Zein and hydroxypropyl methylcellulose acetate succinate microfibers combined with metronidazole benzoate and/or metronidazole-incorporated cellulose nanofibrils for potential periodontal treatment.

The development of flexible and porous materials to control antibacterial delivery is a pivotal endeavor in medical science. In this study, we aimed to produce long and defect-free fibers made of zein and hydroxypropyl methylcellulose acetate succinate (HPMCAS) to be used as a platform for the release of metronidazole (MDZ) and metronidazole benzoate (BMDZ) to be potentially used in periodontal treatment. Microfibers prepared via electrospinning under a 2:3 (w/w) zein to HPMCAS ratio, containing 0.5 % (w/w) poly(ethylene oxide) (PEO) and 1 % (w/w) cellulose nanofibril (CNF) were loaded with 40 % (w/w) MDZ, 40 % (w/w) BMDZ, or a combination of 20 % (w/w) of each drug. The addition of CNF improved the electrospinning process, resulting in long fibers with reduced MDZ and BMDZ surface crystallization. MDZ- and BMDZ-incorporated fibers were semicrystalline and displayed commendable compatibility among drugs, nanocellulose and polymeric chains. Release tests showed that zein/HPMCAS/PEO fibers without CNF and with 20 % (w/w) MDZ/ 20 % (w/w) BMDZ released the drug at a slower and more sustained rate compared to other samples over extended periods (up to 5 days), which is a favorable aspect concerning periodontitis treatment.

Solid dispersions based on chitosan/hypromellose phthalate blends to modulate pharmaceutical properties of zidovudine.

Zidovudine (AZT) has been widely used alone or in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus. Its erratic oral bioavailability necessitates frequent administration of high doses, resulting in severe side effects. In this study, the design of mucoadhesive solid dispersions (SDs) based on chitosan (CS) and hypromellose phthalate (HP) was rationalized as a potential approach to modulate AZT physicochemical and pharmaceutical properties. SDs were prepared at different drug:polymer ratios, using an eco-friendly technique, which avoids the use of organic solvents. Particles with diameter from 56 to 73 µm and negative zeta potentials (-27 to -32 mV) were successfully prepared, achieving high drug content. Infrared spectroscopy revealed interactions between polymers but no interactions between the polymers and AZT. Calorimetry and X-ray diffraction analyses showed that AZT was amorphized into the SDs. The mucoadhesive properties of SDs were evidenced, and the control of AZT release rates from the matrix was achieved, mainly in acid media. The simple, low-cost, and scalable technology proposed for production of SDs as a carrier platform for AZT is an innovative approach, and it proved to be a feasible strategy for modulation the physico-chemical, mucoadhesive, and release properties of the drug.

Alginate-based microparticles coated with HPMCP/AS cellulose-derivatives enable the Ctx(Ile21)-Ha antimicrobial peptide application as a feed additive.

Microencapsulation is a potential biotechnological tool, which can overcome antimicrobial peptides (AMP) instabilities and reduce toxic side effects. Thus, this study evaluates the antibacterial activities of the Ctx(Ile21)-Ha AMP against multidrug-resistant (MDR) and non-resistant bacteria and develop and characterize peptide-loaded microparticles coated with the enteric polymers hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose phthalate (HPMCP). Ctx(Ile21)-Ha was obtained by solid phase peptide synthesis (SPPS) method, purified and characterized by HPLC and Mass Spectrometry. The peptide exhibited potent antibiotic activities against Salmonella enteritidis, Salmonella typhimurium, Pseudomonas aeruginosa (MDR), Acinetobacter baumannii (MDR), and Staphylococcus aureus (MDR). Ctx(Ile21)-Ha microencapsulation was performed by ionic gelation with high efficiency, maintaining the physical-chemical stability. Ctx(Ile21)-Ha coated-microparticles were characterized by DSC, TGA, FTIR-Raman, XRD and SEM. Hemolytic activity assay demonstrated that hemolysis was decreased up to 95% compared to single molecule. In addition, in vitro release control profile simulating different portions of gastrointestinal tract was performed and showed the microcapsules' ability to protect the peptide and release it in the intestine, aiming pathogen's location, mainly by Salmonella sp. Therefore, use of microencapsulated Ctx(Ile21)-Ha can be allowed as an antimicrobial controller in monogastric animal production as an oral feed additive (antimicrobial controller), being a valuable option for molecules with low therapeutic indexes or high hemolytic rates.

New supersaturating drug delivery system as strategy to improve apparent solubility of candesartan cilexetil in biorelevant medium.

