Polycarbophil Research Articles

Pilot Formulation Study of Ph-sensitive Gels

Abstract Drugs remain for a short time on mucus membranes, such as oral, ocular, or nasal mucus, which are washed with physiological fluids. One of the possibilities to overcome this obstacle is the application of solutions that, due to the physiological environment or stimulus, turn into more viscous gels. These gels often also have mucoadhesive properties and the drug is released from them for a longer period. Carbomer 940 (C940), polycarbophil (PCP), and chitosan (CH) are gel-forming excipients, and the consistency of their solutions changes due to the concentration of protons (pH); therefore, they are referred to as pH-sensitive gelling agents. The aim of this study was to prepare pH-sensitive solutions that form gels in the pH of the oral cavity. We prepared water solutions with various concentrations of gel-forming excipients and evaluated the appearance, pH of the solution, injectability of the solution, and pH of gelation. By determining the pH of gelation, suitable concentrations (w/w) of the used polymers were found, namely, 0.1% C940, 0.225% PCP, and 2.5% CH with medium molecular weight (CHM). The 0.1% C940 and 0.225% PCP solutions were injectable through the syringe with the smallest 0.5 mm needle diameter. The 2.5% CHM solution was not injectable even through the syringe with the largest 0.8 mm needle diameter. Solgels prepared at the determined concentrations were evaluated by a dissolution test in a pH 6.8 phosphate buffer using methylene blue (MB) as a model substance. After 60 min of dissolution, 77.04% ± 5.94%, 48.85% ± 5.74%, and 77.35% ± 4.98% of MB were released from samples with C940, PCP, and CHM, respectively. The dissolution of the C940 and CHM samples took place according to the Korsmeyer–Peppas kinetic model (R2 0.999 ± 0.001, 0.978 ± 0.003) and of the PCP samples took place according to the first-order model (R2 0.994 ± 0.001). The 0.225% PCP pH-sensitive gel showed the most advantageous properties in terms of injectability, pH gelation, and prolonged release of MB.

Formulation and performance evaluation of emulgel platform for combined skin delivery of curcumin and propolis

ABSTRACT The environmental can modify the physiology and body protective function of skin. Propolis (PRP) and curcumin (CUR) possess important antioxidant and antimicrobial properties, and they can be administered in the combined way and using photodynamic therapy (PDT). Emulgels can control the drug release due to the physicochemical properties of the gel and the emulsion. They constitute a good strategy for achieving an improved platform for combined delivery of PRP and CUR. There are no other studies of emulgels composed of PRP and CUR and their performance as antimicrobial and skin healing using or not PDT. This study aimed to investigate the effect of Carbopol 934P (C934P), 974P (C974P) or polycarbophil (PC) on physicochemical stability, antioxidant activity, drug release profile, antimicrobial activity, and ex vivo skin permeation and retention of emulgels containing PRP and CUR. Formulations containing C974P or PC displayed improved stability and antioxidant activity. They displayed activity against Staphylococcus aureus and modified (extended) drug release, governed mainly by non-Fickian anomalous transport. C974P and PC resulted in improved emulgels for combined CUR and PRP delivery, allow the drugs to cross the stratum corneum, and permeate the epidermis, reaching the dermis. The selected emulgels are candidates to further studies to prove their action and benefits to skin health.

Formulation and In Vitro Evaluation of Mucoadhesive Sustained Release Gels of Phytoestrogen Diarylheptanoids from Curcuma comosa for Vaginal Delivery

