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For weakly basic drugs, pH-dependent solubility characteristics can translate into low and incomplete release of these drugs from sustained release formulations. The objective of this study was to quantitatively analyze the relationship between microenvironmental pH modulation and release enhancement of a weakly basic drug in the free base form. A prototype matrix system primarily consisting of trimethoprim (pKa 6.6), hydroxypropyl methylcellulose (HPMC), and a polymeric or nonpolymeric pH modulator was used. Incorporation of the methacrylic acid polymer, Eudragit® L100-55 resulted in marginal release enhancement as the pH modulation effected by this polymer was attenuated by the basicity of the drug. Water uptake and scanning electron microscopy (SEM) studies suggested that Eudragit® L100-55 incorporation also resulted in reduced water uptake and matrix permeability. The effect of nonpolymeric pH modulators on release enhancement was also studied. The lowering in microenvironmental pH by malic acid was sufficiently high and persistent to result in pH-independent release. A correlation plot between the experimentally determined microenvironmental pH, effected by the polymeric and nonpolymeric pH modulators, and percent drug release, exhibited good linearity with a correlation coefficient of 0.83; thereby, indicating that drug diffusion across the gel barrier is the predominating mechanism of release. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1459–1468, 2006 [ABSTRACT FROM AUTHOR]

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]

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]