Upper Part Of Gastrointestinal Tract Research Articles

An Review on Floating Mucoadhesive Drug Delivery System

A gastro retentive dosage form will release the drug over an extended period in the stomach and upper gastrointestinal tract (GIT) thus enhancing the opportunity for absorption. Various approaches have been proposed to control the gastric residence of drug delivery system in the upper part of the GIT including floating drug delivery system. Formulation of Gastro-Retentive dosage forms (GRDFs) containing suitable drug candidate which would remain in stomach and/or upper part of GIT for prolonged period of time there by is maximizing the drug release at desired site within the time before GRDFs leave the stomach and or upper part of GIT. Oral route has been the adopted and most convenient route for the drug delivery. Floating dosage forms have been developed to float over GI fluids and to release the drug over a desired period of time. Floating drug delivery system also name as hydrodynamically balanced system (HBS). Bioadhesion can be defined as the process by which a natural or a synthetic polymer can adhere to a biological substrate. When the biological substrate is a mucosal layer then, the phenomenon is known as mucoadhesion.

Restoration of the upper part of gastrointestinal tract and vocal function in patients after laryngectomy

Objective: To improve the outcomes of patients rehabilitation after surgical treatment of local larynx tumors with restoration of the upper part of gastrointestinal tract and vocal function. Materials and methods: Voice prostheses were installed in 243 patients after laryngectomy. Pharyngoplasty with displaced pre-fabricated pectoris flap was performed in 16 patients, voice prosthesis was installed in 9 of them. Reconstruction of pharynx and cervical part of esophagus with visceral flaps was performed in 94 cases, voice prosthesis was installed in 19 of them. Autotransplantation of ilea-colon flap was performed in 1 case, thus providing restoration of digestive and vocal without any prosthesis. This article presents clinical cases of delayed pharyngoplasty with pre-fabricated pectoris flap and visceral flap with installation of voice prosthesis and a case of ilea-colon flap reconstruction. Results: In the group of patients after laryngectomy and voice prosthesis installation, 85% of voice rehabilitation cases were successful, 15% of patients had a spasm of pharynx constrictor muscle, and this required myotomy to be performed. Mouth nutrition after pharyngoplasty with pectoris flap was restored in 94% of patients. 77% of patients had satisfactory speech function after the prosthesis installation. Salivary fistula were observed in 19% of the cases, neck wound maturation – in 6%, flap necrosis – in 6% of the cases. Mouth nutrition after pharyngoplasty with visceral flaps was restored in 94.6% of patients. 84% of patients have good speech generation after prosthesis installation. Salivary fistulas were observed in 8.7% of cases, neck wound maturation – in 6.5% of cases, flap necrosis – in 5.4% of cases. Conclusion: Voice prosthesis installation is possible in patients after all types of pharyngoplasty, except for gastroepiploic flap. The choice of flap for the reconstruction of the upper digestive tract depends on the general condition of the patient, on concomitant pathology, on the state of the donor organs and tissues, on previous surgical intervention on the abdominal organs, and the capabilities of the department.

The microbiota of upper parts of gastrointestinal tract and its role in the development of obesity in children

Evaluation of qualitative and quantitative composition of microflora of different habitats of the human body and definition of their role in the development of metabolic disorders are of great interest for investigators worldwide. The gut microbiota is an obligatory contributor to the synthesis, recirculation and metabolism of steroid hormones, lipids, and bile acids. Infectious agents and their biologically active compounds initiate the atherogenesis. Disorders of lipid metabolism are associated with a change in bacterial enterotypes. Microbiotal colonization of gastrointestinal tract starts at birth. Its composition in a newborn depends on a variety of environmental and nutritional factors, maternal health, the course of pregnancy and delivery. Infants born by cesarean section have a higher incidence of obesity, which is thought to be associated with a delay of bifidobacterial colonization of gastrointestinal tract. Reduction of bifidobacteria counts in the gut in infants below 12 months of age predisposes to obesity in later life. Children born to mothers with obesity have significant differences in the composition of the gut microflora, compared to children born to normal weight mothers. This review presents the data on the association between metabolic disorders, such as obesity and type 2 diabetes, and persistence of Helicobacter pylori infection. Further in-depth research in this area would increase the knowledge on the mechanisms of hormonal and metabolic disorders in childhood and may help to develop algorithms for effective treatment and preventive measures.

