This study was aimed to develop a stable enteric coated diclofenac sodium tablets using Sureteic without a subcoating layer. Diclofenac uncoated tablets were developed and manufactured through the non direct compression process. Sureteric white aqueous coating dispersion was used as enteric coating material. Sureteric is a special mixture of Polyvinyl Acetate Phthalate (Phthalavin (R), PVAP), plasticizers and other ingredients in a suitable optimized dry powder formulation. The obtained enteric coated tablets were subjected to disintegration and no sign of cracking was observed when they placed in a hydrochloric solution at pH 1.2, but they were completely disintegrated within 10 minutes when they putted in buffered solution at pH6.8. Dissolution test was also conducted by placing tablets in 0.1 M HCl for 2 hours and then 1 hour in phosphate buffer at pH 6.8. Less than 0.9% of drug was released in the acidic phase and up to 97% in the basic medium. These results show that Sureteric can be successfully used to produce diclofenac sodium enteric coated tablets in order to prevent its release in the stomach and facilitate immediate release of the drug in the duodenum. These findings suggest that aqueous enteric coating with Sureteric system is an easy and economical approach for preparing stable diclofenac sodium enteric coat without the use of a subcoating layer.

Near-infrared spectroscopy (NIRS) has become a widely used analytical technique in the pharmaceutical industry, serving for example to determine the active substance or water content of tablets. Its great advantage lies in the minimal sample preparation required and speed of measurement. In a study designed to detect the effects of process on tablet dissolution, we describe the application of NIRS to the detection and identification of changes in uncoated and coated tablets in response to pilot-scale changes in process parameters during melt granulation, compression, and coating. Beginning with a qualitative comparison between pharmaceutical batches, we show that NIRS and principal component analysis can separate batches produced with different melt granulation parameters and differentiate between cores compressed with different compaction forces. Complementary infrared imaging can also explain the difference in dissolution properties between samples produced with different melt granulation parameters. NIRS is sensitive to changes in coating formulation, the quality of a coating excipient (hydroxypropyl methylcellulose), and coating time. In a concluding quantitative analysis, we demonstrate the feasibility of NIRS in a manufacturing context for predicting coating time and detecting production cores failing to meet dissolution test specifications.

THE OBJECTIVES OF THIS STUDY WERE:(i). to use blends of gastrointestinal tract (GIT)-insoluble and enteric polymers (ethyl cellulose and Eudragit L) as coating materials for multiparticulate controlled release dosage forms;(ii). to investigate the effects of the polymer blend ratio and coating level on the resulting drug release patterns; and (iii). to explain the observed phenomena based on the physicochemical properties of the systems. Propranolol HCl-loaded pellets were coated in a fluidized bed coater with organic polymer solutions; thin, drug-containing and drug-free, polymeric films were prepared using a casting knife. In vitro drug release, water uptake and dry weight loss studies were performed in 0.1 M HCl and phosphate buffer pH 7.4, respectively. The apparent drug diffusion coefficients within the polymeric systems were determined using different experimental and theoretical techniques (side-by-side diffusion cells, in vitro drug release from thin films; exact and approximate solutions of Fick's second law of diffusion). A broad range of drug release patterns from coated pellets could be achieved by varying the GIT-insoluble:enteric polymer blend ratio. With increasing relative amounts of Eudragit L, the release rates in both media significantly increased. The increase at low pH could be attributed to an increase in water uptake, as observed with thin films. Interestingly, only partial Eudragit L leaching occurred in phosphate buffer pH 7.4 even at high enteric polymer contents, indicating that the GIT-insoluble polymer effectively hindered the dissolution of the entrapped Eudragit L. At high pH, both polymer leaching and polymer swelling contributed to the control of drug release. The determined apparent drug diffusion coefficients take the two effects adequately into account.

