orabase and stearic-acid

Ultrasonic treatment can improve the compatibility between a hydrophobic material and a hydrophilic polymer. The light transmittance, crystalline structure, microstructure, surface morphology, moisture barrier, and mechanical properties of a composite film with or without ultrasonication were investigated. Ultrasound increases the film's light transmittance, resulting in a film that has good transparency. Ultrasonication did not change the crystalline structure of the polymer film, but promoted V-type complex formation. The surface of the film became smooth and homogeneous after the film-form suspension underwent ultrasonic treatment. Compared to the control film, after ultrasonication at 70% amplitude with a duration of 30 min, the average roughness and maximum roughness declined from 212 nm to 17.6 nm and from 768.7 nm to 86.5 nm, respectively. The composite film with ultrasonication exhibited better tensile and moisture barrier properties than the nonsonicated film. However, long-term and strong ultrasonication will destroy the polymer structure to some extent.

Topics: Carboxymethylcellulose Sodium; Kinetics; Permeability; Sonication; Starch; Stearic Acids

Using instrumented roll technology, statistical models relating process parameters such as hydraulic pressure, roll speed and screw speed of Vector TF mini roller compactor to ribbon normal stress and density were developed for placebo blends. Normal stress was found to be directly proportional to hydraulic pressure, roll speed and inversely to screw to roll speed ratio. A power-law relationship between ribbon density and normal stress was observed for placebo blends. Models developed for placebo were found to predict ribbon densities of active blends with good accuracy. Standard optimization of roller compaction process parameters involves the investment of a large amount of time and active ingredient. These models can, therefore, be utilized to predict starting instrument settings required to generate a ribbon of desired solid fraction during early-stage development where material availability & time is limited.

Topics: Carboxymethylcellulose Sodium; Cellulose; Drug Compounding; Lactose; Models, Statistical; Placebos; Powders; Pressure; Silicon Dioxide; Stearic Acids

Direct powder compression is the simplest tablet manufacturing method. However, segregation occurs when the drug content is low. It is difficult to assure drug content uniformity in these cases. In this study, we evaluated microcrystalline cellulose (MCC) as a segregation inhibitor in pharmaceutical powders. We assessed the influence of MCC concentration and mixing time on the physical properties of tablets. The tablet formulation comprised acetaminophen, lactose hydrate, cornstarch, MCC (0%, 10%, or 20%), croscarmellose sodium, and magnesium stearate (Mg-St). All powders except Mg-St were premixed for 5, 15, or 25 min. Mg-St was then added and mixed for 5 min to prepare nine pharmaceutical powders. Flowability index and practical angle of internal friction were measured. Tablets were also prepared, and their weight variation, hardness, friability, disintegration time, and drug content variation were evaluated. MCC slightly decreased pharmaceutical powder flowability. Tablet hardness increased and disintegration time decreased with increasing MCC concentration. MCC mixed for ≥ 15 min also significantly lowered drug content variation. A contour plot was prepared to assess the effect of MCC concentration and mixing time on the physical properties of tablets. It was determined that tablets with 50-80 N hardness, ≤ 3.5 min disintegration time, and ≤ 3% drug content variation can be prepared when MCC concentration is 6.5-8.5% and the mixing time is 19-24 min. Therefore, MCC is effective as a segregation inhibitor, and the addition of MCC to tablet formulation improves drug content uniformity.

Topics: Carboxymethylcellulose Sodium; Cellulose; Drug Compounding; Excipients; Hardness; Pharmaceutical Preparations; Powders; Pressure; Stearic Acids; Tablets

Topics: Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Cyproheptadine; Drug Compounding; Excipients; Fumarates; Lactose; Solubility; Starch; Stearic Acids; Tablets; Technology, Pharmaceutical

