Semi-solid Nature Research Articles

Rheological properties of model emulsions containing oleosomes

AbstractIn the presented research, oleosomes were obtained from unroasted hazelnuts in an aqueous environment with a pH of 9.5, adjusted using sodium bicarbonate. Model emulsions were then prepared to contain oleosomes in proportions of 15, 25, and 35%. Rheological and viscosity analyses were conducted on these model emulsions, focusing on elastic and viscous modulus values. The results of the analyses, which revealed that an increase in the oleosome content in the model emulsions correlated with a concurrent increase in emulsion viscosity as well as in the elastic (G′) and viscous (G″) moduli, demonstrate the significant impact of oleosome concentration on the rheological properties of the emulsions. All samples exhibited a G′ > G″ relationship, indicating their semi-solid nature. Moreover, an increase in the oleosome content was found to result in a higher consistency index for the product, while the flow index remained largely unchanged.

Design and Optimization of 3D-Printed Tablets Containing Mucuna Extracts for Erectile Dysfunction Management: A DoE-Guided Study.

Erectile dysfunction (ED) refers to the inability of the penis to maintain a firm erection during sexual activity. Mucuna, or M. pruriens, contains levodopa, a compound showing promise in ED treatment. However, formulating Mucuna extract into tablet dosage forms is challenging due to its semisolid nature. This study aimed to develop sustained-release tablets containing Mucuna extract via semisolid extrusion 3D printing. Eudragit RS PO (Eudragit) served as a sustained-release polymer, with poly (vinyl alcohol) (PVA) as a co-polymer for forming the tablet matrices. This study had the following two main phases: screening, which identified the factors affecting the printability, and optimization, which focused on the factors influencing the levodopa release and its consistency. The results showed that both the polymeric solid percentage content (PSPC) in the semisolid slurry and the Eudragit-PVA ratio significantly affected the printability. All of the formulations were printable, and the PSPC and Eudragit-PVA ratios were incorporated into the optimized model. The desired formulation, achieving targeted levodopa release and consistency, had a PSPC of 58.8% and a Eudragit-PVA ratio of 2.87:1. In conclusion, semisolid extrusion 3D printing guided by the design of experiments (DoE) proved feasible for producing reliable 3D-printed tablets with consistent active ingredients and desired release rates.

Ionic Liquid‐Supported Single‐Sodium‐Ion‐Conducting Styrene‐Maleic Anhydride Copolymer for Energy Storage Devices

Wide‐ranging research has been done on ionic liquid (IL)‐incorporated conducting polymers in energy storage devices. Herein, by taking the reaction advantage of styrene maleic anhydride (SMA) copolymer with sodium hydroxide, a sodium ion having polymeric material as an electrolyte is synthesized. 1,8‐Diazabicyclo[5.4.0]undec‐7‐enium acetate (DBU acetate) is prepared as an IL and added to the prepared polymer electrolyte to increase the matrix flexibility, semisolid nature, and ionic mobility inside the matrix. This semisolid sodium ion‐based electrolyte shows conductivity in the order of 10−5 S cm−1 and an electrochemical stability window of 2.52 volts with >97% of ionic transference. It also shows the diffusivity constant in the order of 10−4 m2 s−1 and ionic mobility in the order of 10−3 m2 v−1 s−1 at 30 °C. The hydrogel matrix shows a correlated type of hopping with a power exponent <1 at 30 °C with low‐energy requirement of ionic transport, that is, 0.709 eV. A high amount of capacitance is associated with electrolyte that has an insignificant electrode contribution. On behalf of these findings, SMA‐IL‐based semisolid polymer electrolyte confirms its potential for application in sodium ion‐based energy storage systems.

Diagnostic Protocols for Evaluating the Degradation Mechanisms in Gel-Polymer Lithium Batteries.

