ABSTRACT
The major concern with the use of some synthetic excipients is their safety towards biological tissues, hence influencing the reliability of products. With the aim to minimize dependency on highly toxic synthetic excipients, the present study was designed to deliver metronidazole (MNZ) into the colonic region for localized treatment of amoebiasis using natural polysaccharide-based drug delivery. Compression-coated tablets were prepared using water extractable natural polysaccharide from Trigonella foenum-graecum (FG). Physical properties of the tablets were evaluated and dissolution study was performed at pH 1.2, 6.8, and 7.4 with rat cecal material. Results indicate that all batches demonstrated pH-dependent drug release and prevented release into the stomach, allowing traces into the intestine and highest availability into the colon. A significant correlation (r2 = 0.975) was found between the coating levels of extracted polysaccharide and lag time release of drug. Gamma scintigraphy images of in vivo study conducted on human volunteers showed a small intestinal transit time, i.e., 3-5 (4.2 ± 0.4) h and confirmed that the tablets reached the colon within 6-8 h. The present study revealed that the FG polysaccharide-based double compression tablets may be promising colon-specific drug carriers with reduced toxic effects of commonly used synthetic excipients.
Subject(s)
Colon/diagnostic imaging , Drug Carriers/administration & dosage , Drug Discovery/trends , Plant Extracts/administration & dosage , Polysaccharides/administration & dosage , Trigonella , Animals , Colon/drug effects , Colon/metabolism , Drug Carriers/chemistry , Drug Carriers/metabolism , Drug Delivery Systems/methods , Humans , Plant Extracts/chemistry , Plant Extracts/metabolism , Polysaccharides/chemistry , Polysaccharides/metabolism , Radionuclide Imaging/methods , Rats , Reproducibility of Results , Spectroscopy, Fourier Transform Infrared/methods , TabletsABSTRACT
Radioactive skin contamination is one of the most likely risks which occurs after accidental or occupational radiological accidents apart from internal contamination. In such cases where the radioactive contamination has occurred, the person who is contaminated should be decontaminated as early as possible to reduce the damaging health effects of radiation. In the present study, the decontamination efficiency of a developed skin decontamination kit "dermadecon" has been evaluated in animal models and human subjects using gamma scintigraphy. Decontamination efficiency (percentage of the radioactive contaminant removed) was calculated for each radioactive isotope of the study and compared with control where general washing procedure was followed using liquid and soap. The effectiveness of the kit was calculated in animal model with respect to 99mTc-sodium-pertechnetate (99mTcO4-), 201TlCl and 131I and was found 92.84 ± 4.9%, 91.18 ± 3.23% and 94.67 ± 2.92%, respectively. Whereas, in case of human skin, the decontamination efficiency for 99mTcO4- was observed to be 95.00 ± 3.21%. On the basis of findings from the study, it can be concluded that the decontamination agents of the used skin decontamination kit are effective for removal of localized radioactive contaminants from skin, as compared with normal decontamination using soap and water.
Subject(s)
Decontamination/methods , Iodine Radioisotopes/analysis , Technetium/analysis , Thallium Radioisotopes/analysis , Acetic Acid/chemistry , Adult , Animals , Cetrimonium , Cetrimonium Compounds/chemistry , Chelating Agents/chemistry , Edetic Acid/chemistry , Humans , Hypochlorous Acid/chemistry , Iodine Radioisotopes/chemistry , Male , Middle Aged , Oxidants/chemistry , Radionuclide Imaging , Rats, Sprague-Dawley , Reducing Agents/chemistry , Skin , Sodium Bicarbonate/chemistry , Technetium/chemistry , Thallium Radioisotopes/chemistry , Thiosulfates/chemistry , Young AdultABSTRACT
Calcium chloride is an essential calcium channel agonist which plays an important role in the contraction of muscles by triggering calcium channel. First time hypothesized about its role in the treatment of GER (gastro-esophageal reflux) and vomiting disorder due to its local action. There are two objectives covered in this study as first, the development and optimization of floating formulation of calcium chloride and another objective was to evaluate optimized formulation through gamma scintigraphy in human subjects. Gastro retentive formulation of calcium chloride was prepared by direct compression method. Thirteen tablet formulations were designed with the help of sodium chloride, HPMC-K4M, and carbopol-934 along with effervescing agent sodium bicarbonate and citric acid. Formulation (F8) fitted best for Korsmeyer-Peppas equation with an R2 value of 0.993. The optimized formulation was radiolabelled with 99mTc-99 m pertechnetate for its evaluation by gamma scintigraphy. Gastric retention (6 h) was evaluated by gamma scintigraphy in healthy human subjects and efficacy of present formulation confirmed in GER positive human subjects. Gamma scintigraphy results indicated its usefulness in order to manage GERD. Stability studies of the developed formulation were carried out as per ICH guidelines for region IV and found out to be stable for 24 months.
Subject(s)
Acrylates/chemistry , Calcium Channels/metabolism , Gastroesophageal Reflux/metabolism , Radionuclide Imaging , Radiopharmaceuticals/chemistry , Sodium Bicarbonate/chemistry , Tablets/administration & dosage , Technetium/chemistry , Administration, Oral , Biological Availability , Calcium Channels/chemistry , Chemistry, Pharmaceutical , Humans , Radiopharmaceuticals/metabolism , Sodium Bicarbonate/metabolism , Tablets/chemistryABSTRACT
Tinidazole is a versatile anti-amoebic and anti-anaerobic drug used in treatment of intestinal infection. The aim of present study was to develop and evaluate a guar gum based novel target release Tinidazole matrix tablet in animal models and healthy human volunteer using Gamma Scintigraphy technique. Anti-anaerobic and anti-protozoal activity of the developed formulation was studied in vitro against Bacteroides fragilis and Dentamoeba fragilis. Tinidazole was successful radiolabelled with (99m)Tc-pertechnetate using stannous chloride as a reducing agent and stable up to 24h in normal saline and serum. Radiolabeled formulation was evaluated in 6 Newzealand white rabbits by gamma Scintigraphy in static manner up to 24h for its retention in gastrointestinal tract (GIT). Similar set of study was conducted in 12 healthy human volunteers for similar objective Scintigraphy images of healthy human volunteer showed retention of optimized formulations in stomach up to 60min, from where it moved to duodenum further and reached ileum in around 5h. However, initiation of drug release was observed from intestine at 7h. Complete dissociation and release of drug was observed at 24h in colon due to anaerobic microbial rich environment. Results drawn from Scintigraphy images indicate that radiolabeled (99m)Tc-Tinidazole tablet transit through upper part of GI without disintegration. Hence the developed matrix tablet may have a role in treatment of intestinal infection caused by anaerobic bacteria.
