methylcellulose and stearic-acid

Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.

Topics: Adult; Calorimetry, Differential Scanning; Chemical Phenomena; Clonidine; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Excipients; Gastrointestinal Agents; Gastrointestinal Transit; Humans; Hypromellose Derivatives; Kinetics; Male; Methylcellulose; Parasympatholytics; Sodium Bicarbonate; Solubility; Stearic Acids; Tablets; Young Adult

Cryogenic transmission electron microscopy of high-pressure freezing (HPF) samples is a well-established technique for the analysis of liquid containing specimens. This technique enables observation without removing water or other volatile components. The HPF technique is less used in scanning electron microscopy (SEM) due to the lack of a suitable HPF specimen carrier adapter. The traditional SEM cryotransfer system (PP3000T Quorum Laughton, East Sussex, UK; Alto Gatan, Pleasanton, CA, USA) usually uses nitrogen slush. Unfortunately, and unlike HPF, nitrogen slush produces water crystal artefacts. So, we propose a new HPF specimen carrier adapter for sample transfer from HPF system to cryogenic-scanning electronic microscope (Cryo-SEM). The new transfer system is validated using technical two applications, a stearic acid in hydroxypropyl methylcellulose solution and mice myocardium. Preservation of samples is suitable in both cases. Cryo-SEM examination of HPF samples enables a good correlation between acid stearic liquid concentration and acid stearic occupation surface (only for homogeneous solution). For biological samples as myocardium, cytoplasmic structures of cardiomyocyte are easily recognized with adequate preservation of organelle contacts and inner cell organization. We expect this new HPF specimen carrier adapter would enable more SEM-studies using HPF.

Topics: Animals; Cellulose; Cryoelectron Microscopy; Cryopreservation; Freezing; Male; Methylcellulose; Mice; Mice, Inbred C57BL; Myocardium; Polymers; Pressure; Software; Specimen Handling; Stearic Acids

The effects of ultrasound treatment (UT) on the properties of methylcellulose (MC)/stearic acid (SA) blending films were studied. Film-forming emulsions were prepared with different UT conditions and characterized with respect to viscosity. The lipid aggregation and distribution in the blending dispersions were studied by the micrographs of Transmission Electron Microscopy (TEM). The micrographs of both surface and cross-section of the films were observed by scanning electron microscope (SEM) and the tensile strength (TS), elongation at break (E), water vapor permeability (WVP) and contact angles of the resulting films were determined as well. The intensification of the UT condition led to a decrease of viscosity of the MC-SA blending emulsions, a more homogeneous lipid distribution and a denser internal microstructure of the resulting films. UT exposure affected the mechanical, moisture barrier and surface hydrophobic properties. The optimal values of both TS and E was obtained from the sample treated for 10min and 180W power, while the sample treated for 10min and 270W presented the lowest value of WVP. However, an excessive exposure of UT led to a decrease of the mechanical and moisture barrier performance. By observing and analyzing the SEM graphs and the contact angles of the film surfaces, it was found that UT within the appropriate bounds had a notably positive effect on improving the surface hydrophobic property of the MC-SA blending films.

Topics: Emulsions; Lipids; Methylcellulose; Microscopy, Electron, Transmission; Permeability; Rheology; Steam; Stearic Acids; Ultrasonics; Viscosity

The influence of different additives on the mechanical properties of hydroxypropyl methylcellulose (HPMC) free films was studied using tensile testing. Free films were prepared using the cast method and sliced into bands, and their tensile strength and maximal elongation at break was measured. The results showed that the addition of PEG 400 and polysorbate 80 into the coating formulation had the most influence on the films' mechanical properties compared to the HPMC film used as a control. Tablet cores composed of microcrystalline cellulose and lactose with and without Mg stearate and compressed at three different compression forces were tested for wettability with coating formulations containing PEG 400 and polysorbate 80. For formulations with no Mg stearate added, the contact angle decreased with increasing core hardness and it also coincided with greater adhesion force of the coating. The addition of Mg stearate in the core led to reduced adhesion of the film coating with PEG 400, whereas the influence on the adhesion force of the film coating containing polysorbate 80 was negligible. The results also show that the adhesion force, regardless of the tablet core formulation, is highest at medium core hardness.