IODINE DEFICIENCY AND PATHOLOGY OF THYROID GLAND AS A BACKGROUND STATE OF CANDIDIASIS OF MUCOSA OF THE UPPER PART OF DIGESTIVE TRACT

There were examined 119 patients of gastroenterological profile, who, according to the results of microbiological examination of scraping from tongue and biopsy material of digestive tract and stomach, were divided into three groups: 1 group – patients with oropharyngeal candidiasis and surface candidiasis of mucous tunic, 2 group – patients with invasion of Candida fungi in mucous tunic, 3 group – patients without oropharyngeal candidiasis and without growth of fungi in biopsy material. The status of iodine provision was studied in 78 persons. The results of research revealed that at structural changes of thyroid gland the dominating position in patients with candidiasis of mucous tunic occupies the nodular goiter– 29,31% and 36,36% for 1 and 2 group respectively, whereas in 3 group the frequency of nodular goiter was 11,76%, at that hyperplasia and nodular goiter in patients with fungi invasion in mucous tunic was revealed 2,6 times more often comparing with patients without candidiasis (χ2=4,01; р<0,05). In patients with oropharyngeal and surface candidiasis and invasive candidiasis of mucous tunic of the upper part of digestive tract the hard degree of iodine nutrition deficiency with thyroglobulin level higher than 40 ng/ml was revealed in more than half of cases. At that the frequency of hard iodine deficiency at fungi invasion in mucous tunic 4,2 times higher comparing with patients without candidiasis of mucous tunic (F=0,024; р<0,05). So, the concomitant comorbid state with pathology of thyroid gland and iodine deficiency is an aggravating factor in the course of candida infection that is necessary to be taken into account at clinical monitoring of patients with candidiasis of mucous tunic of the upper part of gastrointestinal tract.

Abstract 382: Concomitant administration of acid reducing agents can impact the pharmacokinetics of the balanced pan-PI3K and mTOR inhibitor PQR309

Abstract Introduction Acid reducing agents (ARAs) - such as proton pump inhibitors, H2-antagonists or antacids - are commonly prescribed medications to reduce stomach acidity in cancer patients. Increased gastric pH can significantly impair the dissolution of agents that exhibit pH-dependent solubility, thus possibly reducing their absorption and influence their pharmacokinetics (PK). PQR309 is a novel oral balanced dual pan-PI3K and mTOR inhibitor currently in clinical development for treatment of solid tumors and hematological malignancies. PQR309 is a weak base and exhibits pH-dependent solubility. Therefore, the assessment of the potential for drug-drug interactions with ARAs is essential to avoid treatment failure in cancer patients. Methods GastroPlusTM v.9.0 (Simulations Plus, Inc.) was used to build a physiologically-based absorption and pharmacokinetic (PBPK) model of PQR309. A baseline model was built with the physicochemical properties of the compound and pre-clinical PK data after iv and po administration. The model was then extended using PK data from cancer patients. Volume of distribution and renal clearance were calculated using the Lukacova and fup*GFR methods, respectively. Hepatic clearance was estimated from in vitro clearance obtained in hepatocytes and the intestinal absorption was calculated by the Advanced Compartmental Absorption and Transit (ACATTM) Model. Results The parameter sensitivity analysis showed that at fasted stomach pH of ∼1.5, PQR309 is fully dissolved and rapidly absorbed in the upper part of gastrointestinal tract leading to a distinct maximum plasma concentration (Cmax) and a predicted bioavailability of almost 100%. At a stomach pH of 4.0 dissolution is delayed and the absorption shifted towards distal parts of the gastrointestinal tract. The predicted bioavailability is still estimated to be good (> 75%), but the observed plasma concentration time profile is much shallower and the expected Cmax considerably reduced. Conclusions Our model predicts that concomitant administration of ARAs can impact PQR309 absorption and change its pharmacokinetic profile. The clinical relevance of this potential drug-drug interaction is unknown. In currently ongoing clinical studies co-medication of PQR309 with ARAs should be avoided until further clinical investigations confirm the model predictions and mitigation strategies are explored. Citation Format: Karin Jorga, Eva Huehn, Grace Fraczkiewicz, Debora Schmitz, Doriano Fabbro, Sasa Dimitrijevic. Concomitant administration of acid reducing agents can impact the pharmacokinetics of the balanced pan-PI3K and mTOR inhibitor PQR309. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 382.