To evaluate parameters about wettability, water absorption or swelling of excipients in forms of powders or dosage through various methods systematically and explore its correlation with tablet disintegration.. The water penetration and swelling of powders with different proportions of excipients including microcrystalline cellulose (MCC), mannitol, low-substituted hydroxypropyl cellulose (L-HPC), crospolyvinylpyrrolidone (PVPP), carboxymethyl starch sodium (CMS-Na), croscarmellose sodium (CCMC-Na) and magnesium stearate (MgSt) were determined by Washburn capillary rise. Both contact angle of water on the excipient compacts and surface swelling volume were measured by sessile drop technique. Moreover, the test about water absorption and swelling of compacts was fulfilled by a modified method. Eventually, the disintegration of tablets with or without loratadine was performed according to the method described in USP.. These parameters were successfully identified by the methods above, which proved that excipient wettability or swelling properties varied with the structure of excipients. For example, MgSt could improve the water uptake, while impeded tablet swelling. Furthermore, in the present study it is verified that tablet disintegration was closely related to these parameters, especially wetting rate and initial water absorption rate. The higher wetting rate of water on tablet or initial water absorption rate, the faster swelling it be, resulting in the shorter tablet disintegration time.. The methods utilized in the present study were feasible and effective. The disintegration of tablets did relate to these parameters, especially wetting rate and initial water absorption rate.

Topics: Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Drug Compounding; Excipients; Mannitol; Powders; Starch; Stearic Acids; Tablets; Water; Wettability

Holy basil essential oils (HBEO) can be used in many food applications due to antioxidant and antimicrobial attributes, but they are susceptible to degradation upon storage. Therefore, a protective system is required to extend their shelf life. HBEO was microencapsulated by coacervation using gelatin and the microcapsules were subsequently coated with stearic acid (1%, 2%, and 3%) in carboxymethyl cellulose emulsions. The results showed that HBEO contents decreased with increasing stearic acid concentrations from 76% to 59%. Fourier transform infrared spectroscopy analysis suggested that HBEO was stable during microencapsulation. After 3-month storage, changes in appearance were detected in all samples, especially the uncoated and 3% stearic acid-coated microcapsules. Additionally, the surface HBEO content increased significantly, consistent with a distinct increase in darkness and agglomeration. X-ray diffraction analysis revealed the physical change of microcapsules, attributed to the renaturation of gelatin and recrystallization of stearic acid. The antioxidant activity of both non-encapsulated and encapsulated HBEO after storage decreased significantly, except the microcapsule coated with 1% stearic acid (half maximal inhibitory concentration of 0.35 mg/mL), whereas the antimicrobial activity remained constant. The findings suggest that HBEO microcapsules coated with 1% stearic acid could serve as antioxidant and antimicrobial additives in food industries.

Topics: Aluminum; Capsules; Carboxymethylcellulose Sodium; Drug Compounding; Gelatin; Ocimum sanctum; Oils, Volatile; Plant Oils; Stearic Acids

Tablets which were binary mixtures of pioglitazone hydrochloride (PioHCl) with magnesium stearate (MgSt), croscarmellose sodium (CCS), microcrystalline cellulose, or lactose monohydrate were prepared. Two sets of experiments, using intact tablets, were performed. (i) Tablets containing PioHCl (90% w/w) and MgSt were exposed to 25 or 40 °C and 75% RH in a custom-built temperature/humidity chamber. In situ spatiotemporal mapping of disproportionation was performed by transmission-mode synchrotron X-ray diffractometry (SXRD; Argonne National Laboratories). Tablets were scanned in radial direction starting from the top edge of the tablet and moving, in increments of 300 μm, toward the center. There was evidence of disproportionation after 10 min (at 40 °C). The reaction was initiated on the tablet surface and progressed toward the core. (ii) SXRD of tablets stored for a longer time (up to 15 days) enabled the simultaneous quantification of the reactants and products of disproportionation and provided insight into the reaction progression. The influence of sorbed water and microenvironmental acidity on the disproportionation reaction was investigated. The most pronounced reaction was observed in the presence of MgSt followed by CCS. The transformation was solution-mediated, and the spatial heterogeneity in disproportionation could be explained by the migration of sorbed water. There was a good correlation between microenvironmental acidity (pH

Topics: Carboxymethylcellulose Sodium; Cellulose; Excipients; Humidity; Lactose; Pioglitazone; Stearic Acids; Synchrotrons; Tablets; Temperature; Thiazolidinediones; Water; X-Ray Diffraction