Candesartan cilexetil (CC) is a poorly soluble antihypertensive drug with in vivo absorption limited by its low aqueous solubility. Aiming to generate CC supersaturation as strategy to improve its absorption and bioavailability, amorphous solid dispersions (ASDs) of CC with hydroxypropylmethylcellulose acetate succinate type M (HPMCAS M) were developed and evaluated by in vitro and in vivo techniques. The ASDs were characterized by several solid-state techniques and evaluated regarding the supersaturation generation and maintenance under non-sink conditions in biorelevant medium. Stability studies at different storage conditions and in vivo pharmacodynamics studies were performed for the best formulation. The ASD developed presented appropriate drug amorphization, confirmed by solid state characterization, and CC apparent solubility increases around 85 times when compared to the pure crystalline drug. Supersaturation was maintained for up to 24 h in biorelevant medium. The in vivo pharmacodynamics studies revealed that ASD of CC with the polymer HPMCAS M presented an onset of action about four times faster when compared to the pure crystalline drug. The CC-HPMCAS ASD were successfully developed and demonstrated good physical stability under different storage conditions as well as promising results that indicated the ASD potential for improvement of CC biopharmaceutical properties.

Preparation of a solid self-microemulsifying drug delivery system by hot-melt extrusion.

Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined. The extrudates were then obtained by blending the lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical microscopy and PXRD were used to characterize the extrudates. In vitro microemulsion reconstitution and drug release were also studied. L-SMEDDS gave rise to microemulsions with low mean size, PdI and zeta potential (140.04 ±â€¯7.22 nm, 0.219 ±â€¯0.011 and -9.77 ±â€¯0.86 mV). S-SMEDDS were successfully prepared by HME, and an HMPCAS matrix was able to avoid microemulsion reconstitution and retain drug release in pH 1.2 (12.97%-25.54%). Conversely, microemulsion reconstitution and drug release were gradual in pH 6.8 and complete for some formulations. Extrudates prepared at the lowest drug concentration and highest temperature and recirculation time promoted a complete and rapid drug release in pH 6.8 giving rise to small and uniform microemulsion droplets.

HPMCAS as an effective precipitation inhibitor in amorphous solid dispersions of the poorly soluble drug candesartan cilexetil.

Among the strategies to improve the biopharmaceutic properties of poorly soluble drugs, Supersaturating Drug Delivery Systems like polymer-based amorphous solid dispersions (SD) have been successfully applied. The screening of appropriate polymeric carriers to compose SD is a crucial point on their development. In this study, hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose acetate succinate (HPMCAS) types L, M and H and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL) were evaluated by in vitro supersaturation studies regarding their anti-precipitant ability on the poorly soluble drug candesartan cilexetil (CC) under two different media, including biorelevant conditions. According to the results, HPMCAS M was considered the best carrier to develop SD containing CC among all the polymers tested, due to its good anti-precipitant performance in both media. In addition, the medium used in the in vitro supersaturation studies played an important role on the results, and its selection should be carefully done.

Development and characterization of lipid-polymeric nanoparticles for oral insulin delivery.

INTRODUCTION: The oral route is widely accepted as the most physiological path for exogenous administration of insulin, as it closely mimic the endogenous insulin pathway. Thus, in this work it is proposed an innovative lipid-polymeric nanocarrier to delivery insulin orally. Areas covered: Nanoparticles were produced through a modified solvent emulsification-evaporation method, using ethyl palmitate and hydroxypropylmethylcellulose acetate succinate as matrix. Lipid-polymeric nanoparticles were around 300 nm in size, negatively charged (-20 mV) and associated insulin with efficiency higher than 80%. Differential scanning calorimetry suggested thermal stability of nanoparticles. In vitro release assays under simulated gastrointestinal conditions resulted in 9% and 14% of insulin released at pH 1.2 during 2 h and at pH 6.8 for 6 h, respectively, demonstrating the ability of those nanoparticles to protect insulin against premature degradation. Importantly, nanoparticles were observed to be safe at potential therapeutic concentrations as did not originate cytotoxicity to intestinal epithelial cells. Lastly, the permeability of nanoencapsulated insulin through Caco-2 monolayers and a triple Caco-2/HT29-MTX/Raji B cell model correlated well with slow release kinetics, and fosters the effectiveness of nanoparticles to promote intestinal absorption of peptidic drugs. Expert opinion: Lipid-polymeric nanoparticles were developed to encapsulate and carry insulin through intestine. Overall, nanoparticles provide insulin stability and intestinal permeability.

