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Oral colon delivery has widely been pursued exploiting naturally occurring polysaccharides degraded by the resident microbiota. However, their hydrophilicity may hinder the targeting performance. The aim of the present study was to manufacture and evaluate a double-coated delivery system leveraging intestinal microbiota, pH, and transit time for reliable colonic release. This system comprised a tablet core, a hydroxypropyl methylcellulose (HPMC) inner layer and an outer coating based on Eudragit ® S and guar gum. The tablets were loaded with paracetamol, selected as a tracer drug because of the well-known analytical profile and lack of major effects on bacterial viability. The HPMC and Eudragit ® S layers were applied by film-coating. Tested for in vitro release, the double-coated systems showed gastroresistance in 0.1 N HCl followed by lag phases of consistent duration in phosphate buffer pH 7.4, imparted by the HPMC layer and synergistically extended by the Eudragit ® S/guar gum one. In simulated colonic fluid with fecal bacteria from an inflammatory bowel disease patient, release was faster than in the presence of β-mannanase and in control culture medium. The bacteria-containing fluid was obtained by an experimental procedure making multiple tests possible from a single sampling and processing run. Thus, the study conducted proved the feasibility of the delivery system and ability of guar gum to trigger release in the presence of colon bacteria without impairing the barrier properties of the coating. Finally, it allowed an advantageous simulated colonic fluid preparation procedure to be set up, reducing the time, costs, and complexity of testing and enhancing replicability., (© 2023. Controlled Release Society.)

A multiple-unit formulation for time-dependent colonic release of insulin was obtained by coating insulin and sodium glycocholate immediate-release minitablets with: (i) Methocel® E50, a low-viscosity hydroxypropyl methylcellulose (inner coating), (ii) 5:1 w/w Eudragit® NE/Explotab® V17, a mixture of a neutral polymethacrylate with a pore-forming superdisintegrant (intermediate coating), and (iii) Aqoat® AS, enteric-soluble hydroxypropyl methylcellulose acetate succinate (outer coating). Sodium glycocholate was added as a permeation enhancer while the inner, intermediate and outer coatings were aimed, respectively, at delaying the onset of release through swelling/erosion processes, extending the duration of the lag phase by slowing down water penetration into the underlying functional layer, and overcoming variable gastric residence time. In vitro studies showed that neither insulin nor sodium glycocholate were released from the three-layer system during 2h of testing in 0.1N HCl, while complete release of the protein and of the enhancer occurred in phosphate buffer, pH 6.8, after consistent lag phases. No significant changes were noticed in the release profiles following twelve-month storage at 4°C. Oral administration of the novel formulation to diabetic rats elicited a peak in the plasma insulin concentration after 6h, which was associated with a sharp decrease in the glycemic levels. The relative bioavailability and pharmacological availability of such a formulation, as determined vs. the uncoated tablets, were 2.2 and 10.3, respectively. Based on these results, the three-layer system presented was considered a potentially interesting tool for oral colonic delivery of insulin and adjuvant compounds., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this study, insulin-containing nanoparticles were loaded into pellet cores and orally administered to diabetic rats. Polyethylene imine-based nanoparticles, either placebo or loaded with insulin, were incorporated by extrusion and spheronization technology into cores that were subsequently coated with three overlapping layers and a gastroresistant film. The starting and coated systems were evaluated in vitro for their physico-technololgical characteristics, as well as disintegration and release performance. Nanoparticles-loaded cores showed homogeneous particle size distribution and shape. When a superdisintegrant and a soluble diluent were included in the composition enhanced disintegration and release performance were observed. The selected formulations, coated either with enteric or three-layer films, showed gastroresistant and release delayed behavior in vitro, respectively. The most promising formulations were finally tested for their hypoglycemic effect in diabetic rats. Only the nanoformulations loaded into the three-layer pellets were able to induce a significant hypoglycemic activity in diabetic rats. Our results suggest that this efficient activity could be attributed to a retarded release of insulin into the distal intestine, characterized by relatively low proteolytic activity and optimal absorption., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The exploitation of hot-melt extrusion and injection molding for the manufacturing of immediate-release (IR) tablets was preliminarily investigated in view of their special suitability for continuous manufacturing, which represents a current goal of pharmaceutical production because of its possible advantages in terms of improved sustainability. Tablet-forming agents were initially screened based on processability by single-screw extruder and micromolding machine as well as disintegration/dissolution behavior of extruded/molded prototypes. Various polymers, such as low-viscosity hydroxypropylcellulose, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, various sodium starch glycolate grades (e.g., Explotab(®) CLV) that could be processed with no need for technological aids, except for a plasticizer, were identified. Furthermore, the feasibility of both extruded and molded IR tablets from low-viscosity hydroxypropylcellulose or Explotab(®) CLV was assessed. Explotab(®) CLV, in particular, showed thermoplastic properties and a very good aptitude as a tablet-forming agent, starting from which disintegrating tablets were successfully obtained by either techniques. Prototypes containing a poorly soluble model drug (furosemide), based on both a simple formulation (Explotab(®) CLV and water/glycerol as plasticizers) and formulations including dissolution/disintegration adjuvants (soluble and effervescent excipients) were shown to fulfill the USP 37 dissolution requirements for furosemide tablets., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