Topics: Adhesiveness; Chemistry, Pharmaceutical; Excipients; Hardness; Hypromellose Derivatives; Methylcellulose; Plasticizers; Porosity; Solubility; Stearic Acids; Tablets; Tensile Strength

The present work explores the application of in situ near infrared (NIR) imaging to determine the drug release mechanisms from hydrophilic matrices containing a low solubility model drug (Compound A, with aqueous solubility at 37°C ∼0.05 mg/mL). Correlation maps generated from the NIR data determined the extent drug and HPMC co-localisation. Judicious thresholding facilitated band separation of low drug/HPMC ratio and high drug/HPMC ratio. A pseudo-image time-series confirmed the dominant erosion release mechanisms. The gel layer region showed low drug concentration with progressive dissolution. However, large drug aggregates remained unchanged even when fully "immersed" within the gel layer. From the correlation maps, further discrimination was possible for the pure drug signal, generating a highly contrasted image that enabled individual particle tracking. These contrasted images also revealed the evolution of single or clusters of drug particles. Initially, an aggregative process involving the drug particles occurred, with a subsequent migration process of such particles. This second process dominated the subsequent 90 min before significant erosion. In summary, this study has provided tentative confirmation that NIR imaging has the potential to afford insights into drug liberation phenomena where erosion is the predominant release mechanism.

Topics: Cellulose; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Lactose; Methylcellulose; Pharmaceutical Preparations; Spectroscopy, Near-Infrared; Stearic Acids; Tablets; Water

Gastric retention is postulated as an approach to improve bioavailability of compounds with narrow absorption windows. To elucidate the role of image size on gastric retention and pharmacokinetics, formulations with different image sizes and swelling kinetics but similar dissolution rates were designed and imaged in dogs. Diet had a clear effect, with increasing calorific intake prolonging retention in the dog model. In contrast to clinical observations, no obvious effect of image size on gastric retention was observed in the dog, with the larger gastric retentive (GR) and smaller controlled release (CR) formulations both demonstrating similar gastric emptying. Comparable pharmacokinetic profiles were observed for the two formulations, corroborating the imaging data and providing evidence of similar in vivo dissolution rates and dosage form integrity in the dog. Food, specifically meal composition, resulted in comparable enhancements in exposure in the dog and clinic due to prolonged gastric retention. However, differentiating retention based on image size in the dog was not feasible due to the smaller pyloric aperture compared to humans. This work illustrates that the dog is capable of determining the pharmacokinetic advantage of gastric retention relative to immediate release (IR) or CR formulations, however, has limited value in differentiating between CR and GR formulations.

Topics: Animals; Barium; Biological Availability; Cellulose; Delayed-Action Preparations; Diagnostic Imaging; Dogs; Drug Compounding; Energy Intake; Fasting; Food-Drug Interactions; Gastric Emptying; Hypromellose Derivatives; Lactose; Male; Metformin; Methylcellulose; Solubility; Stearic Acids

Oral bioavailability of atorvastatin calcium (ATC) is very low (only 14%) due to instability and incomplete intestinal absorption and/or extensive gut wall extraction. When ATC is packed in the form of tablets, powders, etc., it gets destabilized as it is exposed to the oxidative environment, which is usually present during the production process, the storage of the substance, and the pharmaceutical formulation. Therefore, stabilized gastro-retentive floating tablets of ATC were prepared to enhance bioavailability. Water sorption and viscosity measurement studies are performed to get the best polymer matrix for gastro-retention. A 3(2) factorial design used to prepare optimized formulation of ATC. The selected excipients such as docusate sodium enhanced the stability and solubility of ATC in gastric media and tablet dosage form. The best formulation (F4) consisting of hypromellose, sodium bicarbonate, polyethylene oxide, docusate sodium, mannitol, crosscarmellose sodium, and magnesium stearate, gave floating lag time of 56 ± 4.16 s and good matrix integrity with in vitro dissolution of 98.2% in 12 h. After stability studies, no significant change was observed in stability, solubility, floating lag time, total floating duration, matrix integrity, and sustained drug release rates, as confirmed by DSC and powder X-ray diffraction studies. In vivo pharmacokinetic study performed in rabbits revealed enhanced bioavailability of F4 floating tablets, about 1.6 times compared with that of the conventional tablet (Storvas® 80 mg tablet). These results suggest that the gastric resident formulation is a promising approach for the oral delivery of ATC for improving bioavailability.

