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Oral colon delivery is pursued through a number of formulation strategies with the aim of enabling effective and well-tolerated treatments for large bowel pathologies or enhancing the intestinal absorption of peptide and protein drugs. According to such strategies, coated dosage forms for colonic release may be provided with microbiota, pH, pressure or time-dependent polymeric films. Microbiota-activated coatings are mostly obtained from polysaccharides of natural origin mixed with insoluble structuring excipients. Alternatively, synthetic azo compounds have been employed, generally requiring organic solvents for use as spray-coating agents. On the other hand, pH-sensitive films show responsiveness to pH changes in the lower gut, such as the rise generally observed in the terminal ileum and distal colon or the slight acidification of caecal contents by bacterial fermentation products. Pressure-sensitive coatings are intended for rupturing because of the relatively elevated pressure that may affect solid dosage forms in the large bowel. Finally, time-dependent films are expected to undergo timed erosion, break-up or permeabilization processes irrespective of the aforementioned physiological variables. In this review, the differing films applied for colon delivery purposes are surveyed, and details on their composition, manufacturing and performance are reported., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Oral colon delivery is currently considered of importance not only for the treatment of local pathologies, such as primarily inflammatory bowel disease (IBD), but also as a means of accomplishing systemic therapeutic goals. Although the large bowel fails to be ideally suited for absorption processes, it may indeed offer a number of advantages over the small intestine, including a long transit time, lower levels of peptidases and higher responsiveness to permeation enhancers. Accordingly, it has been under extensive investigation as a possible strategy to improve the oral bioavailability of peptide and protein drugs. Because of a strong underlying rationale, most of these studies have focused on insulin. In the present review, the impact of key anatomical and physiological characteristics of the colon on its viability as a protein release site is discussed. Moreover, the main formulation approaches to oral colon targeting are outlined along with the design features and performance of insulin-based devices., (Copyright © 2011 Elsevier B.V. All rights reserved.)

It is well known that the intestinal stability and absorption of protein drugs are improved when enzyme inhibitors/permeation enhancers are coadministered. Recently, it was hypothesized that an increased effectiveness of these adjuvants might be achieved by timing their release prior to that of the protein, so that a more favorable environment would be established in advance. Therefore, an oral system was proposed for two-pulse colonic release of insulin and the protease inhibitor camostat mesilate/absorption enhancer sodium glycocholate. The device consisted of a drug-containing core, an inner swellable/erodible low-viscosity hydroxypropyl methylcellulose (HPMC) coating, an intermediate adjuvant layer, and an additional outer HPMC coating. HPMC coats and camostat mesilate/sodium glycocholate films with differing thicknesses were applied to immediate-release tablet cores by aqueous spray coating. The obtained units were characterized for weight, thickness, breaking force, and release performance. All systems showed satisfactory technological properties and the pursued pulsatile delivery behavior, with programmable delay phases preceding inhibitor/enhancer release and elapsing between inhibitor/enhancer and protein release, respectively. Indeed, both lag times linearly correlated with the relevant HPMC coating level. The system was thus proven suitable for yielding two-pulse release profiles, in which lag phases could be modulated to provide convenient concentration patterns for proteins and adjuvants., (Copyright © 2011 Wiley-Liss, Inc.)