This study is focused to design a colon specific pellet formulation of rifaximin based on the combination of time-dependent and pH sensitive delivery system using Quality-by-Design (QbD) approach for better and promising treatment of inflammatory bowel disease (IBD). An extrusion/spheronization process was utilized for the preparation of core macroparticles using ethyl cellulose (EC) as matrix former and microcrystalline cellulose (MCC) as a spheronizing aid. Two critical process parameters (CPPs) i.e., spheronization time and spheronizer speed were taken as independent factors while aspect ratio, sphericity, carr's index, and particle size were taken as dependent responses to optimize the composition of the core macroparticles. To regulate the drug release, core macroparticles were coated with Eudragit NE40D and Eudragit FS30D to impart time-dependent and pH sensitive release of drug. The optimized coated macroparticles were characterized for drug content and in vitrodrug release in different pH media of stomach and intestine. The coating levels of the inner and outer polymers were further optimized for the time required for 10 %, 50 % and 90 % drug release. The result showed that the 90% of drug of P3 and P4 formulation were found to be released in 10.87 and 13.19hrs respectively. When exposed to Scanning Electron Microscopy the images of coated macroparticles suggested a uniform and smooth coat of polymers over the surface of macroparticles. This formulation reduces the dose and the side effects due to its specific targeting at the site of inflammation makes it a better choice over the tablets. The result indicates that the developed formulation may possibly reduce the dosing frequency and side effects associated with the conventional tablet formulation for the site-specific targeting at inflammation site. [ABSTRACT FROM AUTHOR]

To prepare swellable/erodible time-dependent colon delivery systems with improved efficiency in delaying drug release, the application of an outer Eudragit® NE film, which contained the superdisintegrant Explotab® V17 as a pore former, was attempted. Tablet cores were successively spray-coated with a hydroxypropyl methylcellulose (HPMC) solution and diluted Eudragit® NE 30 D, wherein fixed amounts of Explotab® V17 were present. The resulting two-layer systems yielded lag phases of extended duration as compared with formulations provided with the HPMC layer only. By raising the thickness of the outer film, longer lag times were generally observed, whereas the effectiveness in deferring the drug liberation was reduced by increasing the pore former content, which, however, also resulted in a lower data variability. The films containing 20% of Explotab® V17 effectively and consistently prolonged the in vitro lag phase imparted by HPMC as a function of their thickness. Stored for 3 years under ambient conditions, a two-layer system with this outer film composition pointed out unmodified release patterns. The same system proved to meet gastroresistance criteria when enteric coated. The results obtained indicated that the proposed strategy would enable the preparation of erodible delivery systems with reduced size, possibly suitable as multiple-unit dosage forms., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)

The aim of the work was to explore the potential of hot-melt extrusion (HME) for preparing hydroxypropyl cellulose (HPC)-based prolonged-release matrices intended for oral administration. For this purpose, compressed and extruded systems, either composed of polymer only or containing different amounts of a model drug (theophylline or ketoprofen), were compared. The overall morphological/physical changes of the systems following interaction with water indicated that the manufacturing process would not exert a major influence on the swelling behavior of the polymeric matrices. On the other hand, the release rate was generally higher from HME systems probably due to an increase of the drug dissolution rate, which is in agreement with the relevant DSC data (loss of drug cristallinity). However, the technological characteristics of the matrices and the maximum drug load were demonstrated to depend on the mode of interaction of the active ingredient with the molten polymer. In this respect, the formation of a composite material from ketoprofen and HPC, when mixed in specific ratios, was supposed to explain the differences observed between compressed and extruded systems in terms of morphological characteristics, hydration/swelling and release. The obtained results support the possibility of exploiting the advantages offered by HME technique, above all the potential for continuous manufacturing, in the preparation of prolonged-release swellable matrices based on a cellulose derivative., (Copyright © 2013 Elsevier B.V. All rights reserved.)

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.)

In order to adapt a previously described swellable/erodible pulsatile delivery system to a multiple-unit configuration, insoluble films with adequate permeability and flexibility were proposed for application to its functional hydroxypropyl methylcellulose (HPMC) layer. By slowing down the penetration of water into the system, such films would be expected to improve the relevant effectiveness in delaying the onset of release without possibly impacting on the mechanism involved. Free films of Eudragit(®)NE containing differing amounts (10-20%) of a superdisintegrant, i.e. Explotab(®)V17, Ac-Di-Sol(®), Kollidon(®)CL or Kollidon(®)CL-M, were prepared by spraying technique and evaluated for hydration, permeability and tensile properties. The hydration and permeability characteristics were enhanced by the addition of the superdisintegrants, generally as a function of their concentration. Explotab(®)V17 was shown particularly useful to increase the film permeability. Moreover, it exerted a minor impact on the advantageous tensile properties of the acrylic polymer, especially in the wet state. Based on these results and on a preliminary release study performed with two-layer devices, the Eudragit(®)NE film with Explotab(®)V17 at the highest investigated percentage was identified as a potential formulation candidate for being applied to HPMC-coated cores thus allowing the onset of release to effectively be delayed by coatings of reduced thickness., (Copyright © 2012 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.)

The aim of this work was to prepare and evaluate an oral dosage form intended for time-dependent colon delivery of insulin along with a selected protease inhibitor (camostat mesilate) and absorption enhancer (sodium glycocholate). A previously described release platform, which had proven potentially suitable for the protein delivery, was exploited. Insulin compatibility with the above-mentioned adjuvants was preliminarily evaluated. For this purpose, the drug and its main degradation products were assayed by HPLC in insulin powder mixtures with camostat mesilate and/or sodium glycocholate stored 12 months at 4 degrees C. No significant decrease in protein content or increase in degradation product percentages beyond Eur. Ph. 6th Ed. limits was highlighted. Moreover, calorimetric studies performed on physical and compacted binary insulin mixtures with camostat mesilate and sodium glycocholate showed that the thermal behavior of both adjuvants was unchanged. Subsequently, tablet cores with differing compositions were prepared and spray-coated with an aqueous HPMC solution in order to obtain pulsatile delivery systems. The coated units were demonstrated to concurrently release the drug and the adjuvants in a prompt and quantitative mode after consistent lag times. Based on these results, the device was proven a potential candidate for colon delivery of insulin and the selected adjuvants., (2009 Wiley-Liss, Inc. and the American Pharmacists Association)