Diarylheptanoids (DAs) characterized by a 1,7-diphenylheptane structural skeleton are considered a novel class of phytoestrogens. The DAs available in Curcuma comosa Roxb. (C. comosa) extract demonstrated significant estrogenic activities both in vitro and in vivo. This study aimed to develop and comprehensively evaluate a mucoadhesive vaginal gel for the sustained release of DAs. Different mucoadhesive polymers as gelling agents were investigated. C. comosa ethanolic crude extract was used as a source of DAs. All C. comosa gels were light brown homogeneous with pH within 4.4-4.6. Their flow behaviors were pseudoplastic with a flow behavior index of 0.18-0.38. The viscosity at a low shear rate varied from 6.2 to 335.4 Pa·s. Their mechanical and extrudability properties were associated well with rheological properties. Polycarbophil (PCP):hydroxypropyl methylcellulose (HPMC) blends had a higher mucoadhesiveness to porcine vaginal mucosa than those of PCP-based or HPMC-based gels. All C. comosa gels exhibited a sustained, zero-order DA release pattern over 72 h. Korsmeyer and Peppas equation fitting indicated a non-Fickian, case II transport release mechanism. C. comosa gels had good physical and chemical stability under low-temperature storage for up to 12 months. PCP:HPMC-based mucoadhesive gels could be a proper delivery system for vaginal administration of DAs.

The influence of different bioadhesive polymers on physicochemical properties of thermoresponsive emulgels containing Amazonian andiroba oil

Emulgels are amphiphilic semi-solid that can control the delivery of drugs showing different polarities. The use of a polymeric matrix in the hydrophilic portion leads to a higher thermodynamic stability system. Emulgels composed of poloxamer 407 (P407) and a bioadhesive polymer has shown improved contact time and adhesiveness on the site of administration, which can lead to an increase in the bioavailability of drugs. This work studied the effect of three different bioadhesive polymers, namely Carbopol 974P (C974P), polycarbophil (PCB) and poly(vinyl methyl ether-alt-maleic anhydride) (PMV/MA), on physicochemical characteristics of emulsion systems containing P407 and Amazonian andiroba oil. This oil is utilized as emollient, humectant and antioxidant. A factorial design 34 was utilized, and the physicochemical stability was investigated. The mechanical textural and rheological properties of the most stable formulations were evaluated for selection of potential emulsion systems. According to the texture profile and softness analyses, the selected formulations were mainly influenced by the type and amount of bioadhesive polymer, increase of andiroba oil, and P407 content. All formulations displayed pseudoplastic flow behavior and viscoelasticity. Bioadhesion assays in ear porcine skin showed the formulations as being equally bioadhesive. Transmission electron cryomicroscopy (Cryo-TEM) analysis showed well-structured micelles, with a size < 200 nm. The use of C974P (0.20 %, w/w) and P407 (17.5 %, w/w) constitutes a good strategy to produce emulgel systems for local administration of Andiroba oil from 4 to 8 % (w/w).

Thermosensitive Polymer Blend Composed of Poloxamer 407, Poloxamer 188 and Polycarbophil for the Use as Mucoadhesive In Situ Gel.

Herein, thermosensitive blends of poloxamer 407 (P407)/poloxamer 188 (P188)/polycarbophil (PCB) were developed in terms of maximized content of PCB (a mucoadhesive polymer) and desired temperature-dependent rheological properties of the blends as in situ gelling matrices. Maximizing PCB content while achieving the preferable rheological characteristics was accomplished through the Box–Behnken design. The quantitative effect of the polymer composition in the blends on the thermosensitive characteristics was evaluated using the fitted design model and the corresponding surface plots. The optimized P407/P188/PCB blend (OPT) was the mixture of 20.000, 7.349 and 0.595% (w/w) of P407, P188, and PCB, respectively. The thermosensitive micellization of OPT was investigated using differential scanning calorimetry which revealed an overlapping double endothermic peak caused by the temperature-induced micellization of pure micelles in co-existence with the micelles with attached PCB. Mixing PCB with the P407/P188 matrix promoted a more intense mucoadhesion of the blend. After incorporating metronidazole, a model hydrophilic drug, into OPT, the temperature-dependent characteristics of the hydrogel did not change. Metronidazole release from OPT was sustained by an anomalous mechanism. This optimal ternary hydrogel benefiting from thermosensitive gelling and mucoadhesive matrix might be used as a viable platform for mucoadhesive in situ gelling drug delivery.

