Tablet Coatings Research Articles

Drug tablet thickness estimations using air-coupled acoustics

A non-contact/non-destructive acoustic technique for predicting the coating layer thickness of a drug tablet is presented. Quality of tablet coatings can play a major role in the effectiveness of drug delivery. Many pharmaceutical tablets consist of a tablet core and a coated outer cover. Variations in the tablet coating can be indicative of various process problems and, therefore, is of a concern for quality assurance. In the current non-contact measurement system, an air-coupled excitation and laser interferometric detection for predicting the coating layer thickness of a drug tablet is introduced. Drug tablets with different coating thicknesses are vibrated via an acoustic field generated by an air-coupled transducer in a frequency range sufficiently high to excite their several vibrational modes. The tablet surface vibrational responses are acquired at a number of measurement points by a laser interferometer in a non-contact manner. An iterative computational procedure, based on the FE method and Newton's method, was developed and demonstrated to extract the coating layer thicknesses of the tablets from a subset of the measured resonance frequencies.

Comparison of Terahertz Pulse Imaging and Near-Infrared Spectroscopy for Rapid, Non-Destructive Analysis of Tablet Coating Thickness and Uniformity

In this study, coating thickness and uniformity of production-scale pharmaceutical tablets were investigated using near-infrared (NIR) and terahertz pulse imaging (TPI) spectroscopy. Two coating formulations were considered; samples for each coating formulation were obtained at 0, 1, 2, 3, 4, and 5% coating weight. NIR spectra were collected, and regressed with respect to batch percent weight gain. While standard errors of calibration (SEC) less than 0.5% were observed for both formulations, the calibrations were not specifically sensitive to coating thickness. An upper limit for NIR coating thickness analysis was estimated to be ~4- 6% weight gain for this system. The NIR calibrations were used as filters to choose subsets of samples for TPI, and as a secondary method for validation of TPI results. The features in TPS time-domain spectra result when an incident THz plane wave meets a refractive index interface, which may be converted to an absolute distance. Therefore, assuming that a discernible difference in refractive index between coating material and core exists, coating thickness can be determined non-destructively. Coating thickness measurements from TPI and NIR spectroscopy were compared to estimate the lower limit for quantitative TPI coating analysis; a lower limit of ~35 mm was obtained for this system. Optical microscopy was employed on a subset of samples to validate absolute thickness values; reasonable correlations between the three methods were obtained. TPI was considered advantageous relative to the other methods, as similar results were obtained without the need for destructive sampling or empirical calibration development.

The Manufacture and Characterization of Casein Films as Novel Tablet Coatings

The use of casein as a novel film-forming agent, capable of functioning as a pharmaceutical tablet coat, was assessed. Diltiazem HCl core tablets were coated with casein using a pan coater and the efficacy of four different plasticizing agents (glycerol, triethyl citrate, dibutyl sebacate and oleic acid) in producing a continuous tablet-coat were evaluated. Interestingly, only those films formed using oleic acid as a plasticizing agent were capable of producing a continuous, acceptable coat. Consequently, the drug dissolution properties of casein/oleic acid film-coated tablets in pH 1.2 and pH 6.8 media were further investigated. Post-coating thermal treatment (60, 80 and 100°C) was shown to have a significant effect on the properties of the casein-oleic acid films. Diltiazem HCl drug release at pH 1.2 was found to decrease with increasing post-coating heat treatment temperature. Additionally, only coated tablets that were subjected to post-coating heat treatment at 100°C showed sustained drug release properties at pH 6.8, which may be attributed to casein cross-linking.

Study of coat quality of tablets coated by an on-line supercell coater

The aim of this study was to investigate the nature of Supercell coating, an on-line tablet coater that employed a unique pattern of airflow. Tablets coated at different spray rates (4, 6, 8, 10, and 12 mL/min) were analyzed to investigate the influence of different wetting conditions on the quality of coats formed. Scanning electron micrographs showed that tablet coats formed at a spray rate of 4 mL/min consisted of spray-dried droplets that did not coalesce. At a spray rate of 6 mL/min, surface roughness was found to be lower than at the other spray rates, and the coat appeared smoothest, whereby droplets seemed fused together. At higher spray rates, the droplets appeared as branching arms and scale-like structures. This was attributed to the spread of spray droplets by the processing air and mass transfer of wet coating materials between tablets. Further tests showed that coats formed at higher spray rates had higher drug yield, drug uniformity, color uniformity, and density. However, the variability in coat thickness was increased due to the mass transfer of coats and dissolution of tablet core surfaces by the coating material. Since coats of different characteristics can be formed in Supercell coating, the choice of wetting conditions would depend on the type of coat required and the coating materials used.

