Formulation and pharmacodynamic evaluation of glibenclamide incorporated niosomal gel.

OBJECTIVE: The research aims to formulate and develop the controlled release profile of glibenclamide by encapsulating glibenclamide into niosomes followed by incorporation into an aqueous gel base. MATERIALS AND METHODS: Glibenclamide incorporated niosomes were prepared by a modified ether injection technique using Span 20/Span 80 and cholesterol. The prepared niosomes were evaluated for chemical incompatibility by FT-IR, morphology, vesicle dimension, encapsulation efficiency, in-vitro diffusion and drug release kinetics. Niosomal gels were prepared by incorporating the optimized niosomes into a gel base containing Carbopol 934 and evaluated for viscosity, in-vitro diffusion and in-vivo pharmacodynamic activity. RESULTS AND DISCUSSION: The results indicated that relationship between the amount of Span and niosomal vesicular diameter was inversely proportional. Microscopic images have illustrated the sphere shape vesicles. The cumulative percentage of drug release from niosomal suspension was observed in the order GN-4>GN-2>GN- 6>GN-5>GN-3>GN-1. Glibenclamide gel showed highest percentage drug release when compared to niosomal gel. Invivo study revealed that the glibenclamide incorporated niosomal gel formulation; GNG-1 is more efficient in lowering blood glucose levels in experimental animals. CONCLUSION: The niosomal gel of glibenclamide had released the drug in well controlled manner which is supported by pharmacodynamic activity with evidence of consistent lowering of blood glucose levels.

Assessment of hupu gum for its carrier property in the design and evaluation of solid mixtures of poorly water soluble drug - rofecoxib.

There are no reports about the pharmaceutical applications of hupu gum (HG). Hence the present study was undertaken to test its suitability in the dissolution enhancement of poorly water soluble drug. Rofecoxib (RFB) was taken as model drug. For comparison solid mixtures were prepared with carriers such as poly vinyl pyrrolidone (PVP), sodium starch glycollate (SSG) and guar gum (GG). Physical mixing (PM), co-grinding (CG), kneading (KT) and solvent evaporation (SE) techniques were used to prepare the solid mixtures, using all the carriers in different carrier and drug ratios. The solid mixtures were characterized by powder X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR). There was a significant improvement in the dissolution rate of solid mixtures of HG, when compared with the solid mixtures of other carriers. There was an increase in dissolution rate with increase in concentration of HG upto 1:1 ratio of carrier and drug. No drug-carrier interaction was found by FTIR studies. XRD studies indicated reduction in crystallinity of the drug with increase in HG concentration. Hence HG could be a useful carrier for the dissolution enhancement of poorly water soluble drugs.

Modified pulsincap of ibuprofen--a novel approach for chronotherapy.

The aim of the present work was to develop colon specific drug delivery system for ibuprofen using natural polymers as carriers. We have investigated colon specific, pulsatile device to achieve time and site specific release of ibuprofen based on chronopharmaceutical considerations. The basic design consists of an insoluble hard gelatin capsule body, filled with ibuprofen surface solid dispersions and sealed with guar gum hydrogel plug. The entire capsule was coated with ethyl cellulose, so that the variability in gastric emptying time can be overcome and a colon specific release can be achieved. Surface solid dispersions (SSDs) of ibuprofen were prepared using natural polymers such as Guar gum (GG), Hupu gum (HG) and Xanthan gum (XG) in the weight ratios of 1:0.5, 1:1 and 1:2 by using solvent evaporation method. Physicochemical properties of the prepared SSD were characterized by FTIR and DSC. Optimized SSD were obtained by practical yield, drug content, solubility and dissolution studies and were selected for further fabrication of pulsincaps. Guar gum was used as hydrogel plug material to maintain a suitable lag period. The prepared pulsincaps were evaluated for in-vitro release. Pulsincap formulated with Ibuprofen-Hupu gum (PF3) at 1:2 ratio of surface solid dispersions showed highest drug release over the period of 12 hr and release was found to be Higuchi model kinetics. The present research study results have confirmed that the modified pulsincap of ibuprofen is a suitable device for the time dependent and site specific delivery to the colon segment of GIT.

Receptors and ligands role in colon physiology and pathology.

Colonic diseases are more prevalent during the past decade. Colorectal cancer, ulcerative colitis, Crohn's disease, diverticulitis, irritable bowel syndrome are the major reported colonic diseases. Innovative strategies are defensible in order to advance the efficacy of colonic disease treatment. During the past decade there has been an extensive advance in the understanding of receptor signaling both from a clinical as well as a preclinical perspective. A sound knowledge on molecular pathways that characterize cell growth, cell cycle, apoptosis, angiogenesis and invasion has provided novel targets in colorectal cancer therapy and inflammatory pathways in the ulcerative colitis. Receptor signaling has been involved in these pathways. To understand the receptor ligand interaction, one must have the basic knowledge regarding those receptors and ligands. This review summarizes the existing knowledge of the expression and function of various receptors and ligands in the colonic tissue. It also covers their role in the physiological processes and pathological conditions of colon.

Anatomical, biochemical and physiological considerations of the colon in design and development of novel drug delivery systems.

The colon is composed of four distinct layers such as serosa, muscularis externa, sub mucosa and mucosa. There exists a difference in the anatomy, neural and blood supply and absorption characteristics as the length of the colon is traversed. At birth the mucosal surface of the colon is similar to that of the small intestine but rapid changes occur with the loss of the villi leaving flat mucosa with deep crypts. The existence of receptors like muscarinic M3, cholecystokinin1, Eph, Erb B, estrogen (α, ß), gastrin releasing peptide, killer Ig like receptor, lymphocyte-endothelial receptor, notch, pregnane X, substance P and peroxisome proliferator-activated γ receptor can be utilized as a promising approach for targeting. The inner compact firm mucus is impervious to bacteria, making it a defensive barrier for the colossal bacterial load. The mucus thus provides innate immunity to maintain the homeostasis in colon. The physiological properties of the colon such as pH, transit time, luminal pressure of the colon, and the presence of microbial flora localized in the colon are utilized in the drug design. The drug delivery systems exploit enteric coating and biodegradable polymers to reach colon in an intact form by surpassing the barriers in the stomach and small intestine. The presence of azo-reductase, glucuronidase, dextranase, pectinase, glycosidase, polysaccharidase made it feasible to design prodrug and enzyme based drug delivery. Drug designing methodologies in colon specific drug delivery include pH- based systems, enzymedepended systems, timed- release systems and pressure/osmotically release systems.