Medical Management of Constipation in Elderly Patients: Systematic Review.

Background/AimsConstipation is a common gastrointestinal problem in the elderly. Because of the limitations of life style modifications and the comorbidity, laxative use is also very common. Therefore, this study reviews the latest literature on the effect and safety of laxative in the elderly.MethodsA systematic review of randomized controlled trials investigating the effectiveness and safety of laxatives for constipation in elderly patients over 65 years old were performed using the following databases PubMed, EMBASE, and the Cochrane Library.ResultsTwenty-three randomized controlled trials were included in this review. Among the selected studies, 9 studies compared laxative with placebo and 5 studies compared laxatives of the same type. Four studies compared different types of laxatives or compared combination agents. Five studies compared novel medications such as prucalopride, lubiprostone, and elobixibat with placebo. Psyllium, calcium polycarbophil, lactulose syrup, lactitol, polyethylene glycol, magnesium hydroxide, stimulant laxative with or without fiber, and other medications were more effective than placebo in elderly constipation patients in short-term. Generally, the frequency and severity of adverse effects of laxative were similar between the arms of studies.ConclusionsBulk laxative, osmotic laxative, stimulant laxative with or without fiber, and other medications can be used in elderly patients in short-term within 3 months with reasonable safety. However, the quality of included studies was not high and most of studies was conducted in a small number of patients. Among these laxatives, polyethylene glycol seems to be safe and effective in long-term use of about 6 months in elderly patients.

Towards a better understanding of thermally treated polycarbophil matrix tablets for controlled release

Polycarbophil (POL), a polyacrylic acid cross-linked with divinyl glycol, is widely used in semisolid and solid dosage forms. When undergoing a thermal treatment in the range 120–160 °C, POL shows interesting morphological modifications, related to changes in physical properties, such as swelling of the powder granules, or hardening and matrix formation if included in the composition of a tablet. Thermal analysis conducted on POL highlighted a thermal event (Z) that can be correlated both to the shrinking of the powder granules and to the matrix formation in compacted POL powder. Modulated differential scanning calorimetry (MDSC) allowed to distinguish, inside event Z, an irreversible process overlapping with a reversible glass transition, attributable to the volatilization of residual solvents identified, through a complex TGA-FTIR-GC–MS interface, as acetate esters used for the polymer production as very fine powder. A specific interaction between acetates and POL, capable of stabilizing the polymer chains in a given conformation, was highlighted. The molecular rearrangement of the POL chains, following the volatilization of the solvent-stabilizers, is therefore ascribable to a loss of energetic stability of this material, which justifies the shrinking phenomena in the granules of the powder and the matrix formation when POL is compacted.

Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.

Design of enzyme decorated mucopermeating nanocarriers for eradication of H. pylori infection

The study was aimed to develop amoxicillin (AM) loaded thiomer based mucopermeating and mucoadhesive nanocarrier system that allows it to reach the bacterium, hiding in deeper mucus layers and extends its availability at infection site. Amoxicillin loaded nanocargoes were prepared using unmodified polycarbophil (PCP), thiolated polycarbophil (PCP-Cys), and papain modified thiolated polycarbophil (PCP-Cys-PAP) by ionic gelation method and processed for in vitro and ex vivo and in vivo characterization. All the nanocargoes were in size range of 111–288 nm. Drug loaded papain modified thiolated polycarbophil (AM-PCP-Cys-PAP) based nanocargoes showed an entrapment efficiency of 78 ± 7.2%, a zeta potential of − 13.4 mV and spherical shape. Both AM-PCP-Cys and AM-PCP-Cys-PAP exhibited a sustained release of drug up to 48 h and AM-PCP-Cys-PAP nanocargoes showed significant stability in acidic pH as compared to pure drug. Rheological investigation demonstrated a twofold higher mucoadhesion for thiolated polycarbophil nanocargoes. Ex vivo muco-penetration studies demonstrated deepest permeation of papain modified nanocargoes into the mucus. Cytotoxicity analysis showed that nanocarrier formulations were non-toxic to Caco-2 cells and maintained cell viability after 48 h. In vitro growth inhibition assay for H. pylori exhibited better efficacy for AM-PCP-Cys-PAP nanocargoes in terms of improved stability along with complete eradication of bacteria over prolonged period of time. In vivo acute toxicity studies on vital organs of mice exhibited no significant change in cell morphology. In vivo clearance study showed that AM-PCP-Cys-PAP nanoformulation was successful in complete eradication of bacteria. Based on above findings, amoxicillin loaded papain modified thiolated polycarbophil nanocarrier system was able to completely eradicate H. pylori infection that was attributed to its enhanced mucopermeating and mucoadhesive nature. The functionalized nanocarriers showed an interesting future potential for infectious therapy.