Improving Pharmaceutical Characteristics of Curcumin by Alginate/Pectin Microparticles

This study was aimed at the preparation of curcumin-loaded alginate/pectin microparticles (beads) in order to enhance the pharmaceutical effect of curcumin as a drug for colon related diseases. For this purpose, three types of curcumin-loaded beads were prepared with different alginate/pectin ratios (100/0, 75/25 and 50/50) and studied in various experiments including the release of curcumin from beads and swelling of beads in buffer solutions of simulated gastric, intestinal, and colon fluids. The results of curcumin releasing experiments under conditions mimicking stomach to colon transit showed that the beads with higher content of pectin exhibit stronger curcumin entrapment, slower release rate, and lower swelling. Thus, 50/50 alginate/pectin composition has minimum release in the upper parts of gastrointestinal tract (stomach and intestine). However, when these beads reached colonic buffer medium, the curcumin release suddenly increased. Therefore, beads with 50/50 alginate/pectin compositions could be useful as a suitable carrier for curcumin delivery to colon. Moreover, the stability and chemical protection of curcumin encapsulated in these beads was confirmed by high performance liquid chromatography measurements after a period of six months.

Formulation and Evaluation of Floating tablet of Metronidazole for eradication ofHelicobacter pylori

Metronidazole is widely used antimicrobial drug against Gram-negative and Gram-positive anaerobic bacteria. Floating drug delivery systems (FDDS) offer a number of applications for drugs having poor bioavailability because of narrow absorption window in the upper part of gastrointestinal tract. It was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. In the present study hydroxy propyl methyl cellulose (HPMC) and micro crystalline cellulose (MCC) are used in different concentrations and sodium bicarbonate was used as effervescent agent. Five formulations (F1-F5) were prepared and evaluated for various physicochemical parameters like hardness, friability, floating ability and drug release profiles and were found to be within range. In general, these systems can float in the gastric conditions and control the drug release from the tablets. Formulation was optimized on the basis of different tablet properties and drug release pattern in invitro release profile. In this study it was confirmed that the formulations containing polymer like HPMC K15M and MCC showed better floating properties.

A retrospective study of perforation peritonitis in a tertiary care hospital in Uttar Pradesh, India

Background: Perforation peritonitis is a common surgical emergency encountered by surgeon’s world over. The spectrum of this disease including its etiology differs in various countries. The present study was carried out to study the various modes of presentation, clinical features morbidity and mortality of perforation peritonitis in a tertiary care hospital in Uttar Pradesh, India. Methods: This study was conducted on 221 consecutive patients of perforation peritonitis who presented in a period of 2 years (March 2014 to February 2016) in department of surgery, Rohilkhand medical college and hospital, Bareilly, Uttar Pradseh, India. These patients were assessed with respect to clinical presentations, causes, site of perforation, surgical management, postoperative complications and mortality if any. Following resuscitative measures, all patients underwent emergency exploratory laparotomy, where the cause of perforation was explored and controlled. Results: A total of 221 cases of perforation peritonitis were included in the study with mean age of 39.8 years (range = 10 - 70 years). Majority of patients were male with female ratio of 4.02:1. 62% came with complaints of distension and 42% gave positive history of chronic NSAID use. Most common complications were wound infection, septicemia and dyselectrolylemia (49, 40 and 46% respectively). The overall mortality was 12.2%. Conclusions: In the present study, most common site of perforation was the duodenum, the cause being acid peptic disease as a consequence of NSAIDs use. Early recognition, prompt intervention might lead to better outcomes and curtail mortality and morbidity associated with this disease. Highest percentage of perforation was noted in upper part of gastrointestinal tract.