Gel polymer electrolytes (GPEs) present a promising alternative to standard liquid electrolytes (LE) for Lithium-ion Batteries (LIBs) and Lithium Metal Batteries bridging the advantages of both liquid and solid polymer electrolytes. However, their cycle life still lags behind that of standard LIBs, and their degradation mechanisms remain poorly understood. A significant challenge is the need for specific diagnostic protocols to systematically study the degradation mechanisms of GPE-based cells. Challenges include the separation of cell components and effective washing, as well as the study of the solid electrolyte interfaces, all complicated by the semi-solid nature of GPEs. This paper provides a brief review of existing literature and proposes a comprehensive set of diagnostic tools for dismantling and evaluating the degradation of GPE-based LIBs. Finally, these methods and recommendations are applied to LiNi0.5Mn1.5O4 (LNMO)-graphite cells, revealing electrolyte oxidation as a major source of cell degradation.

Emulsion gel-based inks for 3D printing of foods for dysphagia patients: High internal type emulsion gel-biopolymer systems

High internal type emulsion gels (HIPE gels) are usually a soft semi-solid material consisting of tightly packed oil droplets stabilized by a layer of emulsifier. The semi-solid nature of HIPE gels means they can be used as edible inks in 3D food printing applications. However, the rheological properties of HIPE gels are typically unable to satisfy the demands of 3D printing applications, resulting in unsatisfactory printing performance. In this study, HIPE gel-based inks (85% by volume of oil) with improved 3D printing performance were prepared by using pea protein-inulin complexes as emulsifiers. In addition, the effects of oil type (corn, sunflower, flaxseed, or olive oil) on the 3D printing property, rheological properties, and microstructure of the HIPE gels was analyzed since different oils have different nutritional and physicochemical properties. Moreover, International Dysphagia Diet Standardization Initiative (IDDSI) foods created by 3D printing with these edible inks were evaluated in a population of the elderly suffering from dysphagia. It was found that HIPE-based edible inks containing an optimized inulin level (0.75% w/v) had the best 3D printing properties. In terms of oil type, the edible inks formulated from corn oil and from flaxseed oil had the best 3D printing property. As analyzed in the Lissajous plot, the addition of inulin remarkably improved the viscoelasticity of the inks, which improved their 3D printing property. These inks also exhibited high thixotropic recovery and good thermal stability. Moreover, cryo-SEM analysis showed that the PPI-inulin complex formed a barrier on the oil droplets' surface and a dense cross-linked structure between the particles. The IDDSI evaluation found that the HIPE gel inks were able to satisfy the requirements of Class IV and V foods in the IDDSI framework and could be classified as transitional foods, which would satisfy the food needs of patients with dysphagia.

Hydrogels for Lubrication: Synthesis, Properties, Mechanism, and Challenges

Hydrogels have received extensive attention as functional lubricants because of their excellent anti-friction and anti-wear properties, tunable tribological performances, and effectiveness in alleviating lubrication failures caused by the creeping or leakage of conventional liquid lubricants owing to their semi-solid nature. This review summarizes the current research advances in hydrogel lubricants fabricated with various organic and/or inorganic gelators, including organic polymeric or supramolecular hydrogels, inorganic particles-based hydrogels, and organic polymer-inorganic particle hybrid hydrogels. We illustrate not only the design strategies for constructing high-performance hydrogel lubricants but also the tribological behavior and mechanism of different types of hydrogel lubricants and their potential applications in industrial and biomimetic fields. Corresponding outlooks and suggestions for future studies have also been proposed.

Ensuring the quality of 3D printed medicines: Integrating a balance into a pharmaceutical printer for in-line uniformity of mass testing

Semi-solid extrusion (SSE) 3D printing has great potential to be integrated in a clinical setting, with the use of pre-filled and disposable pharma-ink syringes meeting regulatory good manufacturing practice (GMP) requirements. Uniformity of mass testing is a critical quality attribute and is carried out by weighing a specific amount of dosage units in a single batch and finding the average mass to evaluate any deviations. However, this test for small batches of 3D printed medicines may require weighing the entire manufactured batch. To overcome this limitation, an in-line analytical balance was implemented inside a GMP pharmaceutical 3D printer, with a specialised software-controlled weighing system for the automated mass uniformity testing of the entire printed batch. Three different dose batches (n = 28) of hydrocortisone pharma-ink were 3D printed and subjected to in-line mass uniformity testing. The developed software was capable of registering the weights of all individual printlets and accurately detecting any deviations within the accepted limits. Only one printlet was outside the accepted weight range, a result of the first print often being imperfect due to the semi-solid nature of the pharma-ink. The weight results were compared against an external analytical balance, and no significant differences were found. This study is the first to integrate an analytical balance inside a pharmaceutical printer, automating the dosage form mass uniformity testing which can save time, labour, and resources, whilst improving the quality control testing of 3D printed pharmaceuticals.