Mucoadhesive hydrogels for buccal drug delivery: In vitro-in vivo correlation study

AimIt was the aim of this study to assess in vitro methods for the characterization of mucoadhesive hydrogels for their potential to predict the residence time on human buccal mucosa. MethodsMixtures of hydrogels comprising hydroxyethyl cellulose (HEC), sodium carboxymethyl cellulose (CMC), xanthan gum (XTGM), hyaluronic acid sodium salt (HA), sodium alginate (ALG), carbopol (CP) as well as polycarbophil (PCP) and porcine mucus were analysed for relative rheological synergism. Furthermore, hydrogels were characterized for their texture and mechanical properties. For the assessment of mucoadhesive strength of formulations tensile studies were performed on porcine buccal mucosa. To facilitate a direct comparability of data the residence time of stained hydrogels was determined ex vivo on porcine buccal mucosa and in the oral cavity of volunteers. ResultsThe extent of relative rheological synergism was in good agreement with data from in vivo residence time studies. Results of tensile studies were further effected by textural properties of hydrogels leading to a restricted correlation with data from the in vivo experiment. The resistance towards removal by artificial saliva flow ex vivo revealed the highest correlation to the in vivo experiment with increasing mucosal residence time in the rank order CP < HEC, HA, ALG, PCP < CMC < XTGM. ConclusionsThis overview of measurement principles to predict the residence time of hydrogels for buccal application in humans may be a potent tool for the development of semisolid intraoral formulations.

Adhesive thermosensitive gels for local delivery of viral vectors.

Local delivery of viral vectors can enhance the efficacy of therapies by selectively affecting necessary tissues and reducing the required vector dose. Pluronic F127 is a thermosensitive polymer that undergoes a solution-gelation (sol-gel) transition as temperature increases and can deliver vectors without damaging them. While pluronics can be spread over large areas, such as the surface of an organ, before gelation, they lack sufficient adhesivity to remain attached to some tissues, such as the surface of the heart or mucosal surfaces. Here, we utilized blends of pluronic F127 and polycarbophil (PCB), a mucoadhesive agent, to provide the necessary adhesivity for local delivery of viral vectors to the cardiac muscle. The effects of PCB concentration on adhesive properties, sol-gel temperature transition and cytocompatibility were evaluated. Rheological studies showed that PCB decreased the sol-gel transition temperature at concentrations >1% and increased the adhesive properties of the gel. Furthermore, these gels were able to deliver viral vectors and transduce cells in vitro and in vivo in a neonatal mouse apical resection model. These gels could be a useful platform for delivering viral vectors over the surface of organs where increased adhesivity is required.