Topics: Administration, Oral; Animals; Atorvastatin; Biological Availability; Calorimetry, Differential Scanning; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dioctyl Sulfosuccinic Acid; Drug Compounding; Drug Stability; Excipients; Female; Gastric Mucosa; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypromellose Derivatives; Male; Mannitol; Methylcellulose; Polyethylene Glycols; Powder Diffraction; Pyrroles; Rabbits; Regression Analysis; Sodium Bicarbonate; Solubility; Stearic Acids; Tablets; Technology, Pharmaceutical; Viscosity; Water; X-Ray Diffraction

Formulation of layered pellets can be a useful method for the preparation of multiparticulate systems. The aims of this work were to study the properties of hydrophilic active agent (pirenzepine dihydrochloride) layers formed on different pellet cores, the efficacy of layering and the connection between the core and the layers. The carrier pellets were prepared from mixtures of a hydrophilic (microcrystalline cellulose) and a hydrophobic (magnesium stearate) component in different ratios. These cores were coated in a fluid bed apparatus with an aqueous solution of active agent, with or without the addition of hydroxypropyl methyl cellulose (HPMC) as an adhesive component. The wettability of the pharmaceutical powders was assessed by means of Enslin number and contact angle measurements, and the surface energy was determined. Spreading coefficients of the components were also calculated and correlated with pellet properties such as the content of active agent, the friability and the morphological appearance of the layered product. An increased friability of the layer formed and the lower effectiveness of the process were experienced with a reduction in the wetting of the core. The efficiency of layering on a less polar core could be increased by the addition of HPMC, but the sensitivity of these pirenzepine layers to mechanical stress was higher. The type of the abrasion of these particles was dissimilar to that for samples prepared without HPMC. Peeling of the layers containing HPMC was observed for hydrophobic cores, but this phenomenon was not detected for the hydrophilic ones. These results can be explained by the spreading coefficients, which revealed an insufficient adhesion of layers for the samples that exhibited peeling.

Topics: Cellulose; Chemistry, Pharmaceutical; Drug Carriers; Drug Implants; Hardness; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Methylcellulose; Particle Size; Physical Phenomena; Pirenzepine; Solubility; Stearic Acids; Surface Properties; Thermodynamics; Wettability

This study optimizes the composition of an effervescent floating tablet (EFT) containing metformin hydrochloride (M) regarding tablet hardness (H), time to dissolve 60% of the embedded drug (t60%), and buoyancy, the floating lag time (FLT). A simplex lattice experimental design has been used comprising different levels of hydroxypropylmethylcellulose (HPMC), stearic acid (SA), sodium bicarbonate (SB) as tablet matrix components, and hardness (H), t60%, FLT as response variables. Two models have been applied to decide which composition will result in Fickian diffusion or in overlapping of two dissolution mechanisms, diffusion and matrix erosion. Three of EFT showed the two dissolution mechanisms but most of EFT showed Fickian diffusion only. Checking the experimental response by a linear, quadratic, special cubic and cubic model using multivariate regression analysis resulted in best fit for the cubic model. Overlaying the results for the cubic model under constraints defined shows the domain of accepted values of response variables. The optimized EFT shall have been included HPMC between 15.6% and 24.2%, SA between 12.8 and 15.6% and SB between 16.1% and 17.5%. The result of this study has been critically evaluated considering analogous EFT described in literature.

Topics: Calorimetry, Differential Scanning; Drug Compounding; Excipients; Hardness Tests; Hypoglycemic Agents; Hypromellose Derivatives; Kinetics; Lactose; Metformin; Methylcellulose; Powders; Regression Analysis; Solubility; Spectrophotometry, Ultraviolet; Stearic Acids; Tablets

Edible composite coatings based on hydroxypropyl methylcellulose (HPMC), hydrophobic components (beeswax and shellac), and food preservatives with antifungal properties were evaluated on "Ortanique" mandarins during long-term cold storage. Selected food preservatives included potassium sorbate (PS), sodium benzoate (SB), sodium propionate (SP), and their mixtures. Intact mandarins or mandarins artificially inoculated with the pathogens Penicillium digitatum and Penicillium italicum, the causal agents of citrus postharvest green (GM) and blue (BM) molds, respectively, were coated and stored up to 8 wk at 5 °C + 1 wk of shelf-life at 20 °C. HPMC-lipid coatings containing food preservatives controlled better GM than BM on Ortanique mandarins. SB- and SB + SP-based coatings reduced the incidence of GM by about 35% after 4 wk at 5 °C. Among all coatings, only the SB-based coating reduced the incidence of GM (about 16%) after 6 wk at 5 °C. All coatings significantly reduced disease severity of both GM and BM after 6 wk at 5 °C. Analytical and sensory fruit quality was evaluated on intact mandarins. All coatings, especially the SB + SP-based coatings, were effective to control weight loss and maintain the firmness of coated mandarins. Internal gas concentration, juice ethanol and acetaldehyde content, sensory flavor, off-flavor, and fruit appearance were not adversely affected by the application of the antifungal coatings. Further studies should focus on the modification of some physical characteristics of the coatings to improve the gloss and visual aspect of treated mandarins.

Topics: Adult; Antifungal Agents; Chemical Phenomena; Citrus; Female; Food Handling; Food Preservatives; Fruit; Glycerol; Humans; Hypromellose Derivatives; Male; Methylcellulose; Middle Aged; Penicillium; Propionates; Quality Control; Sensation; Sodium Benzoate; Sorbic Acid; Stearic Acids; Surface Properties; Temperature

Bilayered tablets of Divalproex sodium for once-a-day administration were prepared using a hydrophilic and hydrophobic polymer as release retarding agents. This technology was found to be more effective than a simple matrix tablet with a mixture of the above polymers in order to retard the drug release for a period of 24 h. The drug release profile was strongly dependent on the presence of wicking agent, pathlength of hydrophobic layer, and hardness of tablet. f(1) value of 6.92 and f(2) value of 76.72 indicated similarity between the release profiles of batch BT3 and reference tablet (Depakote((R)) ER) with the target release of over 55% within 12 h and over 85% within 18 h. Mathematical modeling using Korsmeyer-Peppas equation indicated that the release followed a combination of diffusion and erosion mechanism.

Topics: Biological Availability; Cellulose; Delayed-Action Preparations; Excipients; Fatty Alcohols; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Biological; Silicon Dioxide; Starch; Stearic Acids; Tablets; Valproic Acid

The purpose of this research work was to develop venlafaxine hydrochloride-coated and layered matrix tablets using hypromellose adopting wet granulation technique. The granules and the tablets were characterized. The monolithic tablets were coated with different ratios of ethyl cellulose and hypromellose. The in vitro dissolution study was performed in distilled water. In the layered tablets, the middle layer containing drug was covered with barrier layers containing high viscosity grade hypromellose. Simplex lattice design was used for formulating the layered tablets. The dissolution study of the optimized batches and a reference product was carried out in 0.1 N HCl, phosphate buffer and hydroalcoholic solution. Burst drug release was exhibited by the uncoated tablets, probably due to high aqueous solubility of venlafaxine HCl. The coated tablets showed sustained drug release without burst effect. The drug release was best explained by Weibull model. A unified Weibull equation was evolved to express drug release from the coated tablets. The layered tablets also exhibited sustained release without burst effect due to effective area reduction. The optimized batches showed identical drug release in 0.1 N HCl, phosphate buffer and 10% v/v aqueous alcohol. Layered tablets may well be adopted by the industry due to the possibility of achieving a high production rate.

Topics: Algorithms; Antidepressive Agents, Second-Generation; Biological Availability; Cellulose; Chemistry, Pharmaceutical; Cyclohexanols; Delayed-Action Preparations; Drug Stability; Ethanol; Excipients; Hypromellose Derivatives; Lactose; Methylcellulose; Models, Chemical; Models, Statistical; Stearic Acids; Tablets, Enteric-Coated; Venlafaxine Hydrochloride; Water

The objective of this work was to investigate the effect of fatty acid (FA) type and content on mechanical properties, water vapor permeability and oxygen permeability of hydroxypropyl methycellulose (HPMC)-beeswax (BW) stand-alone edible films. The effect of these films formed as coatings on the postharvest quality of 'Ortanique' mandarins was also studied. Selected FAs were stearic acid (SA), palmitic acid (PA), and oleic acid (OA), using BW/FA ratios of 1:0.5 and 1:0.2 (w/w). HPMCBW coatings reduced weight and firmness loss of 'Ortanique' mandarins, without compromising flavor quality compared to uncoated mandarins. Coatings containing OA provided the best weight loss control at both concentrations tested; however, when the BW/OA ratio was 1:0.5, the coatings increased fruit internal CO2, ethanol, and acetaldehyde contents of 'Ortanique' mandarins, therefore reducing flavor compared to the rest of the coatings studied. Although barrier and mechanical properties might be used to understand coating performance, differences observed between film oxygen permeability and coating permeability indicate that permeance should be measured on the coated fruit.

Topics: Citrus sinensis; Fatty Acids; Food Packaging; Food Preservation; Fruit; Humans; Hypromellose Derivatives; Methylcellulose; Oleic Acid; Palmitic Acid; Quality Control; Sensation; Stearic Acids; Waxes

The purpose of this investigation was to prepare a gastroretentive drug delivery system of famotidine. Floating tablets of famotidine were prepared employing two different grades of methocel K100 and methocel K15M by effervescent technique; these grades of methocel were evaluated for their gel forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy and dissolution studies. The effect of citric acid on drug release profile and floating properties was investigated. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 6-10 hours. Decrease in the citric acid level increased the floating lag time but tablets floated for longer duration. A combination of sodium bicarbonate (130mg) and citric acid (10mg) was found to achieve optimum in vitro buoyancy. The tablets with methocel K100 were found to float for longer duration as compared with formulations containing methocel K15M. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed.

Topics: Anti-Ulcer Agents; Bioreactors; Carbon Dioxide; Chemistry, Pharmaceutical; Citric Acid; Drug Delivery Systems; Famotidine; Gels; Hardness; Hydrogen-Ion Concentration; Methylcellulose; Molecular Weight; Povidone; Reproducibility of Results; Rheology; Sodium Bicarbonate; Stearic Acids; Surface Properties; Tablets; Talc; Time Factors; Viscosity

Complex tablets with zero-order drug release characteristics were fabricated using three-dimensional printing processes. The matrix tablets exhibited material gradients in radial direction and had drug-free release-barrier layers on both bases. The content of model drug acetaminophen incorporated in the tablets through premixing reached up to 68% of the tablets' weight. Tablets with ethylcellulose gradients showed acceptable mechanical and pharmacotechnical properties, as indicated by crushing strength, friability, and content uniformity tests. The structure and the gradients of ethylcellulose in the tablets were envisaged through environmental scanning electron microscopy and fluorescence tracing technique. Erosion and dissolution studies in vitro indicated that drug was released via a two-dimensional surface erosion mechanism, and 98% of the drug could be released linearly in 12 h. Tablets with other release-retardation material gradients such as sodium lauryl sulfate, stearic acid, and Eudragit RS-100 showed similar release-retardation effects by different release-retardation mechanisms. Through the printing of release-retardation materials, 3DP processes could easily prepare tablets with high dosage and special design features for furnishing the desired drug release characteristics.

Topics: Acetaminophen; Acrylic Resins; Algorithms; Analgesics, Non-Narcotic; Cellulose; Delayed-Action Preparations; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Microscopy, Electron, Scanning; Particle Size; Sodium Dodecyl Sulfate; Solubility; Stearic Acids; Surface Properties; Surface-Active Agents; Tablets

The purpose of this study was to evaluate the change of surface roughness and the development of the film during the film coating process using laser profilometer roughness measurements, SEM imaging, and energy dispersive X-ray (EDX) analysis. Surface roughness and texture changes developing during the process of film coating tablets were studied by noncontact laser profilometry and scanning electron microscopy (SEM). An EDX analysis was used to monitor the magnesium stearate and titanium dioxide of the tablets. The tablet cores were film coated with aqueous hydroxypropyl methylcellulose, and the film coating was performed using an instrumented pilot-scale side-vented drum coater. The SEM images of the film-coated tablets showed that within the first 30 minutes, the surface of the tablet cores was completely covered with a thin film. The magnesium signal that was monitored by SEM-EDX disappeared after ~15 to 30 minutes, indicating that the tablet surface was homogeneously covered with film coating. The surface roughness started to increase from the beginning of the coating process, and the increase in the roughness broke off after 30 minutes of spraying. The results clearly showed that the surface roughness of the tablets increased until the film coating covered the whole surface area of the tablets, corresponding to a coating time period of 15 to 30 minutes (from the beginning of the spraying phase). Thereafter, the film only became thicker. The methods used in this study were applicable in the visualization of the changes caused by the film coating on the tablet surfaces.

Topics: Coated Materials, Biocompatible; Drug Compounding; Hypromellose Derivatives; Materials Testing; Membranes, Artificial; Methylcellulose; Stearic Acids; Surface Properties; Tablets; Titanium

To prepare composite films from biopolymers with anti-listerial activity and moisture barrier properties, the antimicrobial efficiency of chitosan-hydroxy propyl methyl cellulose (HPMC) films, chitosan-HPMC films associated with lipid, and chitosan-HPMC films chemically modified by cross-linking were evaluated. In addition, the physicochemical properties of composite films were evaluated to determine their potential for food applications. The incorporation of stearic acid into the composite chitosan-HPMC film formulation decreased water sensitivity such as initial solubility in water and water drop angle. Thus, cross-linking of composite chitosan-HPMC, using citric acid as the cross-linking agent, led to a 40% reduction in solubility in water. The water vapor transfer rate of HPMC film, approximately 270 g x m(-2) x day(-1) x atm(-1), was improved by incorporating chitosan and was further reduced 40% by the addition of stearic acid and/or cross-linking. Anti-listerial activity of films was determined on solid medium by a numeration technique. Chitosan-HPMC-based films, with and without stearic acid, inhibited the growth of Listeria monocytogenes completely. On the other hand, a loss of antimicrobial activity after chemical cross-linking modification was observed. FTIR and 13C NMR analyses were then conducted in order to study a potential chemical modification of biopolymers such as a chemical reaction with the amino group of chitosan. To complete the study, the mechanical properties of composite films were determined from tensile strength assays.

Topics: Anti-Infective Agents; Chitosan; Cross-Linking Reagents; Food Packaging; Hypromellose Derivatives; Listeria monocytogenes; Methylcellulose; Stearic Acids; Structure-Activity Relationship

The use of inverse gas chromatography to assess surface properties of a range of pharmaceutical powders was examined. The powders were two sources of hydroxy propylmethyl cellulose (HPMC), microcrystalline cellulose, magnesium stearate, and acyclovir. These were selected to cover a range for properties from amorphous to crystalline, hydrophilic to hydrophobic, and high to low aqueous solubility. It was found that many powders gave a similar value for the dispersive surface energy, which is surprising given the differences in chemical nature. It is likely that this is due to the use of infinite dilution giving rise to the study of specific regions of the powder surface only. The values obtained for dispersive energies were not influenced by packing mass or flow rate of the carrier gas. The retention of polar probes on the column was a concern for the amorphous HPMC samples. This gave rise to derived values for acid-base nature which varied depending on sample mass and carrier gas flow rate. The data show that care must be taken when studying amorphous samples for which it is possible to obtain diffusion into the material rather than just surface adsorption of probes. Despite these problems, it was still possible to differentiate between the samples (including differences between the two HPMC samples) by use of polar probes. It was also possible to see differences in absorption into the sample, reflecting the different physical forms. For example, microcrystalline cellulose behaved very differently to HPMC. It can be concluded that inverse gas chromatography is a valuable characterization tool, but it must be used with care especially with respect to polar probes on amorphous samples.

Topics: Acyclovir; Cellulose; Chemical Phenomena; Chemistry, Physical; Chromatography, Gas; Crystallization; Excipients; Hypromellose Derivatives; Methylcellulose; Powders; Pressure; Solubility; Stearic Acids; Surface Properties; Time Factors; Water

To develop biodegradable packaging that both acts as a moisture barrier and as antimicrobial activity, nisin and stearic acid were incorporated into a hydroxy propyl methyl cellulose (HPMC) based film. Fifteen percent (w/w HPMC) of stearic acid improved film moisture barrier. However, film mechanical resistance and film antimicrobial activity on Listeria monocytogenes and Staphylococcus aureus pathogenic strains were both reduced. This lower film inhibitory activity was due to interactions between nisin and stearic acid. The molecular interaction was modeled, and an equation was developed to calculate the nisin concentration needed to be incorporated into the film matrix to obtain a desired residual antimicrobial activity. Because the molecular interactions were pH dependent, the impact of the pH of the film-forming solution on film inhibitory activity was investigated. Adjusting the pH to 3 totally avoided stearic acid and nisin interaction, inducing a high film inhibitory activity.

Topics: Anti-Bacterial Agents; Cellulose; Drug Interactions; Fatty Acids; Food Packaging; Hydrogen-Ion Concentration; Hypromellose Derivatives; Listeria monocytogenes; Methylcellulose; Nisin; Staphylococcus aureus; Stearic Acids

Effect of magnesium stearate (MgSt) or calcium stearate (CaSt) on the dissolution profiles of diltiazem hydrochloride in the core of press-coated (PC) tablets with an outer shell composed of hydroxypropylmethylcellulose acetate succinate (HPMCAS) was evaluated by porosity and changes in IR spectra of tablets. In JP first fluid (pH 1.2), the lag time increased with decreasing porosity and was greatest by the addition of MgSt to HPMCAS. While, in JP second fluid (pH 6.8), it increased with decreasing porosity by the addition of CaSt, but hardly changed by the addition of MgSt. Thus, using tablets prepared with the same composition as the outer shell, the changes in IR spectra and uptake amount of the dissolution media after immersion in first fluid and second fluid were determined. The results suggested that some physicochemical interaction occur between MgSt and HPMCAS in tablets with HPMCAS and MgSt and the uptake increased markedly in each dissolution medium. These phenomena seem to cause a prolongation of lag time in first fluid but a shortening of it in second fluid in PC tablets with HPMCAS and MgSt. In contrast, CaSt and HPMCAS did not show such interactions and increased the hydrophobic properties of the outer shell. Consequently, the lag time was only slightly prolonged in first fluid, however, markedly prolonged in second fluid due to suppression of second fluid penetration into micro pores in the outer shell and HPMCAS gel formation on the surface in PC tablets with HPMCAS and CaSt.

Topics: Antihypertensive Agents; Chemistry, Pharmaceutical; Diltiazem; Excipients; Methylcellulose; Porosity; Stearic Acids; Tablets

The objective of this research was to evaluate the effect of hydroxypropylmethylcellulose (HPMC; Methocel K4M Premium) level and type of excipient on theophylline release and to attempt to predict the drug release from hydrophilic swellable matrices. Formulations containing theophylline anhydrous (10% w/w), Methocel K4M Premium (10%, 30%, and 40% w/w), different diluents (Lactose Fast Flo, Avicel PH-101, and Emcompress), and magnesium stearate (0.75% w/w) were prepared by direct compression at a target weight of 450 mg +/- 5% and target hardness of 7 kp to 10 kp. It was found that, as the percentage of polymer in all formulations increased from 10% to 30% or 40%, the drug release decreased. However, there was no significant difference in drug release between formulations containing 30% polymer and formulations containing 40% polymer. At low levels of polymer, the drug release is controlled by the type of diluent used. Avicel PH-101 formulation gave the highest release, while its corresponding Emcompress formulation gave the lowest release. Formulations containing 30% or 40% polymer gave the same release profiles irrespective of the type of diluent used. In all cases, replacement of a portion of Methocel K4M Premium with any diluent resulted in increase of theophylline release. In addition, this investigation demonstrated that the drug release from hydrophilic swellable matrices can be predicted using only a minimum number of experiments.

Topics: Administration, Oral; Excipients; Lactose; Methylcellulose; Models, Theoretical; Oxazines; Polymers; Solubility; Solvents; Stearic Acids; Tablets; Theophylline; Time Factors