Structural characterization of tin in toothpaste by dynamic nuclear polarization enhanced 119Sn solid-state NMR spectroscopy

Stannous fluoride (SnF2) is an effective fluoride source and antimicrobial agent that is widely used in commercial toothpaste formulations. The antimicrobial activity of SnF2 is partly attributed to the presence of Sn(II) ions. However, it is challenging to directly determine the Sn speciation and oxidation state within commercially available toothpaste products due to the low weight loading of SnF2 (0.454 wt% SnF2, 0.34 wt% Sn) and the amorphous, semi-solid nature of the toothpaste. Here, we show that dynamic nuclear polarization (DNP) enables 119Sn solid-state NMR experiments that can probe the Sn speciation within commercially available toothpaste. Solid-state NMR experiments on SnF2 and SnF4 show that 19F isotropic chemical shift and 119Sn chemical shift anisotropy (CSA) are highly sensitive to the Sn oxidation state. DNP-enhanced 119Sn magic-angle turning (MAT) 2D NMR spectra of toothpastes resolve Sn(II) and Sn(IV) by their 119Sn chemical shift tensor parameters. Fits of DNP-enhanced 1D 1H → 119Sn solid-state NMR spectra allow the populations of Sn(II) and Sn(IV) within the toothpastes to be estimated. This analysis reveals that three of the four commercially available toothpastes contained at least 80% Sn(II), whereas one of the toothpaste contained a significantly higher amount of Sn(IV).

Early steps of an alternative test meal for gastric emptying scintigraphy

Background/Aim. Gastric emptying (GE) scintigraphy provides a physiologic and noninvasive measurement of GE. Although GE scintigraphy has been standardized, preparing a meal is still complex and not practical in daily routine. The aim of the study was to prepare a simple, practical, and easily standardizable semisolid meal and investigate its role in estimating the GE function in of rabbits. Methods. In the first part of the study (basal condition), the mixture of the macroaggregated albumin (MAA) labeled with 37 MBq (1 mCi) of technetium-99m (99mTc) and 40 g of barium sulfate (1g/mL) was applied to animals via a nasogastric catheter. A series of images (frame/min, 60 min) in the anterior and posterior projections were dynamically acquired, and the motion was corrected after the radiopharmaceutical application. A few days later, the same rabbits were scanned under the same protocol after a 1 mg atropine injection to simulate gastroparesis condition. Eleven rabbits were included according to inclusion and exclusion criteria, and a total of twenty-two imaging data sets were analyzed for quantification. Results. In the basal study, total counts of the mixture decreased from 87,800.83 ? 12,622.76 to 42,733.14 ? 6,591.53 at 30 min and to 13,684.19 ? 1,774.90 at 60 min, and these decreases were statistically significant (p = 0.003). Emptying percentages were 51.39 ? 0.78% at 30 min and 84.32 ? 1.56 at 60 min and were statistically significant (p = 0.003). After intravascular atropine sulfate injection, total counts of the mixture decreased from 84,508.78 ? 11,871.48 to 64,995.18 ? 9,298 at 30 min and to 53,507.17 ? 7,258.98 at 60 min, and these decreases were statistically significant (p = 0.003). Emptying percentages were 23.10 ? 1.11% at 30 min and 36.63 ? 1.42 at 60 min and were statistically significant (p = 0.003). The difference between basal and post-atropine sulfate gastric emptying percentage at 30th (p = 0.003) and 60th (p = 0.003) min was statistically significant. Conclusion. The meal, used in this study, is non-nutrient, fatty-free, and semisolid and is easy to prepare and administer. Due to its semisolid nature, it offers a chance to evaluate the quantification of regional and total GE as well as the separate roles of the fundus and antrum.

Two-Dimensional Gas Chromatographic and Mass Spectrometric Characterization of Lipid-Rich Biological Matrices-Application to Human Cerumen (Earwax).