Formulation and Pharmacokinetic Evaluation of Polymeric Dispersions Containing Valsartan.

Valsartan exhibits poor aqueous solubility and dissolution rate limited absorption. The lower solubility in the upper part of gastrointestinal tract (pH-dependant solubility) where its absorption window exists further contributes to the low oral bioavailability of valsartan. The present work was aimed to improve the in vivo pharmacokinetics of valsartan by preparing amorphous polymeric dispersions using Eudragit E 100 as carrier. Eudragit E 100 is a cationic polymer soluble in gastric fluid up to pH 5.0 and exhibits pH-dependent release. Hence, the dispersions prepared using Eudragit E 100 rapidly dissolves at lower pH presenting drug in molecularly dispersed and soluble form at its absorption site. Polymeric solid dispersions were prepared in different drug-to-carrier ratios. The prepared dispersions were evaluated for drug-carrier interactions, solid-state transitions and drug-release properties with the help of Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and in vitro dissolution studies. The optimized formulation containing valsartan was tested in rats for bioavailability and pharmacokinetic parameters and compared with that of valsartan pure drug. The results from FTIR studies indicated no interactions between drug and excipients. DSC studies confirmed reduction in crystallinity of drug. The dissolution studies performed in 0.1N HCl showed significant improvement (p<0.05) in the dissolution of valsartan. In vivo pharmacokinetic studies showed 199% relative bioavailability with significant improvement (p<0.05) in area under the curve compared to valsartan pure drug. Eudragit E 100 can be used to improve the dissolution of drugs that show low solubility at lower pH and thereby enhancing the bioavailability.

Stress-Related Mucosal Disease in Critically Ill Patients

Mucosal damage in Gastro Intestinal (GI) system happens due to stress and is more common in upper part of GI tract in patients admitted to Intensive Care Unit (ICU). This kind of injuries occurs in critically ill patients. Stress ulcer prophylaxis is necessary and increases the gastric (Power of Hydrogen) pH (more than 4) especially in stress exposure time. In this paper we provide an overview of stress ulcer and currently used preventive approaches for this complication in critically ill patients in ICU. Recent promotion in ICU care and increase in scientific knowledge about Stress-Related Mucosal Disease (SRMD) risk factors help us to reduce the number of patients develop stress ulcer. Prophylaxis can prevent significant bleeding and mortality.

In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally.

Evaluation of In Vivo Transfection Efficiency of Eudragit Coated Nanoparticles of Chitosan-DNA: A pH-sensitive System Prepared for Oral DNA Delivery

Background:Success of any gene therapy protocol relies mostly on using an efficient carrier to direct nucleic acid to the place of action. The system should also have transfection ability at release site. Different routes are available for delivering genetic materials to the target organs, amongst them; oral delivery is particularly attractive for certain reasons. However, serious obstacles, like acidic environment of stomach and presence of protease and nuclease enzymes in gastrointestinal (GI) tract, make oral route a highly challenging option.Objectives:The present study suggests preparation of gene nanoparticles (NPs) of chitosan within a layer of Eudragit L100 for oral delivery of nucleic acid. The nanoparticles have some features both in size and polymer properties that can be penetrating enough to transfect epithelial layer cells of intestine and protect the entrapped materials against stomach harsh condition.Materials and Methods:In this experimental study, conducted in Iran, particles were prepared by coacervation technique followed by encapsulation of nanoparticle within a coat of Eudragit L100 using solvent evaporation technique. Formulation behavior was monitored both in vitro and in vivo. Stability of particle construction and release profile of DNA were examined at pH of ± 0.8 environ pKa of Eudragit. Size and zeta potential of particles were measured. To demonstrate transfection efficiency of the constructed carrier, reverse transcription polymerase chain reaction (RT-PCR) was carried out using human insulin specific primers on total RNA extracted from upper part of small intestine of 48-hour post-transfected rats (sampled by simple random selection, n = 3).Results:The mean size and zeta potential of particles were 300 ± 4 nm and 14 ± 0.5 mV, respectively. Encapsulation of this system was 89.6 ± 1.2%. DNA release from batches was less than 12% at pH = 5.2 and more than 60% at pH = 6.8 with significant difference of P < 0.05. RT-PCR product confirmed the presence of insulin transcript of 437 bp in upper intestinal extracts of the transfected rats. No band of DNA was seen after RT-PCR of placebo form of nanoparticles received group.Conclusions:Eudragit coated nanoparticle of chitosan is an efficient choice for oral delivery of DNA to upper part of GI tract.

A Review: Floatable Gastroretentive Drug Delivery System

In the late years, exploratory and innovative progressions have been made in the innovative work of novel medication conveyance frameworks by overcoming physiological inconveniences, for example, short gastric habitation times and capricious gastric purging times. A few methodologies are as of now used in the prolongation of the gastric habitation times, including floating medication conveyance frameworks, swelling and stretching frameworks, polymeric bioadhesive frameworks, adjusted shape frameworks, high-thickness frameworks and other deferred gastric exhausting gadgets. The administration of sickness through solution is entering another period in which developing number of novel medication conveyance frameworks are continuously utilized and are accessible for helpful utilization. Oral maintained discharge gastroretentive measurements structures offer numerous favorable circumstances for medications with assimilation from upper parts of gastrointestinal tract and for those acting mainly in the stomach, enhancing the bioavailability of the pharmaceutical. Floating Gastroretentive Drug Delivery Systems (FGRDDS) is one among the gastroretentive measurements structures used to accomplish delayed gastric living arrangement time. The reason for composing this audit on skimming medication conveyance frameworks (FGRDDS) was to arrange the late writing with unique concentrate on the important instrument of floatation to accomplish gastric maintenance. The late advancements of FGRDDS including the physiological and definition variables influencing gastric maintenance, methodologies to plan single-unit and numerous unit coasting frameworks, and their arrangement and detailing angles are secured in point of interest. This survey likewise compresses the in-vitro strategies, in vivo studies to assess the execution and application of floating frameworks, and applications of these frameworks.

Gastroretentive mucoadhesive tablet of lafutidine for controlled release and enhanced bioavailability

Lafutidine a newly developed histamine H2-receptor antagonist having biological half-life of 1.92 ± 0.94 h due to its selective absorption from upper part of gastrointestinal tract the development of mucoadhesive sustained release drug delivery system is recommended in order to enhance the bioavailability. A mucoadhesive tablets was developed using the natural polymer, sodium alginate, xanthan gum and karaya gum. Mucoadhesion is a complex phenomenon which involves wetting, adsorption and interpenetration of polymer chains. The prepared tablets of various formulations were evaluated for a total mucoadhesion time, buoyancy lag time and percentage drug released. The formulation with xanthan gum showed better results. Thus, it may be useful for prolonged drug release in stomach to improve the bioavailability and reduced dosing frequency. Non-fickians release transport was confirmed as the drug release mechanism from the optimized formulation by Korsmeyer–Peppas. The optimized formulation (B3) showed a mucoadhesive strength >35 g. In vivo study was performed using rabbits by X-ray imaging technique. Radiological evidences suggest that, a formulated tablet was well adhered for >10 h in rabbit’s stomach. Optimized lafutidine mucoadhesive tablets showed no significant change in physical appearance, drug content, mucoadhesive properties and in vitro dissolution pattern after storage at 40 °C temperature 75 ± 5% relative humidity for 3 months.