Noncontact Photo-Acoustic Defect Detection in Drug Tablets

Quality assurance monitoring is of great importance in the pharmaceutical industry for the reason that if defects such as coating layer irregularities, internal cracks, and delamination are present in a drug tablet, the desired dose delivery and bioavailability can be compromised. The U.S. Food and Drug Administration (FDA) established the Process Analytical Technology (PAT) initiative, in order to ensure efficient quality monitoring at each stage of the manufacturing process by the integration of analysis systems into the evaluation procedure. Improving consistency and predictability of tablet action by improving quality and uniformity of tablet coatings as well as ensuring core integrity is required. An ideal technique for quality monitoring would be noninvasive, nondestructive, have a short measurement time, intrinsically safe, and relatively inexpensive. In the proposed acoustic system, a pulsed laser is utilized to generate noncontact mechanical excitations and interferometric detection of transient vibrations of the drug tablets is employed for sensing. Two novel methods to excite vibrational modes in drug tablets are developed and employed: (i) a vibration plate excited by a pulsed-laser and (ii) pulsed laser-induced plasma generated shockwave expansion. Damage in coat and/or core of a tablet weakens its mechanical stiffness and, consequently, affects its acoustic response to an external dynamic force field. From the analysis of frequency spectra and the time-frequency spectrograms obtained under both mechanisms, it can be concluded that defective tablets can be effectively differentiated from the defect-free ones and the proposed proof-of-concept techniques have potential to provide a technology platform to be used in the greater PAT effort.

REMOTE IDENTIFICATION OF FOREIGN SUBJECTS

There are occasions when identification of individuals in civil clothes or uniform may be necessary. In such a case, the ability of terahertz radiation to react to different configuration of, for example, plastic objects, such as tablets, etc. may be used to give a warning sign if the approaching subject is foreign, be he or she in uniform (the one that looks like your own) or in civil clothes. The identification gives an advantage of “checking the credentials” without asking for them. This feature may be especially useful when a military detachment is located close to the adversary occupied territory. The idea for such an identification device came from real situations similar to those that have taken place in Iraq, etc. The code for identification is built in the password tablet. The tablet coatings are semi-transparent to the THz radiation and do not scatter it significantly. The THz pulses, incident on the tablet surface, penetrate through the different coating layers. At each interface a portion of the pulse is reflected back to the detector. The amplitude of the reflected radiation is recorded as a function of time. The resulting pattern is compared with the password.

Mathematical Model to Predict Coat Weight Variability in a Pan Coating Process

The variability in drug release from extended-release products is strongly dependant on the tablet coat weight variability. A mechanistic model to predict the coefficient of variation (CV) of the tablet coat weight is proposed. Although the main assumption is complete random mixing, the model also assumes that each tablet spends a fixed amount of time in the coating zone and receives a fixed amount of coating in each coating event. The number of coating events that each tablet undergoes is given by the binomial distribution. The model predicts that the coat weight CV will depend on the projected area of the tablet (a), velocity of the tablet in the spray zone (V), the number of spray guns (Nspray), the length of the spray zone (L), the total number of tablets (N), and the total spray time (t). The CV is estimated to be equal to . The overall R2 of the model for a side vented pan was 86% with a prediction error standard deviation of 1.3%. Two empirical correction factors were identified to explain the offset.

Multidimensional chromatographic techniques for hydrophilic copolymers: II. Analysis of poly(ethylene glycol)-poly(vinyl acetate) graft copolymers

A large variety of hydrophilic copolymers is applied in different fields of chemical industry including bio, pharma and pharmaceutical applications. For example, poly(ethylene glycol)-poly(vinyl alcohol) graft copolymers that are used as tablet coatings are responsible for the controlled release of the active compounds. These copolymers are produced by grafting of vinyl acetate onto polyethylene glycol (PEG) and subsequent hydrolysis of the poly(ethylene glycol)-poly(vinyl acetate) graft copolymers. The poly(ethylene glycol)-poly(vinyl acetate) copolymers are distributed with regard to molar mass and chemical composition. In addition, they frequently contain the homopolymers polyethylene glycol and polyvinyl acetate. The comprehensive analysis of such complex systems requires hyphenated analytical techniques, including two-dimensional liquid chromatography and combined LC and nuclear magnetic resonance spectroscopy. The development and application of these techniques are discussed in the present paper.