Earwax is a readily accessible biological matrix that has the potential to be used in disease diagnostics. However, its semisolid nature and high chemical complexity have hampered efforts to investigate its potential to reveal disease markers. This is because more conventional methods of analysis such as gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry yield unsatisfactory results due to the presence of many nonvolatile and/or coeluting compounds, which in some cases have very similar mass spectrometric profiles. In addition, these routine methods often require the sample to be saponified, which dramatically increases the complexity of the analysis and makes it difficult to determine which compounds are actually present versus those that are produced by saponification. In this study, two-dimensional GC mass spectrometry (GC × GC–MS) was successfully applied for the characterization of the chemical components of earwax from healthy donors using nonpolar (primary) and midpolar (secondary) columns without saponification. Over 35 of the compounds that were identified are reported for the first time to be detected in unsaponified earwax. The resulting GC × GC–MS contour plots revealed visually recognizable compound class clusters of previously reported groups including alkanes, alkenes, fatty acids, esters, triglycerides, and cholesterol esters, as well as cholesterol and squalene. The application of GC × GC–MS revealed results that provide a foundation upon which future studies aimed at comparing healthy donor earwax to that from individuals exhibiting various disease states can be accomplished.

An experimental investigation of grease lubricated EHD contact subjected to normal sinusoidally variable loading

Oil lubrication of the contacts between high-elastic modulus, non-conformal surfaces is well understood in fully-flooded, steady state conditions, when there is generous supply of lubricant in the inlet and the parameters that govern the film thickness or the friction force do not vary in time. Semi-analytical or full numerical formulas have been derived which can predict the lubricant film thickness in terms of the working parameters and the properties of the materials involved. In case of lubricating greases, their semi-solid nature given by the presence of a solid phase makes the prediction of the film thickness and thus the design of various systems difficult. The equations developed for oil lubricants can be used, using the properties of the base oil however it was found experimentally that the actual film thickness deviates strongly from theoretical values, for values of the entrainment speed above a certain critical value. Grease-lubricated contacts are very important because over 90% of the second most numerous machine components that is, the rolling element bearings are lubricated with greases. An added factor of uncertainty is the variable load on the contacts between the rolling elements and the raceways, due to on one hand the passage of the former through the loaded region of the bearing and on the other due to vibrations likely to be experienced by the bearing. In this paper film thickness measurements of grease lubricated EHD contacts subjected to harmonic load variation are reported for the first time. The experiments were carried in a test rig based on optical interferometry under both steady-state and variable loading conditions. It was found that severely starved contacts, which run under very thin films, show a degree of recovery of the film thickness towards fully flooded values, depending of the frequency of the variable load and the properties of the grease.

Addition Of Sauce Enhances Finger-Snack Intake Among Japanese Elderly People With Dementia.

PurposeThe previous study demonstrated that the addition of a sauce is an effective means of influencing the consumption of finger foods among French elderly people with dementia. However, it is unclear the relative importance of low-level sensory factors such as flavor and a semi-solid nature and high-level cognitive factors such as memory stimulation and familiarity to the effect of the addition of sauce on food intake. The present study investigated whether the addition of sauce affects finger-snack intake among Japanese elderly people with dementia who were not familiar with sauce dipping.Patients And MethodsA total of 21 patients with dementia who were recruited in a nursing home in Tokyo received a plate of cut baumkuchen (a very thinly layered German roll cake), which had pieces of baumkuchen both with and without sauce, at their afternoon snack time. The amount of food intake and the first choice between options were measured for each participant. We used chocolate (in Experiment 1, n = 21) and agave (Experiment 2, n =14) syrups as sauce samples.ResultsResults of both experiments demonstrate that snack consumption was greater for the with-sauce options than for the without-sauce options. A 90.5% of the participants in Experiment 1 and 64.3% of participants in Experiment 2 ate more snacks with sauce than without sauce.ConclusionThese findings imply that low-level sensory factors such as flavor and a semi-solid nature contribute relatively more strongly to the enhancement of food consumption with the addition of sauce than do high-level cognitive factors such as memory stimulation and familiarity, because Japanese elderly people are not always familiar with the custom of wiping up the sauce with food.