The aim of the present work was to evaluate the viability of a time-dependent delivery platform (Chronotopic) in preparing an insulin-based system intended for oral colon delivery. The main objectives were to assess the influence of the manufacturing process and storage conditions on the protein stability. Insulin-loaded cores were manufactured by direct compression and were subsequently coated with hydroxypropyl methylcellulose (HPMC) in a top-spray fluid bed up to increasing weight gains, namely 20%, 60% and 100%. In order to evaluate the impact the operating conditions may have on the protein integrity, insulin and its main degradation products (A21-desamido insulin -A21, Other Insulin-Related Compounds -OIRCs, and High-Molecular Weight Proteins -HMWPs) were assayed on samples collected after each process step by chromatographic methods. Furthermore, long-term (4 degrees C) and accelerated (25 degrees C-60% RH) stability studies were carried out on tablet cores and coated systems by assessing insulin, A21, OIRC and HMWP percentages throughout a one-year storage period. In addition, the in vitro release behaviour was investigated during the same study period. The overall results indicated that the manufacturing process is not detrimental for insulin integrity and that 4 degrees C storage temperature alters neither the protein content nor the release performances of the device. It was therefore concluded that insulin-containing systems intended for oral colon delivery can be obtained by the Chronotopic technology.

The purpose of the present study was to investigate the permeation characteristics of the beta sheet breaker peptide AS 602704 (BSB) on excised bovine nasal mucosa using an Ussing chamber model. The influence of various absorption enhancers such as sodium cholate, sodium dodecyl sulfate (SDS), cetrimidum, sodium caprate, Na(2)EDTA, polycarbophil (PCP), the thiomer conjugate polycarbophil-cysteine (PCP-Cys), and poly-l-arginine (poly-l-arg; 100 kDa) was evaluated. Additionally, the influence of temperature and pH on the transport rate as well as the stability of the peptide drug against enzymatic degradation were investigated in vitro. The effective permeability coefficient (P(eff)) of BSB in Krebs-Ringer-buffer (KRB) pH 7.4 was (1.89 +/- 0.44)* 10-5, while in the presence of sodium caprate (0.5%) a P(eff) of (9.58 +/- 1.82)*10-5 was achieved. Rank order of enhancement ratio was sodium caprate > SDS > sodium cholate > Na(2)EDTA > poly-L-arg = PCP-Cys. In case of cetrimidum and PCP even a decrease in the absorption of BSB was determined. Na2EDTA reduced the enzymatic degradation of BSB when exposed to a nasal tissue homogenate by more than the half. An increased lipophilicity of BSB because of a more acidic milieu (pH 5.5) did not lead to an increased transcellular transport. Permeation studies carried out at 4 degrees C compared to 37 degrees C demonstrated a temperature dependent permeation behaviour suggesting an additional active carrier mediated transport. The results obtained within these studies should facilitate the development of a nasal delivery system for AS 602704 for the treatment of Alzheimer's disease.

It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

Lipid microparticles (LMs) as a sustained release system for a gonadotropin release hormone (GnRH) antagonist (Antide) were prepared and evaluated. Antide loaded microparticles (Antide-LMs) were obtained by a cryogenic micronization process starting from two different monoglycerides (glyceryl monobehenate and glyceryl monostearate) and using two different incorporation methods (co-melting and solvent evaporation). Antide-LMs, 2% (w/w) loading, were characterized for drug incorporation by RP-HPLC, particle size by laser diffractometry and surface morphology by scanning electron microscopy. In vitro peptide release and in vitro biological activity were also studied. Serum Antide and testosterone levels, as pharmacodynamic marker, were assessed following subcutaneous administration in rats. Antide-LMs showed a mean diameter of approximately 30 micro m and variable Antide release depending on lipid matrix and incorporation method. In vivo experiments demonstrated that detectable Antide plasma levels were present, in the case of Antide-LMs based on Compritol E ATO obtained by co-melting procedure, for at least 30 days after dosing. Testosterone levels were consistent with prolonged pharmacokinetic profiles. In vitro release of Antide from LMs correlated well with the in vivo release. In conclusion, LMs can sustain the release of Antide for at least 1 month. The levels of the initial 'burst' and the extent of the pharmacodynamic effect can be influenced by the lipid characteristics and by process conditions.

Antide is a decapeptide [(N-Ac-D-Nal(1)-D-Cpa(2)-D-Pal(3)-Ser(4)-Lys(Nic)(5)-D-Lys(Nic)(6)-Leu(7)-Ilys(8)-Pro(9)-D-Ala(10)-NH(2)] that acts in vivo as an antagonist of GnRH (gonadotropin-releasing hormone). The conformational behavior of antide has been studied in water, TFE, DMF, and DMSO solutions by means of 2D-NMR spectroscopy and molecular dynamics calculations. Antide adopts in aqueous solution a delta-shaped backbone conformation, which is characterized by an irregular turn around residues D-Pal(3)-Ser(4) and by the close spatial proximity of the side chains belonging to D-Nal(1) and Ilys(8) (as many as 17 NOE peaks were detected between these side chains). The side-chain protons of Ilys(8) (especially the H(gamma) ones) present remarkably upfield shifted resonances, because of ring current effects induced by the naphthyl moiety. The upfield shifted resonances of the Ilys(8) H(gamma) hydrogen atoms are strictly characteristic of the water delta-shaped conformation and can be considered as structure markers. The observation of ring current shifted Ilys(8) H(gamma) resonances under different conditions (temperature, pH, solvent) indicates a remarkable stability of the water delta-shaped conformation. Such a conformation is at least partially disrupted in solvent mixtures containing high percentages of organic solvents. TFE can induce a well-defined conformation, which is characterized by an S-shaped backbone conformation. In DMF and DMSO solution, the molecule is basically endowed with a random coil conformation and high fluxionality. Antide fulfills the conformational requirements that are known to play a crucial role in receptor recognition, namely (i) the presence of a turn in the backbone and (ii) the all-trans nature of peptide bonds. In addition, the structural rigidity of antide likely adds a further contribution to the receptor binding affinity.