Salivary stimulation by prolonged release of pilocarpine in sjõgren’ syndrome

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

Biopolymeric antimicrobial films: study of the influence of hydroxypropyl methylcellulose, tapioca starch and glycerol contents on physical properties.

Mixture design methodology was applied to study the effect of different levels of tapioca starch (TS), hydroxypropyl methylcelullose (HPMC), and glycerol (Gly) on the physical properties of biopolymeric films supporting potassium sorbate (KS; 0.3% w/w) with the goal of contributing to the development of materials for preventing food surface contamination. Mechanical properties, water vapour permeability (WVP), solubility in water (S) and colour attributes were evaluated on the films. HPMC addition produced an increase of elastic modulus (Ec), stress at break (σb) and S. It also decreased the yellow index (YI) values and the strain at break (εb). The study was deepened using the formulation containing 2.67 g/100g of TS, 0.67 g/100g of HPMC, 1.67 g/100g Gly and 0.3g/100g KS, observing that it behaved as an effective antimicrobial barrier against Zygosaccharomyces bailii external contamination. Microstructural analysis allowed us to conclude that HPMC incorporation to a TS network decreased roughness of the films and it also increased permeability to oxygen (PO2).

Spray-dried O-carboxymethyl chitosan as potential hydrophilic matrix tablet for sustained release of drug.

OBJECTIVE: The aim of the present investigation was to evaluate the use of spray-dried O-carboxymethyl chitosan (OCMCS) as potential hydrophilic matrix excipient for sustained release of drug. METHODS: The polymer was synthesized from chitosan, then spray-dried and characterized. Tablets with different OCMCS concentrations (80, 50, 30, 5 and 2% w/w), containing diltiazem (DTZ) as model drug, were prepared for direct compression (DC) and after the wet granulation method (WG). RESULTS: The spray-dried OCMCS powder was spherical, with a smooth surface and an average size of 2.2 µm. The tablets prepared for WG disintegrated in time less than 30 min. The tablets obtained for DC presented high retention of the drug, with zero order or Higuchi release kinetic. There was a direct relationship between the OCMCS concentration and the release ratio, swelling degree and water uptake behavior. DC tablets containing 80% OCMCS presented behavior as an effective swelling-control system. The DC tablets with 5% OCMCS showed a similar release profile at formulations with 30% HPMC. CONCLUSION: Spray-dried OCMCS showed great potential as hydrophilic matrices for drug-sustained release.

Formulation development and stability studies of norfloxacin extended-release matrix tablets.

The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at 40 ± 2°C and 75 ± 5% relative humidity), and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo.

NIR imaging spectroscopy for quantification of constituents in polymers thin films loaded with paracetamol.

Thin films loaded with the drug paracetamol were produced from polymer blends formed by hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyethyleneglycol (PEG), at various mass ratios of polymers and drug defined by a D-optimal experimental design. NIR hyperspectral images were obtained from each thin film formulation and the pixel-to-pixel quantification of the constituents were carried out by partial least square (PLS) and multivariate curve resolution-alternating least square (MCR-ALS) with three different calibration/validation strategies. These strategies differ in the way to construct the calibration and validation matrices and they had to be carried out to suppress the bias on the quantification of the constituents in the polymer blend. The errors of prediction in the models from MCR-ALS were influenced by the calibration/validation strategy employed, but they were similar to the ones from PLS model. Concentration distribution maps were built after pixel-to-pixel predictions and their characteristics were analyzed.

A clinical comparison between DisCoVisc and 2% hydroxypropylmethylcellulose in phacoemulsification: a fellow eye study.