Oral pulsatile/delayed delivery systems are designed to elicit programmable lag phases preceding a prompt and quantitative, repeated or prolonged release of drugs. Accordingly, they draw increasing interest because of the inherent suitability for accomplishing chronotherapeutic goals, which have recently been highlighted in connection with a number of widespread chronic diseases with typical night or early-morning recurrence of symptoms (e.g. bronchial asthma, cardiovascular disease, rheumatoid arthritis, early-morning awakening). In addition, time-based colonic release can be attained when pulsatile delivery systems are properly adapted to overcome unpredictable gastric emptying and provide delay phases that would approximately match the small intestinal transit time. Oral pulsatile delivery is pursued by means of a variety of release platforms, namely reservoir, capsular and osmotic devices. The aim of the present review is to outline the rationale and main formulation strategies behind delayed-release dosage forms intended for the pharmacological treatment of chronopathologies., (Copyright 2010 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis is a chronic condition that is characterized by joint pain and inflammation. It is an autoimmune disorder in which the body tissues are erroneously attacked by the immune system of the host itself. It has been evident that rheumatoid arthritis symptoms follow a 24 h circadian rhythm and exhibit high thresholds of pain, functional disability, and stiffness predominantly early in the morning. Colon-specific drug delivery systems can be utilized in the formulations to be used in the treatment of rheumatoid arthritis. The colon-specific drug delivery system has shown promising results in the treatment of different diseases at the colonic site like Crohn's disease, ulcerative colitis, colon cancer, etc. The colon-specific drug delivery is capable of delivering the formulation at the predetermined location and predetermined time. The early morning symptoms of rheumatoid arthritis like pain and inflammation can be treated using the various approaches of the colon-specific drug delivery system because it will lead to patient compliance as the patient will not require administering the formulation immediately after waking up in the morning. This review also explains the immunological factors which may trigger rheumatoid arthritis in human beings. It further explores conventional approaches like pH-dependant, microorganisms-driven, pressure-controlled, and time-dependant formulations. By employing two or more conventional approaches given above the various novel approaches have been designed to eliminate the drawbacks of individual techniques. [ABSTRACT FROM AUTHOR]

Background: Circadian rhythms is a natural process that regulates the sleep wake cycle which is associated with several physiological, biochemical, endocrine, behavioural processes in humans and entrainment to light-dark cycle. The activity of Ramelteon is believed to contribute to its sleep-promoting properties and thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle. A tablet can be given before 2 hr of bed time, so the Ramelteon drug shows its effect throughout the night by releasing the active content with lag time followed by sustained action to promote the sleep. Materials and Methods: Chronotherapeutic drug delivery system were prepared by compression coating technology using pH independent, hydrophilic and hydrophobic polymers. Results: Drug excipient compatibility indicated that the Ramelteon Active pharmaceutical ingredient (API) is compatibility with the excipients proposed. The X-ray Diffraction (XRD) studies indicated that the crystalline form of the Ramelteon API existed in the finished formulation. Conclusion: The core tablets containing Eudragit RSPO 10mg/tablet and ratio of Ethyl cellulose: Hydroxy propyl methyl cellulose (HPMC) of 70:30 in the outer coating material yielded a desired lag time of 2 hr and drug release for a period of 4 hr to achieve a chronotherapeutic drug delivery system. Ramelteon is an excellent candidate in designing chronotherapeutic drug delivery systems and further in vivo studies can be explored in the treatment of circadian rhythm with sleep wake cycle disorders. [ABSTRACT FROM AUTHOR]

An ideal colon specific drug delivery system needs to perform multiple functions like greater bio availability, less toxicity and higher therapeutic efficacy, all of which require high degree of smartness. This article focuses on the overview of the stimuli-responsive polymers and various nanodrug delivery systems which have found applications in colon specific delivery of drugs as this system provide a link between therapeutic need and drug delivery. These polymers exhibit a non-linear response to a small stimulus leading to a macroscopic alteration in their structure/properties. Stimuli responsive polymers display a significant physio chemical change in response to small changes in their environment (temperature, pH, light etc.). Colonic drug delivery has gained increased importance in treating diseases like Crohn’s disease, ulcerative colitis, colon cancer etc. The expansion in the development of polymers based system with greater flexibility, versatility and unexplored potential enables new opportunities for them in uplifting bio medicine. Applying the concepts of smartness in the context of clinically relevant therapeutic and diagnostic systems, it can prelude in a new era of ‘smart’ therapeutics that can improve the health care fields. In particular, due to its high sensitivity to the stimuli, this system has been identified as a sensible platform for releasing drug at suitable site and at appropriate time. [ABSTRACT FROM AUTHOR]

Polyvinylpyrrolidone includes soluble and insoluble grades; soluble grades are synthesised by the mechanism of polymerization, the free radical polymerization into the water by using hydrogen peroxide as an initiator, the mechanism which terminates the polymerisation reaction makes it probable to produce soluble polyvinylpyrrolidone of about any molecular weight. Cross-linked polymer shows yield through popcorn polymerisation of an N-vinylpyrrolidone which gets insoluble polyvinylpyrrolidone. Kollidon is in the market as a brand name for polyvinylpyrrolidone, a kollidon family now is a set of common excipients based on polyvinylpyrrolidone for use in the pharmaceutical industry. They have a great variety of applications in an oral formulation; the functions of oral formulation encompass fast disintegration, sustain drug release, solubility, bioavailability enhancement, and stabilize the active ingredient. Kollidon containing a mixture of polyvinyl acetate plus povidone are generally used in the formation of sustained release formulation. Owing to their high molecular weight, are recognized as a suitable vehicle for producing sustained release drug delivery system. In this review paper, applications of different grades of kollidon are organized in the form of tables and reviewed critically. Current literature of patents on kollidon based formulations is also presented. [ABSTRACT FROM AUTHOR]

The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (∼25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580–720 µm were obtained. Drug entrapment efficiency of ∼75–100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3–9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. Thein vivostudy revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ∼168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present investigation was to develop systematically optimized multiunit formulation for colon targeted delivery of metronidazole (MTZ) by employing design of experiment (DoE) and evaluate it forin vitroas well asin vivodrug release study. Methods: Core of mini-tablets of MTZ was prepared using drug along with suitable swelling agents to provide pH sensitive pulsatile drug delivery. Eudragit® S 100 (ES) and ethyl cellulose (EC) were used as coating polymers to prevent initial drug release in gastric region. The coating composition was systematically optimized using 32-full factorial design and optimized formulation was evaluatedin vitroand thenin vivo, to confirm colon targeting ability of the developed system. Stability study of optimized formulation was performed for 6 months as per ICH guidelines. Results: The optimized coating composition was selected from the results of design batches. The optimized formulation showed 6.99 ± 1.5% drug release up to 5 h and 100% drug release within 7.2 ± 0.2 h indicating pH sensitive pulsatile behavior of formulation. Similar drug release profile was observed while performingin vivostudy in rabbits with a lag time of 4 h andCmaxof 190 ± 4.9 ng/ml being achieved after 7 h. Stability study indicated insignificant difference in properties of tablets and their drug release patterns. Conclusion: Optimization of coating composition (EC and ES) and thickness could offer pH sensitive pulsatile release of drugs at colon. Furthermore,in vivoresults confirmed the successful development of colon targeted formulation of MTZ. [ABSTRACT FROM AUTHOR]

Context: In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose. Objective: The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration. Methods: Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studiedin vitroandin vivofor the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration. Results and conclusion: The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed. [ABSTRACT FROM AUTHOR]

Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. [ABSTRACT FROM AUTHOR]

The objective of this study is to develop and evaluate gastroretentive particulate delivery systems using Riboflavin-5′-monophosphate sodium salt dihydrate (RF5′PNa) as model drug. Poly(acrylic acid)-cysteine and chitosan-4-thiobuthylamidine were evaluated and compared as anionic and cationic polymers for gastroretentive particles. Permeation studies were performed with freshly excised stomach mucosa from rats. Polymers and combination with glutathione were evaluated for permeation enhancing properties. Furthermore, particles were prepared by air jet milling and characterized. Permeation studies showed that the apparent permeability coefficients for RF5′PNa with thiomers and glutathione are 1.511-fold and 2.354-fold higher than control, respectively. It can be seen from the results glutathione in combination with thiomers has a significant influence for increasing permeation. Poly(acrylic acid)-cysteine and chitosan-4-thiobuthylamidine particles demonstrated a mean diameter of 336.5 ± 16.5 and 396.3 ± 17.0 nm and zeta potential of −19.98 ± 1.015 and 27.15 ± 0.500 mV, respectively. The drug loading of Poly(acrylic acid) particles was significantly higher than chitosan particles. The release rate of RF5′PNa from the thiolated particles was slower compared with unmodified particles. Moreover, thiolated particles showed higher mucoadhesive properties compared to unmodified particles. Overall, thiolated particles of both anionic and cationic polymers had improved mucoadhesive and controlled release properties. Therefore, they could be promising for gastroretentive delivery systems. [ABSTRACT FROM AUTHOR]

A list of article related to drug delivery systems that were published in several journals in presented including "Advanced drug delivery systems that target the vascular endothelium," by B. S. Ding, T. Dziubla, V. V. Shuvaev, S. Muro and V. R. Muzykantov and "Antiangiogenesis and drug delivery to tumors: Bench to bedside and back," by D. G. Duda.