Mucoadhesive sustained-release tablets for vaginal delivery of Curcuma comosa extracts: Preparation and characterization

The objectives of this study were to prepare and characterize the mucoadhesive vaginal tablets of Curcuma comosa (C. comosa) extract for local delivery of the active phytoestrogens in a sustained release manner. The oleoresin-like C. comosa extract was converted into apparently dry powder by adding it into the mixture of polymer, namely polycarbophil (PCP), hydroxypropylmethylcellulose (HPMC) or the blends of PCP:HPMC, and silica. The absence of interaction between C. comosa extract and excipients was confirmed using FTIR. C. comosa mucoadhesive powder was directly compressed into 24-mm capsule shape tablets. All prepared tablets had acceptable physical properties and uniformity of diarylheptanoids (DAs), namely (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DA1) and (3S)-1,7-diphenyl-(6E)-4,6-hepten-3-ol (DA2). Blending PCP with HPMC could improve swelling and mucoadhesive properties of the tablets (p < 0.05). In vitro release showed that DAs were released over a period of 72 h in a sustained manner. The almost complete DA release was found in the formulation prepared with HPMC, of which the mean dissolution time of DA1 and DA2 stood at 34.7 ± 4.1 and 32.1 ± 3.7 h, respectively. Stability study reveals that C. comosa tablets were stable in terms of tablet properties, DA content and release characteristics when stored in a refrigerator.

Assessment of improved buccal permeation and bioavailability of felodipine microemulsion-based cross-linked polycarbophil gel.

The oral bioavailability of felodipine (FEL) is very low, i.e., about 15%. This could be due to low water solubility and hepatic first-pass effect. The objective of the present study was to develop FEL microemulsion-based gel, to bypass the first pass effect, for buccal delivery. The optimized FEL microemulsion (OPT-MEF) was used to prepare buccoadhesive gels, with varying concentrations of hydroxypropyl methylcellulose (HPMC) E4M and polycarbophil (PCP), and evaluated. The cross-linking of the PCP gelling agent was done by adjusting the pH with a neutralizing agent, triethanolamine (TEA). The formulations, namely drug suspension, OPT-MEF, microemulsion-based buccal gel containing 1% w/v (MEF-E4M1), 2% w/v (MEF-E4M2), and 3% w/v (MEF-E4M3) of HPMC K4M and 1% w/v (MEF-PCP1), 2% w/v (MEF-PCP2), and 3% w/v (MEF-PCP3) of PCP were prepared and optimized on the basis of ex vivo permeation study, mucoadhesion force, and viscosity. The optimized buccal gel (MEF-PCP1) showed significantly higher (p < 0.01) permeation flux (J = 0.44 ± 0.16mg/cm2/h), when compared with the drug suspension (J = 0.17 ± 0.14mg/cm2/h). The permeation enhancement ratio of MEF-PCP1 was found to be 2.59 times higher than that of the aqueous suspension of the drug. The texture profile analysis of MEF-PCP1 was performed which showed spreadability (3.2mJ), extrudability (151.8mJ), hardness (13.8g), and adhesiveness (41.0g), and results indicated good spreadability and adhesiveness. The rheological study revealed the pseudoplastic flow behavior of MEF-PCP1 buccal gel. The Cmax value 9.21 ± 2.88μg/ml of MEF-PCP1 gel was found to be significantly higher (P < 0.01) compared to the same dose administered by oral route (Cmax value 3.51 ± 1.74μg/ml). The relative bioavailability (Fr) of the optimized MEF-PCP1 buccal gel was about 397.39% higher than that of oral route. In conclusion, consistent and effective buccal gel containing optimized FEL-loaded microemulsion, with improved buccal permeation and pharmacokinetic parameters was developed successfully to improve the bioavailability of FEL.

Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles

The aims of this study were to prepare and characterize hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend films saturated with propranolol hydrochloride (PNL)-loaded nanoparticles to improve permeability of drugs that undergo first-pass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL (70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles (PN-films) and HPMC/PC blend films containing PNL (80 mg/film) without nanoparticles (PP-films) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope (SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film (PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index (SI) of all PN-films and PP-films increased greatly in the first period time (10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points (10–30 min). After 120 min, the release of PN-films-70 was lower than the other PN-films. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.

