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For controlled release, latex or pseudolatex coatings to function as designed, it must be cured at temperatures at or slightly above the polymer's glass transition temperature. The focus of this study is to develop an understanding of the curing process and to develop near infrared spectroscopy as a tool for monitoring curing. Differential scanning calorimetry studies were used to determine how the thermal properties of glyceryl monostearate (GMS) and its polymorphic forms relate to the extent of Eudragit® polymer coat curing at different curing temperatures. The different GMS melting endotherms were used to monitor the extent of curing and as references for model development. The calculated melting peak areas for the GMS were plotted versus time and found to be dependent on time and temperature used for curing. Principal component analysis and parallel factor analysis were used to investigate the effect of curing on the films and showed that spectral changes could be could be directly related to the changes associated with the GMS during curing. Partial least square models developed could predict the extent of curing and the final state of GMS post curing. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the feasibility of near-infrared (NIR) spectroscopy for the determination of the influence of sintering temperature and plasticizer levels on the breaking force of extended-release matrix tablets prepared via roller-compaction. Six formulations using theophylline as a model drug, Eudragit® RL PO or Eudragit® RS PO as a matrix former and three levels of TEC (triethyl citrate) as a plasticizer were prepared. The powder blend was roller compacted using a fixed roll-gap of 1.5 mm, feed screw speed to roller speed ratio of 5:1 and roll pressure of 4 MPa. The granules, after removing fines, were compacted into tablets on a Stokes B2 rotary tablet press at a compression force of 7 kN. The tablets were thermally treated at different temperatures (Room Temperature, 50, 75 and 100 °C) for 5 h. These tablets were scanned in reflectance mode in the wavelength range of 400-2500 nm and were evaluated for breaking force. Tablet breaking force significantly increased with increasing plasticizer levels and with increases in the sintering temperature. An increase in tablet hardness produced an upward shift (increase in absorbance) in the NIR spectra. The principle component analysis (PCA) of the spectra was able to distinguish samples with different plasticizer levels and sintering temperatures. In addition, a 9-factor partial least squares (PLS) regression model for tablets containing Eudragit® RL PO had an r2 of 0.9797, a standard error of calibration of 0.6255 and a standard error of cross validation (SECV) of 0.7594. Similar analysis of tablets containing Eudragit® RS PO showed an r2 of 0.9831, a standard error of calibration of 0.9711 and an SECV of 1.192. [ABSTRACT FROM AUTHOR]

The focus of the study was to explore the physical–mechanical properties of curing films and use these properties as a reference for models that relate NIR spectra to the extent of curing. Cast films were cured at 40, 50, and 60°C from 1 to 48h before being scanned on an NIR Spectrometer and analyzed for physical–mechanical properties using an Instron® material testing system. The studies show clear dependence of the physical–mechanical properties on the time and temperature used for curing. Principal component analysis (PCA) and parallel factor analysis (PARAFAC) were performed to investigate the effect of curing on the films. Both PCA and PARAFAC analysis of the NIR spectra showed that spectral features could be directly related to the changes associated with the triethyl citrate (TEC), which directly affected the physical–mechanical properties during curing. Partial least squares (PLS) models were developed that related NIR spectra to the physical–mechanical properties. The use of the Young's Modulus as a reference for NIRS model development resulted in good prediction and was determined to be the best reference for model development. This study demonstrated the NIRS could predict the Young's Modulus which may be used to indicate the extent of curing. [ABSTRACT FROM AUTHOR]