Changes in the homeostasis of blood sugar levels are a hallmark of diabetes mellitus, an incurable metabolic condition, for which the first-line treatment is the subcutaneous injection of insulin. However, this method of administration is linked to low patient compliance because of the possibility of local infection, discomfort and pain. To enable the administration of the peptide through more palatable paths without requiring an injection, like by oral routes, the use of nanoparticles as insulin carriers has been suggested. The use of nanoparticles usually improves the bioavailability and physicochemical stability of the loaded medicine. The utilisation of several forms of nanoparticles (like lipid and polymeric nanoparticles, micelles, dendrimers, liposomes, niosomes, nanoemulsions and drug nanosuspensions) is discussed in this article as a way to improve the administration of various oral hypoglycaemic medications when compared to conventional treatments. [ABSTRACT FROM AUTHOR]

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]

Colon targeted drug delivery devices have attracted a lot of attention since they may be employed often to treat colonic illnesses locally with fewer harmful effects on the body and improve oral administration of several medicines that are vulnerable to enzymatic and acidic degradation in the gastrointestinal tract . The rising need for a more patient friendly drug administration system and the recent expansion of the global pharmaceutical market for biologics both highlight the value of colonic drug delivery as a non invasive delivery method for macro-molecules Given that they are painless and self-administrable, Colon targeted drug delivery system (CTDDS) for macromolecules have therapeutic advantages including increased patient compliance and lower costs. Numerous approaches have been researched, including pH dependent system enzyme triggered system receptor medicated system, and magnetically driven system, to give more effective colonic drug administration for local or systemic drugs. This paper highlights recent improvements in a number of methods for creating CTDDS and their medicinal uses, with a focus on formulation technology. New types of polymeric system are being developed for the treatment of colon diseases on the theory of site-specific drug release based on diverse mechanisms. To go to the colon successfully, a drug must first be shielded drug degradation release and absorption in the upper gastro intestinal tract (G.I.T.), then released gradually or instantly in the proximal colon . The purpose of this study is to discuss existing methodologies and new developments in dosage forms that target the colon. [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]

The aim of this study was to investigate the feasibility of concentrated natural rubber latex (CNRL), a major polymer, blended with either hydroxypropylmethylcellulose (HPMC) or ethylcellulose (EC) for film coated tablets. Propranolol hydrochloride tablets were used as core materials for coating. The blended films were preliminary casted and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and scanning electron microscopy (SEM) techniques. The in vitro drug releases of film coated tablets were evaluated and their results fitted to zero, first, and Higuchi's kinetic models to investigate the mechanism of drug released. The results showed that CNRL–HPMC and CNRL–EC blended films did not change in DSC, XRD, and SEM results from their raw properties. CNRL–HPMC and CNRL–EC could form the coated films on the tablets completely, and the in vitro drug release data showed the retardation effect of drug release in all formulations. The drug releases from 5%CNRL–1, 2, or 5%HPMC, and 5%CNRL–5%EC film coated tablets fitted to Higuchi's model, and those from 5%CNRL–1 or 2%EC film coated tablets fitted to first order kinetics. HPMC and EC amounts also affected the properties of film coated tablets. Increasing the HPMC amount in the coating dispersion provided the increase of release rate of drug. On the other hand, increasing amount of EC, the release rate decreased. SEM photographs showed the thickness of coated film on core tablets that depended on amount of coating levels. Thus, this work successfully used CNRL blending as film forming agent in tablet coating. The results confirmed that CNRL blends were possible to be used as film former for pharmaceutical coating applications. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to develop a method for the preparation and characterization of paroxetine (PRX) tablets, obtained by coupling hot-melt extrusion and fused deposition modelling (FDM)-based three-dimensional printing (3DP) technology. The impact of the printing process parameters on the drug stability and on the tablets performance was assessed. Methods: Tablets were obtained by FDM of hot-melt extruded PRX-loaded filaments. Physicochemical, thermal, spectroscopic, diffractometric analysis and in-vitro dissolution tests of the intermediate products and the finished dosage forms were performed. Key findings: The characterization of printed tablets evidenced mass and dimensions uniformity, and consistency of drug content and dissolution profile. The formation of amorphous solid dispersions and interaction of formulation components throughout the manufacturing process were demonstrated. Layer thickness, printing temperature, printing and travelling speeds, and infill were the most impacting process parameters on both the physicochemical properties and the in-vitro performance of the 3D-printed tablets. Conclusions: PRX tablets, meeting compendial limits, were manufactured by 3DP, envisaging their clinical use as individually designed dosage forms. The assessment of the impact of processing parameters on the printed tablets provided insights, which will ultimately allow streamlining of the 3D process set-up for quicker and easier production of patient-centric medicines. [ABSTRACT FROM AUTHOR]

Oral administration of insulin is one of the most challenging topics within this area, because insulin is degraded in stomach before it enters the bloodstream. In this study, for the first time, a nano‐carrier for controlled and targeted oral delivery of insulin was developed using de‐esterified Tragacanth and chitosan. The fabricated nanoparticles were synthesized using coacervation technique and their properties were optimized using response surface methodology. The effect of experimental variables on the particle size and loading efficiency was examined. In addition, the interactions between components were analyzed using Fourier transform infrared. The thermal stability of nanoparticles was studied by thermal gravimetric analysis. The insulin loading efficiency was measured and in vitro release profile and ex vivo insulin permeability was determined. Optimized nanoparticles showed spherical shape with a size less than 200 nm and zeta potential of +17 mV. Owing to their nanoscale dimensions and mucoadhesiveness, nanoparticles were synthesized using medium molecular weight of Chitosan. The insulin loading efficacy for the system was 6.4%, released under simulated gastrointestinal conditions in a pH‐dependent manner. Based on all of the obtained results, it can be concluded that these nanoparticles can potentially be utilized as a carrier for the oral insulin delivery. [ABSTRACT FROM AUTHOR]