The effects of Fenton process on the removal of petroleum hydrocarbons from oily sludge in Shiraz oil refinery, Iran

BackgroundDue to the high concentrations of total petroleum hydrocarbons (TPH) in oily sludge and their environmental hazards, the concern regarding their effects on health and the environment has increased. The main objective of this research was focused on evaluating the feasibility of using Fenton process in removing TPH in oily sludge from Shiraz oil refinery, Southern Iran.ResultsTo determine optimum conditions, four different parameters were assessed at four different levels using Taguchi method. According to data, the optimum conditions were as follows: the reaction time of 1 hour, H2O2 to sample mass ratio of 15, H2O2 to Fe (II) molar ratio of 10 and pH of 5. The maximum TPH reduction rate was 36.47%. Because of the semi-solid nature of the sample and the hydroxyl radicals mainly generated in the aqueous solution, TPH reduction rate greatly improved by adding water. Ultimately, by adding 40 ml water per gram of the oily sludge under optimized conditions, the reduction rate of 73.07% was achieved.ConclusionsThe results demonstrated that this method can be used as a pre-treatment method for the oily sludge. Moreover, a complementary treatment is necessary to reach the standard limit.

Atherosclerotic plaque characterization by NMR spectroscopy

Background: High resolution Magnetic Resonance Spectroscopy (MRS) in vitro was used to investigate the correlation between the chemical composition of atheromatous plaques and their stability (vulnerability to rupture) which is of fundamental importance and is a rather controversial point in literature. Methods: In this study five tissues were collected from ex vivo human abdominal aortas and divided in three groups according to their atherosclerotic lesion using the American Heart Association Committee on Vascular Lesions. Due to the semi-solid nature of the plaques, Magic Angle Spinning (MAS) and heteronuclear Decoupling (DEC) were used to acquire six 13 C spectra with appreciable high resolution for five samples and the solvent. The 1 H high resolution spectra also were obtained for the same samples. Results: The most common fatty acids present in the samples were identified and also the relative amounts of polyunsaturated (PUFA), unsaturated (UFA) and saturated fatty acids associated with the progress of the deterioration process of atheromatous plaques. Conclusions: NMR results show that the lipidic composition of atheromatous plaque evolves from a state with high levels of PUFA and UFA for a subject with lower classification to a new state containing, 6 and 4 times less unsaturated fatty acids respectively than those subjects with more stenotic lesions. In addition, average rate of conversion of PUFA to UFA is approximately two times higher in more stenotic lesions. These results suggest that the lipidic components of atheromatous plaque can be related to its vulnerability to rupture, which clearly demonstrate the importance of the method to study this disease.

Evaluation of accelerated stability test conditions for medicated chewing gums

The overall stability of medicated chewing gums is investigated under different storage conditions. Active substances with different chemical stabilities in solid state are chosen as model drugs. The dosage form is a three layer tablet obtained by direct compression. The gum core contains the active ingredient while the external layers are formulated to prevent gum adhesion to the punches of the tableting machine. Two accelerated test conditions (40°C/75% RH and 30°C/65% RH) are performed for 6 months. Furthermore, a long-term stability test at room conditions is conducted to verify the predictability of the results obtained from the stress tests. Some drugs are stable in all the conditions tested, but other drugs, generally considered stable in solid dosage forms, have shown relevant stability problems particularly when stress test conditions are applied to this particular semi-solid dosage forms. For less stable drugs, the stress conditions of 40°C/75% RH are not always predictable of chewing gum stability at room temperature and may produce false negative; intermediate conditions, 30°C/65% RH, are more predictive for this purpose, the results of drug content found after 6 months at intermediate stress conditions and 12 months at room conditions are generally comparable. But the results obtained show that only long-term conditions stability tests gave consistent results. During aging, the semi solid nature of the gum base itself, may also influence the drug delivery rate during chewing and great attention should be given also to the dissolution stability.