Screening of anionic-modified polymers in terms of stability, disintegration, and swelling behavior

This study aimed to screen the stability, disintegration, and swelling behavior of chemically modified anionic polymers. Investigated polymers were well-known and widely used staples of the pharmaceutical and medical field, namely, alginate (AL), carboxymethyl cellulose (CMC), polycarbophil (PC), and hyaluronic acid (HA). On the basis of amide bond formation between the carboxylic acid moieties of anionic polymers and the primary amino group of the modification ligand cysteine (CYS), the modified polymers were obtained. Unmodified polymers served as controls throughout all studies. With the Ellman’s assay, modification degrees were determined of synthesized polymeric excipients. Stability assay in terms of erosion study at physiological conditions were performed. Moreover, water uptake of compressed polymeric discs were evaluated and further disintegration studies according to the USP were carried out to define the potential ranking. Results ranking figured out PCCYS > CMCCYS > HACYS > ALCYS in terms of water uptake capacity compared to respective controls. Cell viability assays on Caco-2 cell line as well as on RPMI 2650 (ATTC CCL30) proved modification not being harmful to those. Due to the results of this study, an intense screening of prominent anionic polymer derivate was performed in order to help the pharmaceutical research for the best choice of polymeric excipients for developments of controlled drug release systems.

Comprehensive mucoadhesive study of anionic polymers and their derivate

AimThe purpose was to compare the mucoadhesive properties of well-known anionic polymers such as alginate (AL), carboxymethyl cellulose (CMC), polycarbophil (PC) and hyaluronic acid (HA) with regards to potential improvement in mucoadhesiveness based on chemical modification. MethodsAL, CMC, PC and HA, respectively, were modified with sulfhydryl groups of cysteine (CYS) on their polymeric backbone via amide bond formation. Viability and safety was evaluated on mucosal surface. Histology imaging was taken via H&E staining. Intense mucoadhesive studies were performed on mucosal tissue determining residence time, adhesion and total work of adhesion as well as maximum detachment force of unmodified and modified polymers, respectively. ResultsBoth polymers, unmodified anionic and modified ones, exhibit no toxicity at all. Histology imaging was in good agreement with the viability study on the mucosal surface. Unmodified anionic polymers reveal limited mucoadhesiveness whereas modified polymers showed up to 2.18-fold, 2.77-fold, 16.29-fold and 59.23-fold more pronounced total work of adhesion in case of CMCCYS, HACYS, PCCYS and ALCYS, respectively. ConclusionThis comprehensive study provides deep understanding for the appropriate choice of mucoadhesive excipient for the development of mucosal drug delivery systems.

Preparation and Characterization of Hydroxypropyl Methylcellulose/Polycarbophil Mucoadhesive Blend Films Using a Mixture Design Approach.

The objectives of this study were to prepare the hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend film and to investigate the main and interaction effect of HPMC and PC mixtures on the physicochemical and mechanical properties of blend films using a simplex lattice mixture design approach. The cubic and quadratic models were selected to analyze mucoadhesive properties in terms of work of adhesion and maximum detachment force, respectively. It was shown that HPMC/PC blend film had higher mucoadhesive properties than pure HPMC film. The suitable models for analyzing swelling index of blend films at various times were assessed. The puncture strength, % elongation and hydrophilicity of films were also examined. The pure HPMC film displayed more homogeneous and smoother structures compared with the blend film, as observed by scanning electron microscope and atomic force microscopy. Intermolecular hydrogen bonding between HPMC and PC was detected using Fourier transform infrared and X-ray diffraction. Therefore, the blend film shows high potential for use as a buccal delivery system.