Hot-melt extrusion has found extensive application as a feasible pharmaceutical technological option over recent years. HME applications include solubility enhancement, taste masking, and sustained drug release. As bioavailability enhancement is a hot topic of today's science, one of the main applications of HME is centered on amorphous solid dispersions. This review describes the most significant aspects of HME technology and its use to prepare solid dispersions as a drug formulation strategy to enhance the solubility of poorly soluble drugs. It also addresses molecular and thermodynamic features critical for the physicochemical properties of these systems, mainly in what concerns miscibility and physical stability. Moreover, the importance of applying the Quality by Design philosophy in drug development is also discussed, as well as process analytical technologies in pharmaceutical HME monitoring, under the current standards of product development and regulatory guidance. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) has been endemic in Italy since 2013. In a multicenter cohort study, we investigated various aspects of KPC-Kp among patients, including 15-day mortality rates and delays in adequate therapy. Most (77%) KPC-Kp strains were sequence types ST512 or ST307. During 2017, KPC-Kp prevalence was 3.26 cases/1,000 hospitalized patients. Cumulative incidence of KPC-Kp acquired >48 hours after hospital admission was 0.68% but varied widely between centers. Among patients with mild infections and noninfected colonized patients, 15-day mortality rates were comparable, but rates were much higher among patients with severe infections. Delays of >4 days in receiving adequate therapy more frequently occurred among patients with mild infections than those with severe infections, and delays were less common for patients with known previous KPC-Kp colonization. Italy urgently needs a concerted surveillance system to control the spread of KPC-Kp. [ABSTRACT FROM AUTHOR]

The development of orally administered protein drugs is challenging due to their intrinsic unfavourable features, including large molecular size and poor chemical stability, both of which limit gastrointestinal (GI) absorption efficiency. Nanoparticles can overcome the GI barriers effectively and improve the oral bioavailability of proteins in the GI tract. They possess large surface area to volume ratio, and can facilitate the GI absorption of nanoparticles via the paracellular and transcellular routes. Nanoparticles can be prepared by various fabrication techniques that can encapsulate the fragile therapeutic proteins via hydrophobic bonding and electrostatic interaction. A desirable technique should involve minimal harsh conditions and encapsulate therapeutic proteins with preserved functionalities. The current review examines the characteristics of each preparation technique, and illustrates the examples of insulin-loaded nanoparticles that have been developed in each fabrication method. The following techniques, which include nanoprecipitation, hydrophobic conjugation, flash nanocomplexation, double emulsion, ionotropic gelation, and layer-by-layer adsorption, have been used to formulate ligand-modified nanoparticles for targeted delivery of insulin. Other techniques, including reduction, complex coacervation (polyelectrolyte complexation), hydrophobic ion pairing and emulsion solvent diffusion method, and sol-gel technology, were also discussed in the latter part of the review due to their extensive use in fabrication of insulin nanoparticles. This review also discusses the strategies that have been utilised during the formulation process to improve the stability and bioactivity of therapeutic proteins. [ABSTRACT FROM AUTHOR]

Oral delivery of insulin-loaded therapeutics is challenging due to the extreme pH condition, enzymatic degradation, and limited permeation in the gastrointestinal (GI) tract. Nanoparticles can overcome various GI barriers and improve the oral bioavailability of insulin. Although a number of novel strategies have been reported to optimise the orally administered nano-formulation, its clinical translation remains unachievable. Animal studies are essential to establish the protective effect, transit behaviour, retention time, mucoadhesiveness degree, absorption mechanism and distribution of nanoparticle in the GI tract. In this review, we examine various instrumentations, such as Ussing chamber, fluorescence microscope, TEM, CLSM, that are available for investigating the ex vivo intestinal absorption and mucoadhesive capability of insulin-loaded nanoparticles. More importantly, a comprehensive understanding and evaluation of in vivo animal studies are crucial to clarify the physiological properties of insulin nanoparticles. In addition, the biocompatibility of nanoparticle is a critical prerequisite for short-term and long-term use of drug formulation. The success of oral nanomedicine should improve the bioavailability of insulin and elicit no damage to internal organs. Lastly, we reviewed the current status of animal assays, including mucoadhesiveness study, biocompatibility (integrity of intestinal mucosa, histological analysis, oxidative stress, physical symptoms), biodistribution (fluorescence imaging, SPECT) and in vivo efficacy study, for the evaluation of orally administered insulin-loaded nanoparticles in pre-clinical stage. [ABSTRACT FROM AUTHOR]

Background: The Cucurbitaceae family has been known for its presence of phytoconstituents, namely, lupeol, β-sitosterol, terpenoids, phenols, and proteins with therapeutic potential. Objectives: The research paper tries to focus on major therapeutic field of people demographic area of type of cancer. Soxhlet extraction of Benincasa hispida (BH) was carried out and crude extract was converted to powder. Niosomal gel was formulated after the optimization of drug concentration from the extract of Niosomal solution. Solution with maximum entrapment was selected for the preparation of gel. Gel was prepared by using different Carbopol grades and with comparison of different parameters. Gel was studied for gas chromatography-high-resolution mass spectrometry (GC-HRMS) evaluation for check toxicity. Biologic activity was analyzed by SRB (Sulforhodamine B) assay with in vitro cell lines (human oral cancer cell line KB and Mus Musculus skin melanoma B16-F10). Results: Solution which was clear and white was selected for gel development. Carbopol 934 (1') as gelling agent showed good formulation properties. It was non-gritty, easily spreadable, and washable. The gel with maximum entrapment efficiency was evaluated further. GC-HRMS revealed 1.2-ethyl 2-Hexen-1-ol; 1,8-(3-Octyl-2-oxiranyl)-1-octanol; Dodecanoic acid, 2-penten-1-yl ester; Cholestane, 4, 5-epoxy-,(4α,5α); Cyclopentaneundecanoic acid; 17-octadecynoic acid; Octadecanoic acid, methyl ester; Methyl oleate; Tridecanoic acid, methyl ester; and Silane, dimethyl (2,3,6, tricholrophenoxy) heptadicycloxy. The selected cell lines did not show satisfactory activity at different concentrations in SRB assay. Conclusion: This research paper tried to witness the probable potential of BH for cancer with analytical base. Future studies may be undertaken at various stages and levels to further explore the potential of these families of plants. [ABSTRACT FROM AUTHOR]