Optimizing powder flow and compaction properties are critical for ensuring a robust tablet manufacturing process. The impact of flow and compaction properties of the active pharmaceutical ingredient (API) becomes progressively significant for higher drug load formulations, and for scaling up manufacturing processes. This study demonstrated that flow properties of a powder blend can be improved through API particle engineering, without critically impacting blend tabletability at elevated drug loadings. In studying a jet milled API (D

Topics: Carboxymethylcellulose Sodium; Cellulose; Microscopy, Electron, Scanning; Particle Size; Powders; Rheology; Silicon Dioxide; Stearic Acids; Tablets; Technology, Pharmaceutical

The impact of filler-lubricant particle size ratio variation (3.4-41.6) on the attributes of an immediate-release tablet was compared with the impacts of the manufacturing method used (direct compression or dry granulation) and drug loading (1%, 5%, and 25%), particle size (D[4,3]: 8-114 μm), and drug type (theophylline or ibuprofen). All batches were successfully manufactured, except for direct compression of 25% drug loading of 8 μm (D[4,3]) drug, which exhibited very poor flow properties. All manufactured tablets possessed adequate quality attributes: tablet weight uniformity <4% RSD, tablet potency: 94%-105%, content uniformity <6% RSD, acceptance value ≤ 15, solid fraction: 0.82-0.86, tensile strength >1 MPa, friability ≤ 0.2% weight loss, and disintegration time < 4 min. The filler-lubricant particle size ratio exhibited the greatest impact on blend and granulation particle size and granulation flow, whereas drug property variation dominated blend flow, ribbon solid fraction, and tablet quality attributes. Although statistically significant effects were observed, the results of this study suggest that the manufacturability and performance of this immediate-release tablet formulation is robust to a broad range of variation in drug properties, both within-grade and extra-grade excipient particle size variations, and the choice of manufacturing method.

Topics: Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Drug Compounding; Excipients; Hardness; Ibuprofen; Lactose; Lubricants; Particle Size; Powders; Pressure; Solubility; Stearic Acids; Tablets; Theophylline

The implementation of a blend monitoring and control method based on a process analytical technology such as near infrared spectroscopy requires the selection and optimization of numerous criteria that will affect the monitoring outputs and expected blend end-point. Using a five component formulation, the present article contrasts the modeling strategies and end-point determination of a traditional quantitative method based on the prediction of the blend parameters employing partial least-squares regression with a qualitative strategy based on principal component analysis and Hotelling's T(2) and residual distance to the model, called Prototype. The possibility to monitor and control blend homogeneity with multivariate curve resolution was also assessed. The implementation of the above methods in the presence of designed experiments (with variation of the amount of active ingredient and excipients) and with normal operating condition samples (nominal concentrations of the active ingredient and excipients) was tested. The impact of criteria used to stop the blends (related to precision and/or accuracy) was assessed. Results demonstrated that while all methods showed similarities in their outputs, some approaches were preferred for decision making. The selectivity of regression based methods was also contrasted with the capacity of qualitative methods to determine the homogeneity of the entire formulation.

Topics: Acetaminophen; Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Excipients; Lactose; Least-Squares Analysis; Models, Theoretical; Principal Component Analysis; Spectroscopy, Near-Infrared; Stearic Acids

The aim of this study was to develop and optimize a segregation-free ethyl cellulose-coated extended release multiparticulate formulation to be compressed into tablets without affecting the drug release. Standard tableting excipients (e.g., microcrystalline cellulose, lactose or sorbitol) were layered onto ethyl cellulose-coated propranolol hydrochloride pellets to form a cushion layer in order to eliminate segregation problems normally resulting from particle size difference between coated pellets and excipient powders and second to protect the integrity of the brittle ethyl cellulose coating during compression. The disintegration behavior of the tablets depended strongly on the composition of the cushion layer. Rapid tablet disintegration was obtained with microcrystalline cellulose and the disintegrant sodium croscarmellose. However, the drug release from these cushion-layered pellets still increased upon compression. Incorporation of a glidant into the cushion layer or between the cushion layer and the ethyl cellulose coating reduced the compression effect on drug release markedly. Glidant-containing formulations showed a delayed deformation and damage of the ethyl cellulose-coated pellet upon mechanical stress. In summary, cushion layer based on microcrystalline cellulose facilitated segregation-free compression of a highly compression-sensitive extended release ethyl cellulose-coated pellets into fast-disintegrating and hard tablets without compromising the release properties of the multiparticulates. Directly compressible cushion-layered pellets protected the pellet coating significantly better from damages during tabletting when compared to the conventional compression of blends of coated pellets and excipient powders.

Topics: Carboxymethylcellulose Sodium; Cellulose; Delayed-Action Preparations; Drug Compounding; Excipients; Hardness; Lactose; Sorbitol; Stearic Acids; Tablets

The application of the Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) method to model and control blend processes of pharmaceutical formulations is assessed. Within the MCR-ALS framework, different data analysis approaches have been tested depending on the objective of the study, i.e., knowing the effect of different factors in the evolution of the blending process (modeling) or detecting the blend end-point and monitoring the concentration of the different species during and at the end of the process (control). Data analysis has been carried out studying multiple blending runs simultaneously taking advantage of the multiset mode of the MCR-ALS method. During the ALS optimization, natural constraints, such as non-negativity (spectral and concentration directions) have been applied for blend modeling. When blending control is the main purpose, a variant of the MCR-ALS algorithm with correlation constraint in the concentration direction has been additionally used. This constraint incorporates an internal calibration procedure, which relates resolved concentration values (in arbitrary units) with the real reference concentration values in the calibration samples (known references) providing values in real concentration scale in the final MCR-ALS results. Two systems consisting of pharmaceutical mixtures of an active principle (acetaminophen) with two or four excipients have been investigated. In the first case, MCR results allowed the description of the evolution of the individual compounds and the assessment of some physical effects in the blending process. In the second case, MCR analysis allowed the detection of the end-point of the process and the assessment of the effects linked to variations in the concentration level of the compounds.

Topics: Acetaminophen; Algorithms; Calibration; Carboxymethylcellulose Sodium; Cellulose; Drug Compounding; Excipients; Humans; Lactose; Least-Squares Analysis; Multivariate Analysis; Reference Values; Spectrophotometry, Infrared; Stearic Acids

Instrumented roll technology on Alexanderwerk WP120 roller compactor was developed and utilized successfully for the measurement of normal stress on ribbon during the process. The effects of process parameters such as roll speed (4-12 rpm), feed screw speed (19-53 rpm), and hydraulic roll pressure (40-70 bar) on normal stress and ribbon density were studied using placebo and active pre-blends. The placebo blend consisted of 1:1 ratio of microcrystalline cellulose PH102 and anhydrous lactose with sodium croscarmellose, colloidal silicon dioxide, and magnesium stearate. The active pre-blends were prepared using various combinations of one active ingredient (3-17%, w/w) and lubricant (0.1-0.9%, w/w) levels with remaining excipients same as placebo. Three force transducers (load cells) were installed linearly along the width of the roll, equidistant from each other with one transducer located in the center. Normal stress values recorded by side sensors and were lower than normal stress values recorded by middle sensor and showed greater variability than middle sensor. Normal stress was found to be directly proportional to hydraulic pressure and inversely to screw to roll speed ratio. For active pre-blends, normal stress was also a function of compressibility. For placebo pre-blends, ribbon density increased as normal stress increased. For active pre-blends, in addition to normal stress, ribbon density was also a function of gap. Models developed using placebo were found to predict ribbon densities of active blends with good accuracy and the prediction error decreased as the drug concentration of active blend decreased. Effective angle of internal friction and compressibility properties of active pre blend may be used as key indicators for predicting ribbon densities of active blend using placebo ribbon density model. Feasibility of on-line prediction of ribbon density during roller compaction was demonstrated using porosity-pressure data of pre-blend and normal stress measurements. Effect of vacuum to de-aerate pre blend prior to entering the nip zone was studied. Varying levels of vacuum for de-aeration of placebo pre blend did not affect the normal stress values. However, turning off vacuum completely caused an increase in normal stress with subsequent decrease in gap. Use of instrumented roll demonstrated potential to reduce the number of DOE runs by enhancing fundamental understanding of relationship between normal stress on ribbon and process parameters.

Topics: Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Colloids; Drug Compounding; Equipment Design; Excipients; Feasibility Studies; Friction; Lactose; Lubricants; Models, Chemical; Pharmaceutical Preparations; Porosity; Pressure; Silicon Dioxide; Stearic Acids; Stress, Mechanical; Technology, Pharmaceutical; Tensile Strength; Transducers, Pressure

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

To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS). The DOE effect analysis was used to evaluate the interactions and effects of three design factors (water amount, wet massing time and lubrication time), on response variables (blend flow, compressibility and tablet dissolution). The design space was established by the combined use of DOE, optimization and multivariate analysis to ensure desired CQAs. Multivariate analysis of all variables from the DOE batches was conducted to study relationships between the variables and to evaluate the impact of material attributes/process parameters on manufacturability and final product CQAs. The integrated multivariate approach exemplifies application of QbD principles and tools to drug product and process development.

Topics: Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Excipients; Models, Chemical; Models, Statistical; Multivariate Analysis; Principal Component Analysis; Quality Control; Solubility; Stearic Acids; Systems Integration; Tablets; Technology, Pharmaceutical; Time Factors; Water

It was attempted to produce novel furosemide (FS) fast-disintegrating tablets by direct compression. The combination of FS, microcrystalline cellulose, croscarmellose sodium and xylitol was used as the basic formulation, and sucrose stearic acid ester (SSE) was chosen as an additional additive. The tablets with SSE were prepared by the simple addition of SSE, using a lyophilized mixture of FS and SSE or using a FS/SSE mixture obtained by evaporation of their ethanol solution. Only the tablets, produced using the FS/SSE mixture obtained by organic solvent (ethanol) evaporation, showed hardness of more than 30 N and a disintegration time of less than 20 s, which were the properties suitable for fast-disintegrating tablets. These properties were considered to result from well-mixed and fine-powdered SSE and FS.

Topics: Antihypertensive Agents; Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Diuretics; Drug Compounding; Esters; Ethanol; Excipients; Flavoring Agents; Furosemide; Microscopy, Electron, Scanning; Solubility; Solvents; Stearic Acids; Sucrose; Tablets; Xylitol

This study has investigated an artificial intelligence technology - model trees - as a modelling tool applied to an immediate release tablet formulation database. The modelling performance was compared with artificial neural networks that have been well established and widely applied in the pharmaceutical product formulation fields. The predictability of generated models was validated on unseen data and judged by correlation coefficient R(2). Output from the model tree analyses produced multivariate linear equations which predicted tablet tensile strength, disintegration time, and drug dissolution profiles of similar quality to neural network models. However, additional and valuable knowledge hidden in the formulation database was extracted from these equations. It is concluded that, as a transparent technology, model trees are useful tools to formulators.

Topics: Artificial Intelligence; Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Decision Trees; Drug Compounding; Excipients; Models, Chemical; Neural Networks, Computer; Pharmaceutical Preparations; Reproducibility of Results; Silica Gel; Silicon Dioxide; Solubility; Stearic Acids; Tablets; Technology, Pharmaceutical; Tensile Strength; Time Factors

Understanding of the cause-effect relationships between formulation ingredients, process conditions and product properties is essential for developing a quality product. However, the formulation knowledge is often hidden in experimental data and not easily interpretable. This study compares neurofuzzy logic and decision tree approaches in discovering hidden knowledge from an immediate release tablet formulation database relating formulation ingredients (silica aerogel, magnesium stearate, microcrystalline cellulose and sodium carboxymethylcellulose) and process variables (dwell time and compression force) to tablet properties (tensile strength, disintegration time, friability, capping and drug dissolution at various time intervals). Both approaches successfully generated useful knowledge in the form of either "if then" rules or decision trees. Although different strategies are employed by the two approaches in generating rules/trees, similar knowledge was discovered in most cases. However, as decision trees are not able to deal with continuous dependent variables, data discretisation procedures are generally required.

Topics: Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Decision Trees; Drug Compounding; Excipients; Fuzzy Logic; Models, Chemical; Pharmaceutical Preparations; Reproducibility of Results; Silica Gel; Silicon Dioxide; Solubility; Stearic Acids; Tablets; Technology, Pharmaceutical; Tensile Strength; Time Factors

Chronopharmaceutical capsules, ethylcellulose-coated to prevent water ingress, exhibited clearly different release characteristics when coated by organic or aqueous processes. Organic-coated capsules produced a delayed pulse release, whereas aqueous-coated capsules exhibited less delayed and more erratic release behaviour. Nuclear magnetic resonance microscopy was used to elucidate the internal mechanisms underlying this behaviour by studying the routes of internal water transport and the timescale and sequence of events leading to the pulse. Images showed that the seal between the shell and the tablet plug is a key route of water penetration in these dosage forms. There is evidence for a more efficient seal in the organic-coated capsule, and although some hydration of the contents was evident, erosion of the tablet plug is most probably the controlling factor in timed release. The premature failure of the aqueous-coated capsule appears to be a result of rapid influx of water between plug and capsule with hydration of the low substituted hydroxypropylcellulose expulsion agent. As a result of this, the tablet plug remains intact, but appears unable to be ejected. The resulting significant pressure build-up causes premature release by distortion and splitting of the capsule shell. These events may be aided by a weakening of the aqueous-coated gelatin shell by hydration from the inside, and at the mouth of the capsule where previous electron microscope studies have shown incomplete coating of the inside by the aqueous process.

Topics: Calcium Phosphates; Capsules; Carboxymethylcellulose Sodium; Cellulose; Delayed-Action Preparations; Drug Delivery Systems; Excipients; Image Processing, Computer-Assisted; Kinetics; Lactose; Magnetic Resonance Imaging; Propranolol; Solvents; Spectrophotometry, Ultraviolet; Stearic Acids; Water

Near-infrared (near-IR) spectroscopy was used to qualitatively assess the homogeneity of a typical direct compression pharmaceutical powder blend consisting of hydrochlorothiazide, fast-flo lactose, croscarmellose sodium, and magnesium stearate. Near-IR diffuse reflectance spectra were collected from thieved powder samples using a grating-based spectrometer. A second-derivative calculation and principal component analysis were performed on the spectra prior to qualitative evaluation. Blend homogeneity was determined using single- and multiple-sample bootstrap algorithms and traditional chi-square analysis. The results suggested that bootstrap techniques provided greater sensitivity for assessing blend homogeneity than chi-square calculations and that near-IR has great potential as an analytical tool in powder blend analysis.

Topics: Carboxymethylcellulose Sodium; Hydrochlorothiazide; Lactose; Powders; Spectroscopy, Near-Infrared; Stearic Acids; Technology, Pharmaceutical; Time Factors

The aim of the present work was to optimize a tablet formulation containing a physical mixture of a practically insoluble drug (prednisone) with a superdisintegrant (croscarmellose sodium) and two filler-binders characterized by differing water solubility (dicalcium phosphate dihydrate and anhydrous beta-lactose). Crushing strength, disintegration, and dissolution were measured for 10 formulations distributed over a factor space according to a simplex lattice design for a special cubic model. Multiple linear regression analysis was used to assess the best fit for each variable. The model predicted that increasing the amount of disintegrant to a critical amount (50%) would result in reduced disintegration time for dicalcium phosphate/beta-lactose ratios > 0.3, no changes in disintegration time for ratios < 0.3, and for all ratios an improvement in dissolution at 10 min. Crushing strength values of dicalcium phosphate increased with increasing disintegration concentration but not for beta-lactose tablets. The physical mixture of a practically insoluble drug with a superdisintegrant was confirmed as a valid approach to the improvement of dissolution, even in presence of other components. The solubility of the filler-binders influenced the minimum amount of disintegrant needed; when a soluble diluent was used, the amount of disintegrant required was reduced.

Topics: Anti-Inflammatory Agents; Calcium Phosphates; Carboxymethylcellulose Sodium; Excipients; Hardness Tests; Kinetics; Lactose; Prednisone; Regression Analysis; Solubility; Stearic Acids; Tablets

Topics: Carboxymethylcellulose Sodium; Peanut Oil; Pediatrics; Penicillin G Procaine; Penicillins; Plant Oils; Sesame Oil; Stearic Acids; Water

Topics: Carboxymethylcellulose Sodium; Penicillin G Procaine; Penicillins; Stearic Acids; Suspensions; Water