Raman spectroscopy of coated pharmaceutical tablets and physical models for multivariate calibration to tablet coating thickness

Raman spectra of a set of coated pharmaceutical tablets were analyzed for the purpose of calibrating the spectra to tablet coating thickness. Acetaminophen tablets were coated with a hydroxypropylmethylcellulose/polyethylene glycol film coating whose thickness was varied from 0 to 6% weight gain. Coatings were also prepared with two concentrations of TiO 2 at several film thicknesses. The resulting spectral data set was analyzed using several different multivariate calibration procedures. The procedures examined in this study included spectral correction followed by target factor analysis, spectral correction with baseline subtraction followed by principal component regression, and first derivative computation followed by principal component regression. The results demonstrate that target factor analysis is a viable method for calibration of Raman spectra to tablet coating thickness. Calibration based on derivative spectra resulted in linear correlation that was equal to that of the results of target factor analysis for coatings without TiO 2. However, target factor analysis was found to be superior to other methods when TiO 2 was present in the tablet coatings. The effect of sample fluorescence on each of these chemometric methods was also examined. It was found that when photobleaching of fluorescent impurities due to exposure to the Raman excitation source was controlled, the tablet coating thickness could be calibrated to the intensity of the fluorescence signal. The results also demonstrate that for the samples examined here, calibration by target factor analysis is insensitive to variation in fluorescent intensity when the tablet coating emission spectrum is included in the matrix of target vectors.

A Comparative Study of Spouted and Spout-Fluid Beds for Tablet Coating

The performance of spouted, spouted with auxiliary air supply, and spout-fluid beds for the coating of tablets was investigated. The gas–solid regimes of the three systems were confirmed by their hydrodynamic characteristic curves, e.g., pressure drop versus air flow rate. The coating study was developed following a central composite design and using flow regime, suspension feed rate and tablet load in the bed as factors. The dependent variables for the composite design of experiments were weight gain and efficiency. Other coat quality indexes, like tablet surface appearance, hardness, moisture content and gastric resistance are also discussed. The analysis of variance of the experimental data revealed that only the suspension feed rate affected the coating efficiencies and weight gain significantly. The coat quality, e.g., tablet moisture content, hardness, friability, and gastric resistance, were found to be unaffected by the factors studied, according to pharmaceutical standards. The results show that the gas–solid regimes do not affect coating performance.

In vitro drug release rates from asymmetric-membrane tablet coatings: Prediction of phase-inversion dynamics

Most of the controlled-release systems developed for drug delivery applications depend on membrane technology. The dense structure of some membranes used in controlled-release systems can excessively prolong the release of drug due to the low permeability of the coating to drug. To increase the drug release rate, asymmetric-membrane tablet coatings were prepared by a phase-inversion technique using cellulose acetate/acetone/water solution. The roles of the composition of the membrane solution and the evaporation condition on the release rate of drug were determined using in vitro dissolution and morphological studies and predicted phase diagrams. Results show that drug release from asymmetric-membrane based tablet coatings is primarily governed by the dynamics of the phase-inversion process with zero-order or near-zero-order release easily achievable. In an attempt to derive an empirical expression for the release rate of drug as a function of composition of the coating solution, a statistical experimental design was used. Good fit of the experimental data by the empirical expression was obtained. In addition, the predictive capability of the model equation was also found to be satisfactory. Analysis of the significance of each term in the expression indicates that the cellulose acetate:acetone ratio has the most significant influence on the release rate of theophylline.