Therapeutic peptides are administered via parenteral route due to poor absorption in the gastrointestinal (GI) tract, instability in gastric acid, and GI enzymes. Polymeric drug delivery systems have achieved significant interest in pharmaceutical research due to its feasibility in protecting proteins, tissue targeting, and controlled drug release pattern. In this study, the size, polydispersity index, and zeta potential of insulin-loaded nanoparticles were characterized by dynamic light scattering and laser Doppler micro-electrophoresis. The main and interaction effects of chitosan concentration and Dz13Scr concentration on the physicochemical properties of the prepared insulin-loaded nanoparticles (size, polydispersity index, and zeta potential) were evaluated statistically using analysis of variance. A robust procedure of reversed-phase high-performance liquid chromatography was developed to quantify insulin release in simulated GI buffer. Results and discussion: We reported on the effect of two independent parameters, including polymer concentration and oligonucleotide concentration, on the physical characteristics of particles. Chitosan concentration was significant in predicting the size of insulin-loaded CS-Dz13Scr particles. In terms of zeta potential, both chitosan concentration and squared term of chitosan were significant factors that affect the surface charge of particles, which was attributed to the availability of positively-charged amino groups during interaction with negatively-charged Dz13Scr. The excipients used in this study could fabricate nanoparticles with negligible toxicity in GI cells and skeletal muscle cells. The developed formulation could conserve the physicochemical properties after being stored for 1 month at 4 °C. The obtained results revealed satisfactory results for insulin-loaded CS-Dz13Scr nanoparticles (159.3 nm, pdi 0.331, −1.08 mV). No such similar study has been reported to date to identify the main and interactive significance of the above parameters for the characterization of insulin-loaded polymeric-oligonucleotide nanoparticles. This research is of importance for the understanding and development of protein-loaded nanoparticles for oral delivery. [ABSTRACT FROM AUTHOR]

A swellable/erodible system for oral time-dependent release, demonstrated to provide consistent pulsatile and colonic delivery performance, has been manufactured through a range of coating techniques to achieve the functional hydroxypropyl methylcellulose (HPMC) layer. Although aqueous spray-coating has long been preferred, the processing times and yields still represent open issues, especially in view of the considerable amount of polymer required to give in vivo lag phases of proper duration. To make manufacturing of the delivery system more cost-efficient, different coating modes were thus evaluated, namely top and tangential spray-coating as well as powder-layering, using a fluid bed equipment. To this aim, disintegrating tablets of 5 mm in diameter, containing a tracer drug, were coated up to 50% weight gain with low-viscosity HPMC, either as a water solution or as a powder formulation. In all cases, process feasibility was assessed following setup of the operating conditions. Irrespective of the technique employed, the resulting dosage forms exhibited uniform coating layers able to defer the onset of release as a function of the amount of polymer applied. The structure and thickness of such layers differed depending on the deposition modes. With respect to top spray-, both tangential spray-coating and powder-layering were shown to remarkably ameliorate the process time, which was reduced to approximately 1/3 and 1/6, and to enhance the yield by almost 20 and 30%, respectively. Clear advantages associated with such techniques were thus highlighted, particularly with respect to powder-layering here newly proposed for application of a swellable hydrophilic cellulose derivative. [ABSTRACT FROM AUTHOR]

This study aimed to develop a ternary nanocomposite system of organoclay, glycol-chitosan, and Eudragit®S100 as an effective colon targeted drug delivery carrier to enhance the oral absorption of insulin. A nanocomplex of insulin and aminoclay was prepared via spontaneous co-assembly, which was then coated with glycol-chitosan and Eudragit S®100 (EGAC-Ins). The double coated nanocomplex, EGAC-Ins demonstrated a high entrapment efficiency of greater than 90% and a pH-dependent drug release. The conformational stability of insulin entrapped in EGAC-Ins was effectively maintained in the presence of proteolytic enzymes. When compared to a free insulin solution, EGAC-Ins enhanced drug permeability by approximately sevenfold in Caco-2 cells and enhanced colonic drug absorption in rats. Accordingly, oral EGAC-Ins significantly reduced blood glucose levels in diabetic rats while the hypoglycemic effect of an oral insulin solution was negligible. In conclusion, EGAC-Ins should be a promising colonic delivery system for improving the oral absorption of insulin. [ABSTRACT FROM AUTHOR]

Interpolyelectrolyte complexes or polyplexes can be seen as interesting alternatives in the purpose of active ingredients encapsulation. Working on polymethylmethacrylate derivatives with special focus on controlled oral drug delivery, the influence of charged polyelectrolytes (polyacrylic acid, polyethylenimine, and amino‐dextran) and noncharged ones (polyvinyl alcohol, dextran 40, and Pluronic F68) has been investigated on the precipitation of two pH‐sensitive Eudragit polymers, namely, L100 and E100. Moreover, the possibility of preparing polyplexes involving the two polymethylmethacrylate derivatives with different charged and noncharged secondary polyelectrolytes has been studied. The obtained dispersions have been characterized in terms of mean particle size, size distribution, zeta potential, and morphology. Direct precipitation of Eudragit L100 by medium acidification in a batch process and in the presence of polyethylenimine allowed the production of particles with a narrow size distribution. The mean size was around 200 nm. In this case, the zeta potential was found to be +45 mV at pH = 7 in 1mM aqueous NaCl solution, and the produced suspension was stable in time since no aggregation and sedimentation have been observed. A precipitation pH of 8.16 allows us to suggest the preparation of a polyplex based on Eudragit L100 and polyethylenimine. In contrary, polyvinyl alcohol has shown ability to induce an increase in particle mean size whereas other polyelectrolytes showed no significant effect. Moreover, it was observed that polyethylenimine and polyacrylic acid solutions were able to directly induce Eudragit E100 precipitation whereas amino‐dextran and noncharged polyelectrolytes showed no effect on its precipitation and on particle size distribution. [ABSTRACT FROM AUTHOR]