Use of calcium hydroxylapatite (Radiesse<sup>®</sup>) for facial augmentation

Radiesse (Bioform Inc, USA) is a sterile, latex-free, non-pyrogenic, semi-solid, cohesive subdermal, injectable implant, whose principal component is synthetic calcium hydroxylapatite, a biocompatible material with over 20 years of use in medicine. The semi-solid nature of the product is created by suspending calcium hydroxylapatite microspheres of 25-45 microns diameter in a gel carrier of carboxymethylcellulose. The product has FDA approval for esthetic facial augmentation in the US. Such approval includes the long-lasting correction of moderate to severe facial wrinkles and folds and the treatment of facial fat loss due to immunodeficiency virus infection. Diverse facial regions can be injected in order to ameliorate or enhance some features: glabellar lines, subdermal support of the brows, malar and buccal fat pads, tear troughs, nasolabial folds, nose, lips, perioral region, marionette lines, oral commisures and chin among others, as well as saucerized acne scars. Other medical indications include nipple projection for nipple areolar reconstruction, urinary incontinence, vesicoureteral reflux, vocal cord augmentation, and use as a radiographic tissue marker. The average lasting result is from 12 to 18 months. Radiesse can be considered an effective soft-tissue filler for overall longevity, biocompatibility, and low rate of side effects.

Mucoadhesive, syringeable drug delivery systems for controlled application of metronidazole to the periodontal pocket: In vitro release kinetics, syringeability, mechanical and mucoadhesive properties

Novel mucoadhesive formulations containing hydroxyethylcellulose (HEC; 3 and 5%, w/w) or Carbopol (3 and 5%, w/w), polycarbophil (PC; 1 and 3%, w/w) and metronidazole (5%, w/w) at pH 6.8 were designed for the treatment of periodontal diseases. Each formulation was characterised in terms of hardness, compressibility, adhesiveness and cohesiveness (using Texture Profile Analysis), drug release, adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode) and, finally, syringeability (using the texture analyser in compression mode). Drug release from all formulations was non-diffusion controlled. Drug release was significantly decreased as the concentration of each polymeric component was increased, due to both the concomitant increased viscosity of the formulations and, additionally, the swelling kinetics of PC following contact with dissolution fluid. Increasing the concentrations of each polymeric component significantly increased formulation hardness, compressibility, adhesiveness, mucoadhesion and syringeability, yet decreased cohesiveness. Increased product hardness, compressibilty and syringeability were due to polymeric effects on formulation viscosity. The effects on cohesiveness may be explained both by increased viscosity and also by the increasing semi-solid nature of products containing 5% HEC or Carbopol and PC (1 or 3%). The observations concerning formulation adhesiveness/mucoadhesion illustrate the adhesive nature of each polymeric component. Greatest adhesion was noted in formulations where neutralisation of PC was maximally suppressed. For the most part, increased time of contact between formulation and mucin significantly increased the required force of detachment, due to the greater extent of mucin polymer hydration and interpenetration with the formulations. Significant statistical interactions were observed between the effects of each polymer on drug release and mechanical/mucoadhesive properties. These interactions may be explained by formulatory effects on the extent of swelling of PC. In conclusion, the formulations described offered a wide range of mechanical and drug release characteristics. Formulations containing HEC exhibited superior physical characteristics for improved drug delivery to the periodontal pocket and are now the subject of long-term clinical investigations.

Texture profile analysis of bioadhesive polymeric semisolids: Mechanical characterization and investigation of interactions between formulation components

This study reports the use of texture profile analysis (TPA) to mechanically characterize polymeric, pharmaceutical semisolids containing at least one bioadhesive polymer and to determine interactions between formulation components. The hardness, adhesiveness, force per unit time required for compression (compressibility), and elasticity of polymeric, pharmaceutical semisolids containing polycarbophil (1 or 5% w/w), polyvinylpyrrolidone (3 or 5% w/w), and hydroxyethylcellulose (3, 5, or 10% w/w) in phosphate buffer (pH 6.8) were determined using a texture analyzer in the TPA mode (compression depth 15 mm, compression rate 8 mm s−1, 15 s delay period). Increasing concentrations of polycarbophil, polyvinylpyrrolidone, and hydroxyethylcellulose significantly increased product hardness, adhesiveness, and compressibility but decreased product elasticity. Statistically, interactions between polymeric formulation components were observed within the experimental design and were probably due to relative differences in the physical states of polyvinylpyrrolidone and polycarbophil in the formulations, i.e., dispersed/dissolved and unswollen/swollen, respectively. Increased product hardness and compressibility were possibly due to the effects of hydroxyethylcellulose, polyvinylpyrrolidone, and polycarbophil on the viscosity of the formulations. Increased adhesiveness was related to the concentration and, more importantly, to the physical state of polycarbophil. Decreased product elasticity was due to the increased semisolid nature of the product. TPA is a rapid, straightforward analytical technique that may be applied to the mechanical characterization of polymeric, pharmaceutical semisolids. It provides a convenient means to rapidly identify physicochemical interactions between formulation components. © 1996 John Wiley & Sons, Inc.

Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases.

This study examined the mechanical characteristics and release of tetracycline from bioadhesive, semi-solid systems which were designed for the treatment of periodontal diseases. Tetracycline release into phosphate buffered saline (pH 6.8, 0.03 M) was examined using a Caleva 7ST dissolution apparatus at 37 degrees C. The mechanical properties of each formulation (hardness, compressibility, adhesiveness, elasticity and cohesiveness) were determined using texture profile analysis. Syringeability was measured using the texture analyser in compression mode as the work of syringeability i.e. the force required to express the product from a periodontal syringe over a defined distance. Tetracycline release from all formulations was zero-order for 24-54 h and ranged from 1.59 +/- 0.20 to 15.80 +/- 0.50 mg h-1. Increased concentrations of hydroxyethylcellulose (HEC) decreased the rate of release of tetracycline, due to the concomitant increase in product viscosity and the subsequent decreased rate of penetration of dissolution fluid into the formulation. Conversely, an increased polyvinylpyrrolidone (PVP) concentration increased tetracycline release rates, due to an increased formulation porosity following dissolution of this polymer. Increased concentrations of HEC and PVP increased the hardness, compressibility and work of syringeability of the semi-solid formulations, due to increased product viscosity. An increase in formulation adhesiveness, a parameter related to bioadhesion, was observed as the concentrations of HEC and PVP were increased, illustrating the adhesive nature of these polymers. Increased concentrations of HEC and PVP enhanced the semi-solid nature of the product, resulting in decreased product elasticity and cohesiveness. Several statistically significant interactions between polymeric formulation components were observed within the factorial design, with respect to rate of release and all mechanical properties. These interactions arose because of variations in the physical states (dissolved or dispersed) of polymeric formulation components. The optimal choice of bioadhesive formulation for use in periodontal disease will involve a compromise between achieving the necessary release rate of tetracycline and the mechanical characteristics of the formulation, as these factors will affect clinical efficacy and the ease of product application into the periodontal pocket.

Semi-solid hydrophobic bioerodible poly (ortho ester) for potential application in glaucoma filtering surgery

A semi-solid poly(ortho ester) was prepared by the reaction between 1,2,6-hexanetriol and trimethyl orthoacetate. The use of a flexible triol such as 1,2,6-hexanetriol produces highly flexible polymers that have viscous behavior at room temperature. The semi-solid nature of the polymer allows the incorporation of therapeutic agents by a simple mixing procedure without the need to use solvents or elevated temperatures. The release of 5-fluorouracil (5-FU) from this semi-solid polymer was studied in vitro. The rate of drug release was controlled by changing the molecular weight and indirectly the viscosity of the polymers. Polymers with 3500, 5800, 10100, 15200, 33300 Da molecular weight were synthesized. Drug release ranging from one day for the 3500 Da to 7 days for the 33300 Da molecular weight polymer was obtained. The different procedures used to modulate the polymer molecular weight during the synthesis are described. The temperature effect on the drug loaded polymer was also studied. The results have shown that the polymer rheological properties and the 5-FU release were affected by this parameter. The rheological study has shown that the viscosity decreased with increasing temperature. In the same way, the dependence between the temperature and the drug release was shown by the fact that only 40 wt% of 5-FU was released from the 33300 Da poly (ortho ester) after 11 days at room temperature. The possibility of injecting this polymer under the conjunctiva in the glaucoma filtering surgery therapy using a hypodermic syringe was discussed in order to carry out in vivo 5-FU release studies.