Background: Grewia gum has received attention as a polymeric pharmaceutical excipient in the recent times, being employed as a suspending, film coating, mucoadhesive, and binding agent. The low aqueous solubility, however, has limited its characterization and application. Objective: The purpose of this study was to fractionate and evaluate some physicochemical properties of the gum. Materials and Methods: Aqueous dispersion of the gum was treated at 80°C for 30 min in the presence of sodium chloride and was subsequently fractionated by successively centrifuging it at 3445 rpm for 30 min. Skeletal density, solubility, particle size, and rheological as well as thermal characteristics of the fractions were evaluated. The 1H nuclear magnetic resonance (NMR) and near infrared (NIR) profiles of the fractions were also investigated. The solubility of the gum increased up to fourfold while the viscosity decreased from 244 to as low as70 cP at 40 rpm with some fractions. Results: Grewia gum and the fractions showed good thermal stability exhibiting no thermal events, but charred irreversibly at 297°C irrespective of the fraction. The molecular weight averages by weight and by number of the fractions were between 233,100 and 235,000. The 1H nuclear magnetic resonance (NMR) spectra showed broad peaks. The NMR and NIR spectra suggested the presence of -OH and -OCH3 functional groups in this gum. Conclusion: The fractionation improved solubility and facilitated further investigations on its characteristics that may have implication on its processing, application, and optimization as a potential pharmaceutical excipient. [ABSTRACT FROM AUTHOR]

The predictability of multivariate calibration models, calculated with offline near-infrared spectroscopy (NIRS), assessing impact of magnesium stearate (MgSt) fraction, blending time, and compression force on the tablet breaking force (TBF) of SPRESS ® B820 was statistically compared. Tablets of lubricated SPRESS ® B820 were prepared by varying lubrication and compression conditions using 2 4 full factorial design. Tablets were scanned in reflection mode on a benchtop NIRS. A qualitative principal component analysis and quantitative principal component regression (PCR) and partial least square (PLS) regression relationship between lubricant concentration, blending time, compression force, preprocessed NIR spectra, and measured TBF was calculated with calibration data set. The predictability of calibration models was validated with independent data set. Expected qualitative correlations between MgSt blending time and TBF and a nonlinear relationship between MgSt fraction and TBF were observed. Predictability of PLS comprehensive (0.25%-1% w/w MgSt) model was significantly different from individual 0.25%, 0.5%, and 1.0% w/w MgSt PLS models. In addition, PLS calibration models' predictability was different from PCR calibration models. Thus, added lubrication fraction and adopted multivariate methodology should be selected carefully during the calibration and validation stages as it may have a significant impact on the predictability of the developed models. [ABSTRACT FROM AUTHOR]

Abstract: Fluid bed is an important unit operation in pharmaceutical industry for granulation and drying. To improve our understanding of fluid bed granulation, in-line near infrared spectroscopy (NIRS) and novel environmental temperature and RH data logger called a PyroButton® were used in conjunction with partial least square (PLS) and principal component analysis (PCA) to develop multivariate statistical process control charts (MSPC). These control charts were constructed using real-time moisture, temperature and humidity data obtained from batch experiments. To demonstrate their application, statistical control charts such as Scores, Distance to model (DModX), and Hotelling's T2 were used to monitor the batch evolution process during the granulation and subsequent drying phase; moisture levels were predicted using a validated PLS model. Two data loggers were placed one near the bottom of the granulator bowl plenum where air enters the granulator and another inside the granulator in contact with the product in the fluid bed helped to monitor the humidity and temperature levels during the granulation and drying phase. The control charts were used for real time fault analysis, and were tested on normal batches and on three batches which deviated from normal processing conditions. This study demonstrated the use of NIRS and the use of humidity and temperature data loggers in conjunction with multivariate batch modeling as an effective tool in process understanding and fault determining method to effective process control in fluid bed granulation. [Copyright &y& Elsevier]

Abstract: The objective of this study was to predict dissolution behavior of sustained release theophylline matrix tablets using near infrared (NIR) diffuse reflectance spectroscopy and multivariate calibration models. Eudragit NE 30D was used as a granulation binder to prepare theophylline sustained release tablets. A total of 117 tablets from 5 batches containing different proportions of Eudragit NE 30D were scanned using a NIR spectrometer. The release characteristics of the tablets were investigated in the acetate buffer for 4h. The percentage release at 1, 2, 3 and 4h was used to build the PLS calibration models. The Mahalanobis distance in principal component space and the 2nd derivative transformation were used for sample selection prior to building a four 4-factor partial least square (PLS) calibration models for predicting 1, 2, 3 and 4h release rates. For PLS1h, the standard error of calibration (SEC), and standard error of prediction (SEP) were 2.8 and 3.4%. For PLS2h, the SEC and SEP were 2.7 and 3.5%. For PLS3h, the SEC and SEP were 2.6 and 3.5% and for PLS4h, the SEC and SEP were 3.0 and 3.5%, respectively. For the first time, NIR spectroscopy was successfully applied to predict drug release in the matrix tablets by correlating dissolution profile of each batch to its corresponding Eudragit NE 30D variation in tablet composition. [Copyright &y& Elsevier]