Objective: Drug release systems based on colonic microbiota have been explored with the use of polysaccharides, which are biodegradable. In order to modulate the release into the colon, dapsone tablets were developed, coated with Surelease® and chondroitin sulfate (SC). Methods: The formulation was developed using the wet granulation method, in the form of 9-millimetre circular tablets. The coating was applied in a perforated basin-type coating using different proportions of Surelease® and chondroitin sulfate. The tablets were assessed according to the criteria of mean weight, hardness, and friability. The dissolution test was performed in the dissolver IV apparatus, in media simulating the gastrointestinal system environments (pH 1.2–pH 6.0 and pH 7.2) for 420 min. The results were analyzed by statistical analysis and factorial design. Results: The results of mean weight, hardness, and friability met the pharmacopeial specifications. In the dissolution test, the results obtained demonstrated that Surelease® is able to offer effective protection to the drug, releasing minimum rates when used at 6% or 10% of the tablet's weight gain. The experiments showed that the drug was not able to spread through the coatings manufactured exclusively with Surelease® or even when SC was incorporated in different proportions. Only in the formulation where SC was included in the highest proportion (10%), and the weight gain of the tablet was lower (6%), the release of dapsone increased, reaching 9.5% of drug released. Through factorial planning, it was observed that the drug release rate increases when the weight gain of the tablet remains at the lower level (6%), while the amount of polysaccharide is increased (90:10). Conclusions: The data indicate that the proportion of polysaccharide for ethyl cellulose in the film and the thickness of the coating are the key parameters in controlling the release of the drug from the system. [ABSTRACT FROM AUTHOR]

In the study, we developed a novel oral dosage form of Compound Danshen to resolve the problems of low bioavailability, disequilibrium in drug release, and stomach degradation of active components of Compound Danshen in conventional formulas. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was prepared using a semipermeable shell with the core components. Using a single-factor method, we obtained the optimal formulation that consisted of Salvia miltiorrhiza extract, Panax notoginseng extract, Borneol, sodium chloride, polyethylene oxide wsr-N10, hydroxypropyl-β-cyclodextrin, and ludipress. Moreover, in vitro dissolution test showed simultaneous releases of active ingredients from Compound Danshen COPC over 12 h at pH 7.8, displaying zero-order release characteristics. The impetus of drug release mainly depended on the difference in osmotic pressure across the capsule shell. Next, scanning electron microscopy showed morphological changes in the capsule shell during the dissolution test. More importantly, pharmacokinetic study in beagle dogs indicated that relative bioavailability was 330.58% and retention time was greatly prolonged in Compound Danshen COPC, compared with those in marketed Compound Danshen tablet products. Finally, in vivo imaging studies in beagle dogs showed that COPC was stable in gastrointestinal tract and the drug was specifically released in the colon region. [ABSTRACT FROM AUTHOR]

Pectin-based hydrogel microcarriers have shown promise for drug delivery to the colonic region. Microcarriers must remain stable throughout the upper gastrointestinal tract for effective colonic delivery, an issue that traditional pectin-based microcarriers have faced. The positively-charged natural biopolymer oligochitosan and divalent cation Ca2+ were used to dually cross-link pectin-based hydrogel microcarriers to improve carrier stability through simulated gastric and intestinal environments. Microcarriers were characterized with Scanning Electron Microscope and Fourier-Transform Infrared analysis. An optical microscope was used to observe the change of microcarrier size and morphology over time in the simulated gastrointestinal environments. Fluorescently-labeled Dextran was used as a model drug for this system. Calcium-Oligochitosan-Pectin microcarriers exhibited relatively small drug release in the upper gastrointestinal regions and were responsive to the high pH and enzymatic activity of simulated colonic environment (over 94% release after 2 h), suggesting great potential for colonic drug delivery. [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]

Colon-specific drug delivery is critical for treating diseases of colon, such as colon cancer, amoebiasis, irritable bowel syndrome, and inflammatory bowel disease. This study reviews the effects of targeted oral drug delivery on patient by measuring the accurate administration of the drug to specific disease spot, thus enhancing the therapeutic efficacy and provides better therapeutic outcomes. Medically targeted delivery to colon produces local effect on the diseases and hinders the systemic toxic effects of drugs. The delivery of therapeutics to the specific diseased part of colon has its merits over systemic drug delivery, albeit has some obstacles and problems. Colon drug delivery can be used to create both systemic and local effects. Many advanced approaches are used, such as conventional methods for drug release to colon, delayed release dosage forms, nanoparticles, carbon nanotubes, dendrimers, and alginate coated microparticles. This concise review summarizes and elaborates the details of different techniques and strategies on targeted oral drug delivery to colon as well as studies the advantages, disadvantages, and limitations to improve the application of drug in the part of the affected colon. [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 current study reports on the manufacturing of extended release dosage forms of metoprolol succinate via hot-melt extrusion (HME) technology. Either Eudragit®S100 and Eudragit®L100 alone or in combination with release modifying agent Polyox™ WSR 303 and Eudragit®L100-55 were processed to obtain complete and faster release. Metoprolol succinate with similar solubility parameters to polymer was dispersed in polymer matrix and was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Stability of drug after extrusion was confirmed by thermogravimetric analysis and high-performance liquid chromatography. Physical characterization method exhibited that the drug was homogeneously dispersed in non-crystalline state in Eudragit®L100-55-based formulations whereas in semi-crystalline state in Polyox™ WSR 303. The drug release percentage was below 3 and 40% in 0.1 N HCL with Eudragit®L100-55- and Polyox™ WSR 303-containing formulations, respectively, and exhibited pH-dependent dissolution properties. The drug-release mechanism was anomalous with Polyox™ WSR 303 formulations whereas diffusion through pore formation was obtained with Eudragit®L100-55. Both Eudragit®L100-55 and Polyox™ WSR 303 changed the release mechanism and kinetics of drug release from thermally processed dosage forms. The optimized stable formulation is similar to the marketed formulation with F2 value of 72.36. Thus, it can be concluded that HME was exploited as an effective process for the preparation of controlled release matrix system based on pH-dependent polymer matrices Eudragit®S100 and Eudragit®L100. [ABSTRACT FROM AUTHOR]