Strontium-containing, carbohydrate-based polymer networks as tooth-adherent systems for the treatment of dentine hypersensitivity

This study describes the design/physicochemical properties of strontium-containing, mucoadhesive carbohydrate polymeric platforms, designed as treatments for dentine hypersensitivity. Interactive networks were composed of strontium chloride (10% w/w), one of two base polymers (sodium carboxymethylcellulose, NaCMC or hydroxyethylcellulose, HEC), polycarbophil (PC) and, when required, polyvinylpyrrolidone (PVP). The physicochemical properties were characterised using oscillatory and flow rheometry, texture profile analysis, mucoadhesion analysis and, additionally, the strontium release properties were examined. All platforms exhibited pseudoplastic flow. Increasing polymer concentrations increased network viscoelasticity, consistency, hardness, compressibility, gel strength, adhesiveness, mucoadhesion and, retarded strontium release. Principally zero-order strontium release was observed from all platforms. Incorporation of strontium reduced the network elasticity, consistency, hardness, compressibility, gel strength and mucoadhesion; HEC-based platforms being affected to a greater extent than NaCMC platforms. NaCMC-based platforms containing 10% strontium chloride, PVP (3% w/w) and PC (3% w/w) potentially displayed the correct balance of physicochemical properties for the treatment of dentine sensitivity.

Functional Outcomes of Patients Treated with Intensive Medications for Bowel and Pain Control for Low-Lying Rectal Cancer Who Received Preoperative Chemoradiotherapy

Purpose: The aim of this study was to assess the functional outcomes of patients treated with intensive medications for bowel and pain control for low-lying rectal cancer who received preoperative chemoradiotherapy (CRT). Methods: The inclusion criterion was sphincter-preserving surgery following CRT for T3 middle and low rectal cancer. Postoperative defecation control was conducted using calcium polycarbophil and loperamide, and anal pain control was conducted using oxycodone hydrochloride hydrate. The functional outcomes were determined by an annual questionnaire after stoma closure. Results: Of 64 patients evaluated, 33 were reconstructed using the double stapling technique (DST) and 31 were reconstructed using the intersphincteric resection (ISR) technique. The median Visual Analogue Scale at ISR was improved from 7 to 1.5 at 1 year after surgery. The median Wexner scores were 6.0, 6.0, 5.0 and 5.0 for DST and 14.5, 12.0, 10.0 and 8.0 for ISR for the first 4 years, respectively. The only independent predictor of a poor bowel function (Wexner score >10) according to a multivariate analyses was pelvic infection (OR 3.994, 95% CI 1.235-13.52, p = 0.021), while ISR was not a predictor. Conclusions: Anal pain following ISR can be controlled with oxycodone hydrochloride hydrate therapy. ISR is feasible following CRT for low-lying rectal cancer.

American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation.

Irritable bowel syndrome (IBS) and chronic idiopathic constipation ((CIC) also referred to as functional constipation) are two of the most common functional gastrointestinal disorders worldwide. IBS is a global problem, with anywhere from 5 to 15 % of the general population experiencing symptoms that would satisfy a defi nition of IBS ( 1,2 ). In a systematic review on the global prevalence of IBS, Lovell and Ford ( 1 ) documented a pooled prevalence of 11 % with all regions of the world suff ering from this disorder at similar rates. Given its prevalence, the frequency of symptoms, and their associated debility for many patients and the fact that IBS typically occurs in younger adulthood, an important period for furthering education, embarking on careers, and / or raising families, the socioeconomic impact of IBS is considerable. Th ese indirect medical costs are frequently compounded by the direct medical costs related to additional medical tests and the use of various medical and nonmedical remedies that may have limited impact. CIC is equally common; in another systematic review, Suares and Ford ( 3 ) reported a pooled prevalence of 14 % , and also noted that constipation was more common in females, in older subjects, and those of lower socioeconomic status ( 3 ). Chronic constipation has also been linked to impaired quality of life ( 4 ), most notably among the elderly ( 5 ). Neither IBS nor CIC are associated with abnormal radiologic or endoscopic abnormalities, nor are they associated with a reliable biomarker; diagnosis currently rests entirely, therefore, on clinical grounds. Although a number of clinical defi nitions of both IBS and CIC have been proposed, the criteria developed through the Rome process, currently in its third iteration, have been those most widely employed in clinical trials and, therefore, most relevant to any review of the literature on the management of these disorders. According to Rome III, IBS is defi ned on the basis of the presence of: