Part Of GIT Research Articles

Development of hollow/porous floating beads of metoprolol for pulsatile drug delivery

The purpose of this work was to develop hollow calcium pectinate beads for floating pulsatile release of metoprolol tartrate intended for chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, hollow/porous beads were prepared by simple process of acid-base reaction during ionotropic cross-linking using low methoxy pectin, xanthan gum, sodium carboxy methyl cellulose, guar gum, locust bean, gellan gum and calcium chloride as a cross-linking agent. Based on the preliminary studies optimized polymers were selected for formulation design with different polymers ratio concentrations. The obtained floating beads were studied for entrapment efficiency, buoyancy study, swelling index, surface morphology, in vitro release, stability studies and in vivo floating study. The floating beads obtained were porous, float up to 12-24h. The radiological studies (X-rays) pointed out the capability of the system to release drug in lower parts of GIT after a programmed lag time for hypertension. The floating beads provided expected two-phase release pattern with initial lag time during floating in acidic medium followed by rapid pulse release in phosphate buffer. From the accelerated stability studies, it was observed that the formulations are quite stable. All formulations followed first-order release kinetics by diffusion mechanism. This approach suggested the use of hollow calcium pectinate microparticles as promising floating pulsatile drug delivery system for site- and time-specific release of drugs acting as per chronotherapy of diseases.

The Dual Positive Actions of Colonic Release of Ibuprofen in TNBS-Induced Colitis Wistar Rats

Ibuprofen is a relatively safe anti inflammatory drug among other NSAIDs. However, frequent and long-term administration of ibuprofen in conventional oral preparation is still considered for ulceration. As previously reported, the daily administration of the ibuprofen orally for 14 days in rats caused the gastroduodenal ulcer. Several mechanisms have been reported: the suppression of the gastric prostaglandin synthesis and the local irritant effect on epithelium due to the direct contact of drug with mucosal wall. In this work, developed ibuprofen pellet with double coatings aimed to release ibuprofen only when reaching colonic compartment. The results of pharmacokinetic study reported previously suggested that this might be a successful target. Present study described the potential benefits of this formula in exhibiting effective local anti inflammatory action in colon. Male Wistar rats were induced for ulcerative colitis with 2,4,6-trinitrobenzene sulfonic acid. Twenty four hours after induction, treatments were given using either ibuprofen suspension or pellet for 14 days. Ulcerations were observed visually, with gross anatomic and microscopic examinations. Group treated with ibuprofen pellet showed best recovery nearly close to healthy group. Moreover, the group did not develop ulceration in upper part of GIT. Colonic targeted ibuprofen pellet showed most effective local antiinflammatory action and at the same time reduced the ulcer formation in the upper part of GIT.

Exploiting microspheres as a therapeutic proficient doer for colon delivery: a review

Introduction: Colon-specific drug delivery systems have recently gained importance for delivering a variety of therapeutic agents via oral route. This mode offers the feasibility of treating colonic pathologies with less risk of bioburden to other organs/tissues and has been widely researched for the delivery of challenging drugs. Microspheres targeted to colon have occupied central position on drug delivery due to their small size that offers characteristic intrinsic properties attributable to the carrier.Areas covered: The present deliberation precariously covers the capacious usage of microspheres for the treatment of local colonic pathologies like colon carcinomas, inflammatory bowel disease and parasitic diseases using natural as well as synthetic carriers. The write up also encompasses clinical application of microspheres.Expert opinion: Microspheres have comprehensive potential to be marketed as the patient-friendly formulation, as it would provide direct treatment at the disease site and, consequently, lower dosing and reducing systemic side effects. Wherefore, the major obstacles in delivering drugs to the colon like the absorption and degradation pathways in the proximal part of GIT could be easily overcome, and also a range of pathologies from constipation and diarrhea to the exhaustive inflammatory bowel diseases and colon carcinoma could be cured.

Development and in-vitro evaluation of mucoadhesive gastroretentive matrix tablets of cephalexin

Cephalexin is a semi-synthetic cephalosporin β-lactum antibiotic intended for oral administration used to treat urinary tract infections, respiratory tract infections, skin and soft tissue infections. The present investigation concerns the development and evaluation of single unit mucoadhesive drug delivery system of cephalexin. Mucoadhesive drug delivery system (MDDS) prevents degradation and remains the drug release in stomach or upper part of GIT for prolonged period of time, therefore the maximum drug release is maintained at desired site. After oral administration, are designed to prolong the gastric residence time, increase drug bioavailability and target the gastric infections. A mucoadhesive drug delivery system was developed using like mucoadhesive polymers and hydrocolloids, like hydroxypropyl methylcellulose (HPMC K100M), carbopol 934P and Sodium carboxy methyl cellulose (Sodium CMC). The prepared tablets were evaluated in terms of their physical characteristics, in vitro release, swelling index, mucoadhesive strength and scanning electron microscopy of optimized formulation. The formulations were optimized for different concentrations of HPMC, carbopol and Sodium CMC. The results of the in vitro release studies showed that the optimized formulation could sustain drug release for 12 h. The comparison of drug release profile of all formulations showed that formulations Fa1 which contains more amount of Carbopol 934p and fewer amounts of HPMC K100M and

Pectin–metronidazole prodrug bearing microspheres for colon targeting

The present study explored the potential of pectin–metronidazole (PT–ME) prodrug bearing microspheres for colon delivery. PT–ME prodrug was synthesized with different degree of substitution. The success of the synthesis was confirmed by spectroscopy. PT–ME microspheres and pectin microspheres bearing plain metronidazole were prepared using emulsion-dehydration technique. Microspheres were evaluated for shape and surface morphology, size distribution, entrapment efficiency and in vitro drug release in simulated gastrointestinal fluids (SGF). Microspheres prepared from PT–ME prodrug were not only exhibiting increased the drug entrapment efficiency, but the drug release at the upper part of GIT was also reduced as compared to pectin microspheres having physically entrapped drug. In vitro drug release studies were showing no drug release at acidic pH from microspheres prepared by drug polymer prodrug while pectin microspheres having physically entrapped drug showed almost or complete drug release. In vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of microspheres prepared from PT–ME prodrug as compared to pectin microspheres having physically entrapped drug. Hence, it can be concluded that microspheres prepared from PT–ME prodrug deliver the drug more efficiently to colon.

Formulation and Evaluation of Polymeric Nanoparticles of an Antiviral Drug for Gastroretention

The aim of present study was to formulate and evaluate nanoparticles of acyclovir by using different hydrophilic polymers. Acyclovir was selected as a suitable drug for gastro-retentive nanoparticles due to its short half life, low bioavailability, high frequency of administration, and narrow absorption window in stomach and upper part of GIT. The nano-precipitation method was used to prepare nanoparticles so as to avoid both chlorinated solvents and surfactants to prevent their toxic effect on the body. Nanoparticles of acyclovir were prepared by using hydrophilic polymers such as bovine serum albumin, chitosan, and gelatin. The prepared formulations were then characterized for particle size, polydispersity index, zeta potential, loading efficiency, encapsulation efficiency and drug-excipient compatibility. The prepared nanoparticulate formulations of acyclovir with different polymers in 1:1 ratio have shown particle size in the range of 250.12-743.07 nm, polydispersity index (PDI) in the range of 0.681-1.0, zeta potential in the range of -14.2 to +33.2 mV, loading efficiency in the range of 8.74-17.54%, and entrapment efficiency in the range of 55.7%-74.2%. Nanoparticulate formulation prepared with chitosan in 1:1 ratio showed satisfactory results i.e. average particle size 312.04 nm, polydispersity index 0.681, zeta potential 33.2 mV, loading efficiency 17.54%, and entrapment efficiency 73.4%. FTIR study concluded that no major interaction occurred between the drug and polymers used in the present study.

Floating microspheres of valacyclovir HCl: Formulation, optimization, characterization, in vitro and in vivo floatability studies

Floating microspheres are multiple unit Gastroretentive drug delivery systems. Valacyclovir hydrochloride (VCH) is L-valyl ester prodrug of acyclovir. VCH degrades in intestinal fluid. The objective was to develop floating microspheres of VCH to localise the drug at upper part of GIT, for improved absorption. Floating microspheres were prepared by W/O emulsification solvent evaporation method using Ethylcellulose (EC) as polymer. Particle size and % EE were 550.021±0.241 μm, 79.88±2.236% respectively. in vitro and in vivo floatability studies confirmed floating behaviour of microspheres. VCH loaded floating microspheres can be a suitable alternative to the conventional formulation, by localizing the drug at upper GIT.

An investigation of formulation factors affecting feasibility of alginate-chitosan microparticles for oral delivery of naproxen

In the present work we investigated the feasibility of chitosan treated Ca-alginate microparticles for delivery of naproxen in lower parts of GIT and evaluated influence of formulation factors on their physicochemical characteristics and drug release profiles. Investigated factors were drug/polymer ratio, chitosan molecular weight, chitosan concentration in hardening medium, and hardening time. Sixteen microparticle formulations were prepared utilizing 24 full factorial design (each factor was varied at two levels). Microparticles size varied between 262.3 ± 14.9 and 358.4 ± 21.7 μm with slightly deformed spherical shape. Low naproxen solubility and rapid reaction of ionotropic gelation resulted in high encapsulation efficiency (> 75.19%). Under conditions mimicking those in the stomach, after two hours, less than 6.18% of naproxen was released. Significant influence of all investigated factors on drug release rate was observed in simulated small intestinal fluid. Furthermore, experimental design analysis revealed that chitosan molecular weight and its concentration had the most pronounced effect on naproxen release. Release data kinetics indicated predominant influence of a pH-dependent relaxation mechanism on drug release from microparticles.

Gastroretentive Drug Delivery of Metformin Hydrochloride: Formulation and In Vitro Evaluation Using 32 Full Factorial Design

Metformin Hydrochloride (MF) is glucose lowering agent that is widely used for management for type II diabetes. MF is reported to be absorbed mainly in upper part of GIT. It is having narrow absorption window and high water solubility, and it would be more beneficial to retain the drug in stomach for prolonged duration so as to achieve maximum absorption and better bioavailability. A conventional oral CR formulation releases most of the drug content at the colon, which requires that the drug will be absorbed from the colon. The present investigation is aimed to develop novel gastroretentive (GR) drug delivery system, which not only release the drug in the absorption window but also provides controlled release drug profile that may result patient compliance and therapeutic success. Floating tablets of MF was prepared using sodium alginate, and sodium carboxymethylcellulose was used as a gelling agent, and release modifiers, respectively. Eudragit NE 30 D was used as sustained release polymer to control the initial burst release. Drug and excipients compatibility studies were monitored by thermal analysis by using differential scanning calorimeter. 32 full factorial design was applied to optimize the formulation. The DSC thermogram of drug, polymer and physical mixtures revealed that there was no known interaction between drug and polymers. The prepared tablets were evaluated for in vitro dissolution, in vitro buoyancy, percentage swelling, percentage erosion and similarity factors with marketed tablets. The optimization study using a 32 full factorial design revealed that the amount of sodium alginate and sodium carboxymethylcellulose had a significant effect on t50, t90, Flag and f2. Thus, by selecting a suitable composition of release rate modifier and gel forming agent, Gastro retentive system can be developed with the desired dissolution profile. This study indicated that the MF GR tablets prepared using sodium alginate and sodium carboxymethylcellulose can successfully be employed as a once-a-day oral controlled release drug delivery system.

Time and pH dependent colon specific, pulsatile delivery of theophylline for nocturnal asthma

In this study, investigation of an oral colon specific, pulsatile device to achieve time and/or site specific release of theophylline, based on chronopharmaceutical consideration. The basic design consists of an insoluble hard gelatin capsule body, filled with eudragit microcapsules of theophylline and sealed with a hydrogel plug. The entire device was enteric coated, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. The theophylline microcapsules were prepared in four batches, with Eudragit L-100 and S-100 (1:2) by varying drug to polymer ratio and evaluated for the particle size, drug content and in vitro release profile and from the obtained results; one better formulation was selected for further fabrication of pulsatile capsule. Different hydrogel polymers were used as plugs, to maintain a suitable lag period and it was found that the drug release was controlled by the proportion of polymers used. In vitro release studies of pulsatile device revealed that, increasing the hydrophilic polymer content resulted in delayed release of theophylline from microcapsules. The gamma scintigraphic study pointed out the capability of the system to release drug in lower parts of GIT after a programmed lag time for nocturnal asthma. Programmable pulsatile, colon-specific release has been achieved from a capsule device over a 2–24 h period, consistent with the demands of chronotherapeutic drug delivery.

Gastrointestinal toxicity of melos conquer mixture in rats.

GIT effects of Melos Conquer Mixture were investigated - using albino wister rats. Conquer Mixture was administered orally at different concentrations whereas the control group received water. The experiment lasted from 3 to 21 days. Pathological examination was carried out on the dead animals. The animals showed (1) loss of weight and appetite (2) weakness (3) faeces was soft (4) out of 10 animals which received 1.20 ml/kg died on day 5(5) the Glt of the dead rats was virtually empty except in the colon, (6) pieces from various parts of GIT revealed evidence of acute and sub acute inflammatory cellular reactions. The results indicate that Conquer Mixture may be toxic to the gastrointestinal tract and suggest that a re-evaluation of the therapeutic usefulness of the drug in the management of malaria is warranted.

Formulation and in vitro Evaluation of Gastroretentive Drug Delivery System for Ranitidine Hydrochloride

The purpose of this investigation was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Currently, floating tablets are one of the important categories of drug delivery systems with gastric retentive behavior. Ranitidine is a H2 blocker and absorbed from the upper part of GIT and hence there is need to develop a dosage form that releases the drug in stomach so that it can be absorbed from upper part of GIT leading to improved bioavailability. Six different gastroretentive tablets of ranitidine HCl were prepared by direct compression using different concentrations of Hydroxy propyl methyl cellulose (HPMC K4M), Carbopol, Sodium carboxy methyl cellulose, sodium bicarbonate and citric acid. The formulations were coded as HE1, HE2, HC1, HC2, HEC1 and HEC2. The formulations were evaluated for pharmacopoeial quality control tests and all the physical parameters evaluated for quality control were within the acceptable limits of Pharmacopoeia. All the formulations were subjected to in vitro drug release study and compared with that of marketed formulation. The floating lag time of the prepared formulations is good except for one formulation (HC1) and the floating time for all the formulations was >12 hours except HC1 which does not float at all. In conclusion, effervescent is essential for the formulation to have good floating property and carbopol retards the drug release in floating formulations. The statistical analysis of the parameters dissolution efficiency of dissolution data, floating behavior and drug content after storage at 40°C and 75% RH for three months showed no significant change by Student’s t-test indicating that formulation (HEC1) could provide a minimum shelf life of 2 years.