OBJECTIVE: This study sought to compare the effects and outcomes of two ophthalmic viscosurgical devices, 1.6% hyaluronic acid/4.0% chondroitin sulfate and 2.0% hydroxypropylmethylcellulose, during phacoemulsification. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that received phacoemulsification performed by the same surgeon using a standardized technique. Patients were randomly assigned to receive either 1.6% hyaluronic acid/4.0% chondroitin sulfate or 2.0% hydroxypropylmethylcellulose on the first eye. The other eye was treated later and received the other viscoelastic agent. Preoperative and postoperative examinations (5, 24 and 48 hours; 7 and 14 days; 3 and 6 months) included measurements of the total volume of the ophthalmic viscosurgical device, ultrasound and washout times to completely remove the ophthalmic viscosurgical device, intraocular pressure, central corneal thickness and best-corrected visual acuity. The corneal endothelial cell count was measured at baseline and at six months postoperatively. ClinicalTrials.gov: NCT01387620. RESULTS: There were no statistically significant differences between groups in terms of cataract density or ultrasound time. However, it took longer to remove 2.0% hydroxypropylmethylcellulose than 1.6% hyaluronic acid/ 4.0% chondroitin sulfate, and the amount of viscoelastic material used was greater in the 2.0% hydroxypropylmethylcellulose group. In addition, the best-corrected visual acuity was significantly better in the hyaluronic acid/ chondroitin sulfate group, but this preferable outcome was only observed at 24 hours after the operation. There were no statistically significant differences between the two ophthalmic viscosurgical devices regarding the central corneal thickness or intraocular pressure measurements at any point in time. The corneal endothelial cell count was significantly higher in the hyaluronic acid/chondroitin sulfate group. CONCLUSION: The ophthalmic viscosurgical device consisting of 1.6% hyaluronic acid/4.0% chondroitin sulfate was more efficient during phacoemulsification and was easier to remove after IOL implantation than 2.0% hydroxypropylmethylcellulose. In addition, the corneal endothelial cell count was significantly higher following the use of hyaluronic acid/chondroitin sulfate than with hydroxypropylmethylcellulose, which promoted an improved level of corneal endothelium protection.

A clinical comparison between DisCoVisc and 2% hydroxypropylmethylcellulose in phacoemulsification: a fellow eye study

OBJECTIVE: This study sought to compare the effects and outcomes of two ophthalmic viscosurgical devices, 1.6% hyaluronic acid/4.0% chondroitin sulfate and 2.0% hydroxypropylmethylcellulose, during phacoemulsification. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that received phacoemulsification performed by the same surgeon using a standardized technique. Patients were randomly assigned to receive either 1.6% hyaluronic acid/4.0% chondroitin sulfate or 2.0% hydroxypropylmethylcellulose on the first eye. The other eye was treated later and received the other viscoelastic agent. Preoperative and postoperative examinations (5, 24 and 48 hours; 7 and 14 days; 3 and 6 months) included measurements of the total volume of the ophthalmic viscosurgical device, ultrasound and washout times to completely remove the ophthalmic viscosurgical device, intraocular pressure, central corneal thickness and best-corrected visual acuity. The corneal endothelial cell count was measured at baseline and at six months postoperatively. ClinicalTrials.gov: NCT01387620. RESULTS: There were no statistically significant differences between groups in terms of cataract density or ultrasound time. However, it took longer to remove 2.0% hydroxypropylmethylcellulose than 1.6% hyaluronic acid/ 4.0% chondroitin sulfate, and the amount of viscoelastic material used was greater in the 2.0% hydroxypropylmethylcellulose group. In addition, the best-corrected visual acuity was significantly better in the hyaluronic acid/ chondroitin sulfate group, but this preferable outcome was only observed at 24 hours after the operation. There were no statistically significant differences between the two ophthalmic viscosurgical devices regarding the central corneal thickness or intraocular pressure measurements at any point in time. The corneal endothelial cell count was significantly higher in the hyaluronic acid/chondroitin sulfate group. CONCLUSION: The ophthalmic viscosurgical device consisting of 1.6% hyaluronic acid/4.0% chondroitin sulfate was more efficient during phacoemulsification and was easier to remove after IOL implantation than 2.0% hydroxypropylmethylcellulose. In addition, the corneal endothelial cell count was significantly higher following the use of hyaluronic acid/chondroitin sulfate than with hydroxypropylmethylcellulose, which promoted an improved level of corneal endothelium protection.

Physical properties of emulsion-based hydroxypropyl methylcellulose films: effect of their microstructure.

The initial characteristics of emulsions and the rearrangement of the oil droplets in the film matrix during film drying, which defines its microstructure, has an important role in the physical properties of the emulsion-based films. The objective of this work was to study the effect of the microstructure (two droplet size distributions) and stability (with or without surfactant) of HPMC oil-in-water emulsions over physical properties of HPMC emulsion-based edible films. HPMC was used to prepare sunflower oil-in-water emulsions containing 0.3 or 1.0% (w/w) of oil with or without SDS, as surfactant, using an ultrasonic homogenizer. Microstructure, rheological properties and stability of emulsions (creaming) were measured. In addition, microstructure, coalescence of oil droplets, surface free energy, optical and mechanical properties and water vapor transfer of HPMC films were evaluated. Image analysis did not show differences among droplet size distributions of emulsions prepared at different oil contents; however, by using SDS the droplet size distributions were shifted to lower values. Volume mean diameters were 3.79 and 3.77 µm for emulsions containing 0.3 and 1.0% without surfactant, respectively, and 2.72 and 2.71 µm for emulsions with SDS. Emulsions formulated with 1.0% of oil presented higher stability, with almost no change during 5 and 3 days of storage, for emulsions with and without SDS, respectively. Internal and surface microstructure of emulsion-based films was influenced by the degree of coalescence and creaming of the oil droplets. No effect of microstructure over the surface free energy of films was found. The incorporation of oil impaired the optical properties of films due to light scattering of light. Addition of oil and SDS decreased the stress at break of the emulsion-based films. The replace of HPMC by oil and SDS produce a lower "amount" of network structure in the films, leading to a weakening of their structure. The oil content and SDS addition had an effect over the microstructure and physical properties of HPMC-based emulsions which lead to different microstructures during film formation. The way that oil droplets were structured into the film had an enormous influence over the physical properties of HPMC films.