Studies on development and characterization of gastroretentive drug delivery system for antibiotics: Cefdinir

Aims/objectiveOral SR gastroretentive dosage forms offer many advantages for drugs having absorption from upper GIT and improve the bioavailability of medications that are characterized by narrow absorption window. Cefdinir is a third generation cephalosporin with broad spectrum of activity with low bioavailability (20–30%) and short biological half life (1–2 h). It has better absorption from upper part of gastrointestinal tract. The purpose of present study was to formulate and develop a new GRDDS using bilayered tablet technology for cefdinir as a model drug. MethodsCefdinir bilayer tablets (CBT) were prepared by using double compression cup and core method. First layer, floating matrix layer contained different rate retarding polymers and effervescent mixture. Second layer is loading layer contained cefdinir and fast releasing components (soluble starch, sodium bicarbonate and citric acid). All CBT were evaluated for their pre and post compression parameters. ResultsPrecompression and post compression parameter of all CBT were within the pharmacopeial limits. In vitro buoyancy behavior and matrix integrity study revealed that FLT of optimized formulation was 1.57 ± 0.52 min and the tablet remained floatable throughout the study. In vitro drug release of optimized CBT follows initially first order release upto 30 min (till their release of loading layer), then zero order release upto 12 h and kinetic profile followed the Peppas (R2 = 0.9838) and zero order (R2 = 0.9986). FTIR studies revealed no drug–excipients interactions. Stability studies conducted for optimized formulation did not show any change in physical appearance, drug content, floatability, matrix integrity. ConclusionKinetics of CBT showed biphasic release in the first phase, immediate dose was released in less than 60 min and second phase was released from matrix layer as a controlled zero order fashion. Cefdinir is a suitable drug for development of gastroretentive bilayer tablet.

Influence of Sodium CMC and HPMC on the Physical Characteristics of Ofloxacin Floating Matrix Tablets

Aims: Sustained release floating drug delivery systems or gastro retentive drug delivery systems enables prolonged and continuous input of drug to the upper part of gastrointestinal tract and improves the bioavailability of medication. A new strategy is proposed for the development of floating drug delivery systems of Fluoroquinolone antibiotic, Ofloxacin, a potent moiety for treating UTI’s. Methodology: Various rate retarding polymers like HPMC K4M, HPMC 5 cps and swelling agent as Sodium carboxymethyl cellulose in different proportions were tried and optimized to achieve the drug release for 8 hr. All the formulations were evaluated for floating properties, swelling characteristics and in vitro drug release studies. The in vitro drug release was found to be matrix diffusion controlled. Optimized formulation was subjected to intermediate stability studies at various combinations of temperature and humidity according to ICH guidelines. Results: Lower hardness and higher thickness decreased the floating lag time and increased floating duration. Based on drug release studies, formulation F5 was optimized as the best formulation because it released about 89.27 ±2.6% of the drug at the end of 8 hr while other formulations released not more than 80 ±2.2%. This may be due to high NaCMC content which might have caused excessive channeling, thereby giving a burst release. Optimized formulation F5 was found to follow zero order kinetics with r2 value of 0.993. Conclusion: In conclusion we have been proved that HPMC K4M has retarded the drug release, while HPMC 5cps has facilitated high buoyancy time for the tablets. NaCMC has influenced as channeling agent. Formulation F5 was optimized for its long buoyancy time, prolonged duration of drug release, zero order and diffusion controlled drug release kinetics which can assure 100% bioavailability.

In Vivo Human X-ray Investigation of Combined Polysaccharide Based Drug Delivery Systems Prepared for Colonic Delivery

The present investigation was aimed to assess the in vivo performance of combined polysaccharides based compression coated tablets for colonic delivery using X-ray study. Fast disintegrating core tablets containing barium sulphate was compression coated with guar gum (GG), locust bean gum (LBG) and hydroxyl propyl methyl cellulose (HPMC) in the ratio 3:3:4 with a coat weight of 400mg. The developed barium sulphate coated tablet was subjected for in vivo human X-ray study. X-ray study revealed that the tablet remained intact during its transit through upper part of gastrointestinal tract. The colon arrival time was found to be between 5-8 h. The disintegration of the tablet occurred in the colon between 14 to 16 h by the microflora present in the colon. In conclusion, results of X-ray studies revealed that GG and LBG along with HPMC was found to be promising coating materials for targeting drugs specifically to the colon.

In Vivo Human X-ray Investigation of Combined Polysaccharide Based Drug Delivery Systems Prepared for Colonic Delivery

The present investigation was aimed to assess the in vivo performance of combined polysaccharides based compression coated tablets for colonic delivery using X-ray study. Fast disintegrating core tablets containing barium sulphate was compression coated with guar gum (GG), locust bean gum (LBG) and hydroxyl propyl methyl cellulose (HPMC) in the ratio 3:3:4 with a coat weight of 400mg. The developed barium sulphate coated tablet was subjected for in vivo human X-ray study. X-ray study revealed that the tablet remained intact during its transit through upper part of gastrointestinal tract. The colon arrival time was found to be between 5-8 h. The disintegration of the tablet occurred in the colon between 14 to 16 h by the microflora present in the colon. In conclusion, results of X-ray studies revealed that GG and LBG along with HPMC was found to be promising coating materials for targeting drugs specifically to the colon. Keywords: Colon specific drug delivery system, colon targeting, compression-coat, diclofenac sodium, guar gum, locust bean gum, X-ray imaging and HPMC.

Design and development of microparticulate delivery system of metronidazole: Experimental design methodology

AbstractThis study describes the application of response surface methodology in the optimization of guar gum microspheres for colon‐specific delivery of metronidazole. The effect of varying the relative percent of the four factors used, that is guar gum, glutaraldehyde, swelling time, and stirring speed, has been systematically investigated for identifying their best values to optimize the drug release and encapsulation efficiency as well as to highlight possible interactions among the components. Different batches were prepared according to 24 factorial designs and randomly evaluated for drug release and drug encapsulation efficiency. Analysis of response surface plots allowed identification of the best combination of four levels to minimize drug release in upper part of gastrointestinal tract and maximize the encapsulation efficiency. The scanning electron microscopy was used to characterize the surface of these microspheres. Drug polymer interactions were assessed by differential scanning calorimetry and XRD. The good correspondence between calculated and experimental values indicated in the validity of the generated statistical model. Only a small fraction of drug was released at acidic pH; however, the release of drug was found to be higher in the presence of rat cecal contents, indicating the susceptibility of crosslinked guar gum matrix to colonic enzymes released from rat cecal contents. Metronidazole release kinetics corresponds best to zero‐order model and drug release mechanism was diffusion and swelling controlled. The significance of differences was evaluated by analysis of variance (ANOVA). Differences were considered statistically significant at P &lt; 0.05. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Pharmacokinetic and pharmacodynamic evaluation of floating microspheres of metformin hydrochloride

Metformin hydrochloride (MH), a biguanide antidiabetic, is the drug of choice in obese patients. It is well absorbed from the upper part of gastrointestinal tract and has oral bioavailability of 50% to 60%. The objective of this study was to formulate MH into floating microspheres in order to increase its residence time at the site of absorption and thus improve its bioavailability; and to extend the duration of action along with possibilities of dose reduction. Microspheres were prepared by emulsion solvent evaporation method and evaluated for particle size, entrapment efficiency, buoyancy, and in vitro release; and further characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The pharmacokinetic and pharmacodynamic evaluation of selected formulation was carried out in male Wistar diabetic rats. The data was statistically analyzed by unpaired t-test. A 3.5-fold increase in relative bioavailability was observed. The prolongation of half-life (t1/2) from 4.5 ± 2.41 h to 14.12 ± 4.81 h indicated extended duration of action. Oral glucose tolerance test (OGTT) was analyzed by one-way analysis of variance followed by Dunnet multiple comparison test, a significant decrease (p < 0.05) in the blood glucose levels was observed when formulations were compared with control rats. Hence, MH floating microspheres were tested at 50 mg/kg and 100 mg/kg body weight, OGTT data showed nonsignificant difference (p >0.05). In conclusion, an effective oral antidiabetics treatment can be achieved by formulating MH into floating microspheres which results in increase in bioavailability along with extended duration of action resulting in possible reduction in dose.