The Role of Synthetic Pharmaceutical Polymer Excipients in Oral Dosage Forms – Poly(ethylene oxide)‐graft‐poly(vinyl alcohol) Copolymers in Tablet Coatings

AbstractA number of tablet coatings are available to provide a controlled release of pharmaceutically active compounds in the stomach or intestine using both instant or sustained released systems. The preferred properties of these tablet coatings are a low solution viscosity (preferable in water) combined with a phase separated morphology, showing good mechanical properties. PEO‐g‐PVAl copolymers have been developed as an instant‐release tablet coating, and were obtained via a conventional radical polymerisation of VAc in the presence of PEO. No free PEO was observed in the PEO‐g‐PVAl copolymers 1f and 1i using 2D LCCC‐SEC and MALDI‐TOF analysis. Next to the requirement of being PEO free, the PEO‐g‐PVAl copolymers show a good combination of film forming properties, a fast dissolution and a low solution viscosity in water. The phase separated morphology, as demonstrated by TEM, DSC, DMTA, and WAXS experiments, should provide the PEO‐g‐PVAl copolymers with relatively constant mechanical properties. A model reaction, using 2‐methoxyethyl‐ether and 1,4,7,10‐tetraoxacyclododecane, has been developed to imitate the grafting reaction of VAc on PEO. Using this model reaction and using the same reaction conditions (temperature, initiator, concentration, VAc:“PEO” ratio, etc.) as applied in the PEO‐g‐PVAl polymerisation procedure, a degree of grafting for PEO of 13±3% was found. Comparing this figure with the results of LCCC‐SEC and MALDI‐TOF measurements, this figure seems a few percent too high, pointing to a slightly increased reactivity of the two model compounds compared to the PEO used.

Raman spectroscopic measurement of tablet-to-tablet coating variability

We report new results suggesting the feasibility of Raman spectrometry as a tool by which to examine the variability of tablet coatings. Our experiments feature a probe that can operate with a revolving laser focus to average content and coating non-uniformity. Raman spectral changes are correlated with tablet exposure times in a pan coater by means of partial least squares (PLS) multivariate analysis. Statistical models are found to be improved by pre-processing schemes that emphasize spectral changes while minimizing the effects of background light scattering and fluorescence. These pre-processing techniques include multiplicative scatter correction (MSC) and standard normal variate (SNV) transformation, used in concert with Savitzky–Golay second derivative smoothing (SGSD). The two approaches give comparable results yielding R 2 values for PLS calibration and cross-calibrated prediction variance regression of 0.999 and 0.997, respectively. Correlation results and model residual values demonstrate that Raman spectroscopy serves sensitively to reflect the coating thickness of the tablets studied.

Use of the Antioxidant BHT in Asymmetric Membrane Tablet Coatings to Stabilize the Core to the Acid Catalyzed Peroxide Oxidation of a Thioether Drug

Use of the Antioxidant BHT in Asymmetric Membrane Tablet Coatings to Stabilize the Core to the Acid Catalyzed Peroxide Oxidation of a Thioether Drug

Nondestructive Analysis of Tablet Coating Thicknesses Using Terahertz Pulsed Imaging

An understanding of the finished structure of complex pharmaceutical coating is becoming desirable, because tablet coatings are now one of the preferred routes to control the release of active pharmaceutical ingredients. There are few nondestructive techniques capable of examining the coatings of compressed tablets; for example laser induced breakdown spectroscopy has been used but this is a destructive method. Terahertz pulsed imaging offers a potential technique to examine coatings quickly and nondestructively. In the study reported herein, it was possible to distinguish between two brands of across‐the‐counter ibuprofen tablets. The terahertz maps obtained were compared with obtained photographs of cut‐through sections; there was good agreement. The technique is fast: a waveform can be obtained in <20 ms allowing the technique to be considered as a candidate for on‐line or at‐line analysis in a process analytical environment. The lateral resolution of the technique is limited by diffraction of the terahertz focus to about 150 μm at 3 THz, whereas the axial resolution is limited by the terahertz pulse duration, which is <200 fs, to about 30 μm.

Use of the Antioxidant BHT in Asymmetric Membrane Tablet Coatings to Stabilize the Core to the Acid Catalyzed Peroxide Oxidation of a Thioether Drug

The application of a controlled-release asymmetric membrane (AM) coating containing cellulose acetate and polyethylene glycol 3350 (PEG3350) to a stable osmotic tablet core resulted in the oxidative degradation of active ingredient located in the core. It was hypothesized that the production of hydroperoxides from PEG3350 in the coating was responsible for the electrophilic oxidation of drug to the sulfoxide degradation product. The type and solubility of carboxylic acid excipient used to formulate the drug release profile of the osmotic tablet significantly influenced the amount of oxidation. By adding the antioxidant butylated hydroxytoluene (BHT) to the coating, oxidation was significantly inhibited in tablets placed on accelerated stability. Of three additives that were used to prevent oxidation [BHT, ferrous sulfate, and ethylenediaminetetraacetic acid (EDTA)], BHT was shown to be the most effective at preventing sulfoxide formation. The BHT was also shown to be more effective in the coating rather than in the core due to its location closer to the source of the oxidizing species, PEG3350, in the coating.

Heat and Mass Exchange During Fluidized-Bed Coating of Tablets

In the process of coating tablets in a fluidized-bed reactor, the coating material (typically an aqueous solution) supplied via a pneumatic injector distributes homogeneously over the surface of tablets owing to their intensive stirring. The shell grows in a cyclic regime, whereby a thin liquid film formed on tablets occurring in the injector torch zone is dried in the intermediate layer and then the cycle is repeated. Thus, the shell deposition and drying processes are combined, This process is usually described in terms of the heat and mass balance equations. However, use of these relations frequently leads to errors in determination of the process parameters, violation of the system stability, and the related decrease in the efficiency of apparatuses. The results of preliminary investigations showed that one of the main factors determining stability of the coating process is the kinetics of heat and mass exchange between tablets in the fluidized bed and a hot heat-transfer agent. The kinetics of the external heat and mass exchange is determined by changes in the density of water vapor and the temperature of the heat-transfer agent at the tablet surface. The density gradient creates a vapor flow directed from the surface to the core of the heat-transfer agent flow, while the temperature gradient provides for the heat supply to the tablet surface. A strict theoretical analysis of the external heat and mass exchange is based on the system of differential equations describing the transfer of momentum, energy, mass, and heat. The mutual influence of these process is taken into account by introducing the corresponding kinetic coefficients [1]. However, an analytical solution of the external heat and mass exchange problem with allowance for the mutual influence of various factors is extremely difficult to obtain because of difficulties encountered in the calculation of these kinetic coefficients [2]. For this reason, the analysis of heat and mass exchange processes requires using experimental data. In the course of coating, a tablet initially exhibits cooling because the liquid is evaporated at the expense of accumulated heat. Then, the evaporation of liquid from the surface proceeds at a constant temperature at the expense of heat supplied with the heat-transfer agent, after which the tablet is heated again. The molecules of water occurring on the tablet surface diffuse both to the stream of heat-transfer agent and, partly, inward the tablet. However, the latter diffusion proceeds at a significantly lower rate and can be ignored in comparison to the former process. Taking into account that the thickness of the liquid film formed in every wetting cycle is relatively small, we can assume that the rate of heat and mass exchange is determined entirely by the outdiffusion. Then, the process under consideration is described by the following equation: mc

Methods of Polymer Film Formation and Testing for Obtaining Optimum Tablet Coatings

Methods of Polymer Film Formation and Testing for Obtaining Optimum Tablet Coatings

Coatings Technology Handbook, Second Edition

Coatings Technology Handbook, Second Edition

Rapid at-line analysis of coating thickness and uniformity on tablets using laser induced breakdown spectroscopy

Because of the functionality of controlled release tablet coatings, it is desirable to have a rapid means of optimizing coating conditions and predicting the performance of a batch at-line, prior to exhaustive lab analysis. In this paper, Laser Induced Breakdown Spectroscopy (LIBS) was utilized for the first time as a rapid means of simultaneously determining the thickness and uniformity of an enteric coating on compressed tablets. In these studies, the core tablets contained a high concentration of calcium, and the coating contained titanium, silicon, and magnesium, all of which are excellent analytical targets for LIBS. The emission spectra of all four elements were simultaneously monitored as a function of the number of laser pulses in the same spatial location, literally drilling through the coating and into the core tablet. The depth penetration of individual laser pulses was calibrated using profilometry, and the thickness of the coating was determined by the incidence of calcium signal and simultaneous decrease in emission from the other probe elements (titanium, silicon and magnesium) as the laser penetrated the coating. Coating thickness measurements were evaluated by sampling coatings ranging from 5 to 21% (100 mg tablet weight basis). Additionally, LIBS spatial resolution capabilities were exploited to evaluate the film coat thickness uniformity across the tablet faces and edges. Furthermore, tablet to tablet uniformity differences were readily assessable. The results indicate that a change in coating application of less than 2 wt.% on a 100 mg tablet can be easily detected. The rapid analysis times for this technique (10 tablets were analyzed in under 15 min) makes it applicable for in-process evaluation of coating thickness, as well as intra- and inter-tablet coating uniformity on compressed tablets.