Using white sorghum flour for gluten-free breadmaking.

Cornstarch/sorghum flour (X1) ratio, water added (X2) and amount of hydroxypropyl methylcellulose (HPMC) used (X3) were varied for making gluten-free bread so as to optimize batter softness (Y1), specific volume (Y2) and crumb grain (Y3). A second-order model was employed to generate a response surface. It was found that the softness of the batter depends significantly on three factors in a linear way. The specific volume (Y2), in particular, was increased significantly with the increment of X1 and X3. The crumb grain (Y3) depended significantly on three factors, its scores increased with X1 and decreased with the water added (X2). Finally, 0.55 cornstarch/sorghum flour ratio, 90% of water added and 3% of HPMC were chosen as the best conditions, considering acceptable levels of specific volume and of crumb grain, and also taking into account the possibility of using the highest proportion of sorghum flour.

Complementary near-infrared and Raman chemical imaging of pharmaceutical thin films.

Complementary near-infrared (NIR) and Raman mapping techniques have been used to study the distribution of drug particles suspended in a polymeric film. The film configuration was used with the goal of maintaining a drug with a particle size of less than 10 µm in a nonagglomerated form and to satisfy two commonly encountered pharmaceutical needs: enhanced dissolution rate of poorly soluble drugs and the content uniformity of drugs administered in low doses. A total of four film batches were prepared for this study using hydroxypropyl methylcellulose (HPMC) with griseofulvin as the active pharmaceutical ingredient. The NIR method analyzed a film area of 3 × 2.6 mm, whereas Raman mapping analyzed an area of 10 × 10 µm, and every sample was analyzed by the two methods. The second derivative transform removed baseline variations in the NIR spectra and provided differentiation between the two components. NIR chemical imaging did not identify clusters larger than 0.05 mm. Raman analysis identified areas rich in griseofulvin or HPMC, which were used to develop a partial least squares discriminant analysis method to determine drug or polymer distribution throughout the film.

Benznidazole microcrystal preparation by solvent change precipitation and in vivo evaluation in the treatment of Chagas disease.

Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results.

Assembled modules technology for site-specific prolonged delivery of norfloxacin.

The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for individual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability.

Comparative results of gastric submucosal injection with hydroxypropyl methylcellulose, carboxymethylcellulose and normal saline solution in a porcine model.

CONTEXT: Endoscopic mucosal resection is an established modality for excision of sessile lesions in the gastrointestinal tract. Submucosal fluid injection creates a cushion and may prevent thermal injury and perforation. OBJECTIVES: This blind study investigated the performance of three different solutions to create submucosal fluid cushions in porcine stomach. METHODS: Three solutions were injected in the stomach of nine pigs BR1: normal saline solution, carboxymethylcellulose 0.5% and hydroxypropyl methylcellulose 0.25%. In each pig, submucosal injections with 6 mL per test-solution were performed. One drop of methylene blue was added to all injections for better visualization. The time for the bleb to disappear was recorded. RESULTS: The overall median time of visible submucosal cushion was 37 minutes (range 12-60 min) for hydroxypropyl methylcellulose, 31 minutes for carboxymethylcellulose (range 10-43 min) and 19 minutes for normal saline solution (range 8-37 min). There was no statistically significant difference neither between normal saline solution and carboxymethylcellulose (P = 0.146) nor carboxymethylcellulose and hydroxypropyl methylcellulose (P = 0.119) but the median duration of hydroxypropyl methylcellulose was significantly longer than normal saline solution (P = 0.039). CONCLUSIONS: The length of hydroxypropyl methylcellulose submucosal fluid cushion is longer in comparison with normal saline solution. The median time for carboxymethylcellulose was not longer than normal saline solution. Hydroxypropyl methylcellulose, in the concentration of 0.25%, may be a durable alternative for submucosal injection.