Most of published reviews of twin-screw extrusion focused on its application for enhancing the bioavailability of amorphous solid dispersions while few of them focused on its use for manufacturing sustained-release oral dosage forms and medical implants, despite the considerable interest and success this process has garnered both in academia and in the pharmaceutical industry. Compared to conventional batch processing, twin-screw extrusion offers the advantages of continuous processing and the ability to prepare oral dosage forms and medical implants that have unique physicochemical and drug release attributes. This review provides an in-depth analysis of the formulation composition and processing conditions of twin-screw extrusion and how these factors affect the drug release properties of sustained-release dosage forms. This review also illustrates the unique advantages of this process by presenting case studies of a wide variety of commercial sustained-release products manufactured using twin-screw extrusion. [ABSTRACT FROM AUTHOR]

Nanotechnology has enabled the development of innovative technologies and products for several industrial sectors. Their unique physicochemical and size-dependent properties make the engineered nanomaterials (ENMs) superior for devising solutions for various research and development sectors, which are otherwise unachievable by their bulk forms. However, the remarkable advantages mediated by ENMs and their applications have also raised concerns regarding their possible toxicological impacts on human health. The actual issue stems from the absence of systematic data on ENM exposure-mediated health hazards. In this direction, a comprehensive exploration on the health-related consequences, especially with respect to endocrine disruption-related metabolic disorders, is largely lacking. The reasons for the rapid increase in diabetes and obesity in the modern world remain largely unclear, and epidemiological studies indicate that the increased presence of endocrine disrupting chemicals (EDCs) in the environment may influence the incidence of metabolic diseases. Functional similarities, such as mimicking natural hormonal actions, have been observed between the endocrine-disrupting chemicals (EDCs) and ENMs, which supports the view that different types of NMs may be capable of altering the physiological activity of the endocrine system. Disruption of the endocrine system leads to hormonal imbalance, which may influence the development and pathogenesis of metabolic disorders, particularly type 2 diabetes mellitus (T2DM). Evidence from many in vitro, in vivo and epidemiological studies, suggests that ENMs generally exert deleterious effects on the molecular/hormonal pathways and the organ systems involved in the pathogenesis of T2DM. However, the available data from several such studies are not congruent, especially because of discrepancies in study design, and therefore need to be carefully examined before drawing meaningful inferences. In this review, we discuss the outcomes of ENM exposure in correlation with the development of T2DM. In particular, the review focuses on the following sub-topics: (1) an overview of the sources of human exposure to NMs, (2) systems involved in the uptake of ENMs into human body, (3) endocrine disrupting engineered nanomaterials (EDENMs) and mechanisms underlying the pathogenesis of T2DM, (4) evidence of the role of EDENMs in the pathogenesis of T2DM from in vitro, in vivo and epidemiological studies, and (5) conclusions and perspectives. [ABSTRACT FROM AUTHOR]

Following recent advances in nutrigenomics and nutrigenetics, as well as in view of the increasing use of nutraceuticals in combination with drug treatments, considerable attention is being directed to the composition, bioefficacy, and release performance of dietary supplements. Moreover, the interest in the possibility of having such products tailored to meet specific needs is fast growing among costumers. To fulfill these emerging market trends, 3D-printed capsular devices originally intended for conveyance and administration of drugs were proposed for delivery of dietary supplements. Being composed of separate inner compartments, such a device could yield customized combinations of substances, relevant doses, and release kinetics. In particular, the aim of this work was to face early-stage industrial development of the processes involved in fabrication of nutraceutical capsules for oral pulsatile delivery. A pilot plant for extrusion of filaments based on pharmaceutical-grade polymers and intended for 3D printing was set up, and studies aimed at demonstrating feasibility of fused deposition modeling in 3D printing of capsule shells according to Current Good Manufacturing Practices for dietary supplements were undertaken. In this respect, the stability of the starting material after hot processing and of the resulting items was investigated, and compliance of elemental and microbiological contaminants, as well as of by-products, with internal specifications was assessed. Finally, operating charts highlighting critical process variables and parameters that would serve as indices of both intermediate and final product quality were developed. [ABSTRACT FROM AUTHOR]

Aims After oral administration, naproxen generates several side-effects related to stomach malfunction. Undoubtedly, the enteric dosage forms with naproxen can be considered as safer. Moreover, since it has been evidenced that development and growth of colorectal cancer is related to the presence of cyclooxygenase, naproxen is investigated in terms of the tumor prevention. The aim of the present work was to formulate and evaluate the properties of novel naproxen-loaded macrobeads, made on the basis of low-acyl gellan gum and its blends with carrageenans, guar gum, cellulose sulfate, and dextran sulfates. Method Seven formulations were prepared by ionotropic gelation. The morphology of the dried beads was evaluated by scanning electron microscopy. The next step focused on Raman spectroscopy and thermal analysis of naproxen, polymers, and the beads. Next, the swelling behavior was examined in three acceptor fluids at pH = 1.2; 4.5, and 7.4. The beads were evaluated regarding naproxen content and encapsulation efficiency. The last stage of the work concerned the drug release studies. Results Addition of any other polysaccharide than gellan resulted in flattening of the beads upon drying. Differential scanning calorimetry confirmed the crystalline form of naproxen. Raman spectra showed that no apparent interactions occurred. In the acidic environment, all the beads revealed the tendency to absorb water. The beads swelled to the greatest extent at pH = 4.5. Naproxen was released from the beads at a varied rate. At pH = 7.4, the most prolonged release was observed for the beads containing carrageenans. Conclusions We have proved that blending of gellan with various polysaccharides can change the pH-dependent properties of the beads loaded with naproxen. We believe that the information enclosed in the paper will be of particular importance regarding the development and characteristics of novel oral dosage forms based on natural polymers. [ABSTRACT FROM AUTHOR]