To monitor tableting production using near infrared (NIR) spectroscopy, chemometric models were developed to analyze peak compression force, crushing strength and content uniformity. To measure tablet content uniformity, orbifloxacin tablets with drug content ranging from 60 to 90 mg were made and analyzed using ultraviolet (UV) and NIR spectroscopy. To assess the compression force and crushing strength, several batches of tablets were made on a Stokes B2 rotary tablet press and compression force was varied from 360 to 3500 lb. Principal component analysis (PCA) was used to identify tablets with regular and capped tablets breakage patterns. Comparison of statistical parameters showed that partial least squares (PLS) models gave better fit than the multiple linear regression (MLR) models. The best fit PLS models had a standard error of calibration (SEC) and a standard error of prediction (SEP) for content uniformity of 1.13 and 1.36 mg; for compression force of 69.86 and 59.48 lb and for crushing strength 0.55 kP and 0.57 kP, respectively. NIR spectroscopy in combination with multivariate modeling is a rapid and nondestructive technique that could reliably predict content uniformity, compression force and crushing strength for orbifloxacin tablets. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4040–4051, 2008 [ABSTRACT FROM AUTHOR]

This study investigated the potential of near infrared spectroscopy (NIRS) to assess film coat curing for tablets coated with methacrylate copolymers. The ability of NIRS to monitor film coat curing was studied and compared to conventional methods like differential scanning calorimetry (DSC) and hot-stage microscopy (HSOM). This study showed that variation in the curing temperature and duration affected the NIR spectra for all formulations. These results and the DSC and HSOM results showed that the spectral changes are due to polymer curing. In addition, glass beads, theophylline and orbifloxacin tablets were coated using Eudragit RL, RS, and L 30-D with varying ratios. Principal component analysis (PCA) was performed on the NIR spectra to investigate the effect of curing time and temperature on cast films, uncoated tablets, coated tablets and coated glass beads. Score plots showed that curing duration and temperature affected coated glass beads, uncoated and coated tablets significantly. The amount of drug released at 250 min, and the NIR spectra of cured tablets were used to develop and validate a 7-factor partial least square (PLS) regression calibration for theophylline tablets coated with Eudragit RL:RS 30-D (1:4). This study demonstrated the potential of NIRS in film coat curing and release monitoring. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4067–4086, 2008 [ABSTRACT FROM AUTHOR]

Ammonio methacrylate copolymers are commercially available as Eudragit RL/RS; they differ in the degree of quaternary ammonium group substitution, which gives them different permeabilities. These closely related polymers can be combined in various ratios to control release rate; consequently, release rate is controlled by the polymer composition and coating thickness. Therefore, predicting drug release from methacrylate copolymers using near infrared spectroscopy (NIRS) can be technically difficult. Thus, the objective of this study is to use NIRS to develop multivariate calibration models to predict tablet coat thickness and release rate for tablets coated with varying polymer ratios. A series of sustained release orbifloxacin formulations were developed with varying polymer ratios. Partial least squares (PLS) models were developed to predict coat thickness; samples from these formulations were pooled and a combined calibration was generated. To assess dissolution, tablets were coated using Eudragit RL and RS with ratios of 0:5, 1:4, 2:3, 3:2, 4:1, and 5:0. The amount released at set time-points was used to build PLS models. For the first time, NIRS has been successfully used to monitor Eudragit polymer coat thickness and drug release from tablets coated with various RL:RS ratios, which demonstrates the potential of NIRS as tool for coating process. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4052–4066, 2008 [ABSTRACT FROM AUTHOR]