid nanocarriers. This review confirms the potential of nanomedicines to improve the pharmacokinetics of drugs via nanoformulations. Chemotherapeutic applications and patent reports are also compiled in the review. Despite the promising benefits, nanomedicines are associated with hazards to human health. Hence, the review also deals with toxicological consequences of nanomedicines, and with in vitro/in vivo screening methods to assess bioavailability as per regulatory considerations. Nanotechnology has been shown to facilitate the clinical translation of drug candidates that were deemed to be bioavailability failures. Conclusively, nanotechnological approaches to particle design and formulation are beginning to expand the market for many drugs with improved bioavailability and therapeutics. However, dedicated efforts are needed to develop advanced nanomedicines with minimal or no adverse effects. © 2015, Springer International Publishing Switzerland. Source

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