PURPOSE. To provide a method to rapidly screen tablets in the development of new coating technology. METHODS. Near-Infrared (NIR) reflectance spectroscopy was used to quantitatively analyze tablets which were composed of a drug active encasing an active drug core. Diffuse reflectance NIR scans of 240 individual tablets over the range of 1100-2500 nm were obtained. High Performance Liquid Chromatography (HPLC) was used as the reference method. RESULTS. Both qualitative, Principal Component Analysis, and quantitative results showed a strong agreement between the NIR and HPLC methods. The NIR analysis was non-invasive and allowed subsequent testing of the tablets. The contents of the drug active contained in a drug coating was determined to +/- 4% of the target value using NIR analysis. Over 400 samples were analyzed in less than a month utilizing this technique which allowed the optimization of a new coating technology. CONCLUSIONS. NIR analysis allowed the evaluation of the efficiency of a new drug film coating manufacturing process more quickly and inexpensively. Because the Near-Infrared method was non-invasive the tablets were available for further analysis unlike the chromatography method.

Pellets coated with a new aqueous polyvinyl acetate dispersion, Kollicoat SR 30 D, could be compressed into tablets without rupture of the coating providing unchanged release profiles. In contrast, the compression of pellets coated with the ethylcellulose dispersion, Aquacoat ECD 30, resulted in rupture of the coating and an increase in drug release. Plasticizer-free Kollicoat SR coatings were too brittle and ruptured during compression. The addition of only 10% w/w triethyl citrate as plasticizer improved the flexibility of the films significantly and allowed compaction of the pellets. The drug release was almost independent of the compression force and the pellet content of the tablets. The inclusion of various tabletting excipients slightly affected the drug release, primarily because of a different disintegration rate of the tablets. The core size of the starting pellets had no influence on the drug release. Pellets coated with the enteric polymer dispersion Kollicoat 30 D MAE 30 DP [poly(methacrylic acid, ethyl acrylate) 1:1] lost their enteric properties after compression because of the brittle properties of this enteric polymer. Coating of pellets with a mixture of Kollicoat MAE 30 DP and Kollicoat EMM 30 D [poly(ethyl acrylate, methyl methacrylate) 2:1] at a ratio of 70/30 and compaction of the pellets resulted in sufficient enteric properties.

PURPOSE The objectives of this work were (i) to study and understand the physicochemical phenomena which are involved in the swelling and drug release from hydrophilic matrix tablets using the "sequential layer" model, and (ii) to predict the effect of the initial radius height and size of the tablets on the resulting drug release profiles. METHODS Tablets were prepared by direct compression, using hydroxypropyl methylcellulose (HPMC) grades with different average molecular weights as matrix-forming polymers. The in vitro release of chlorpheniramine maleate, propranolol HCl, acetaminophen, theophylline and diclofenac sodium was studied in phosphate buffer (pH 7.4) and 0.1 M HCl, respectively. The initial drug loading varied from 1 to 70%, while the radius and height of the tablets varied from 1 to 8 mm. RESULTS The "sequential layer" model considers water and drug diffusion with non-constant diffusivities and moving boundary conditions, non-homogeneous polymer swelling, drug dissolution, and polymer dissolution. We showed that this model was able to predict the resulting drug release kinetics accurately in all cases. CONCLUSIONS The "sequential layer" model can be used to elucidate the swelling and drug release behavior from hydrophilic matrix tablets and to simulate the effect of the device geometry on the drug release patterns. Hence, it can facilitate the development of new pharmaceutical products.

The objective of this study was to analyse the influence of the composition of the core of the pellets on the in vitro drug release profile. The different materials (drugs and fillers) were chosen according to their relative solubility. Pellets were prepared by a standardised process of extrusion/spheronisation. A selected fraction size (1-1.4 mm diameter) of pellets of each preparation was coated with Surelease (an aqueous dispersion of ethyl cellulose) to give 5% weight gain. The dissolution studies were performed and data analysed in terms of the Area under the Curve (AUC) of the % dissolved as function of time and Mean Dissolution Time (MDT). ANOVA was applied in order to identify the influence factors and the relationship of cross effects. Canonical analysis and multiple regression were employed to quantify these relationships. The film coat was found to be the major factor controlling the drug release. The results however, show that both drug and filler solubility influenced the drug release profile. Some of the unusual results could only be explained if consideration was given to the physical characteristics of both powder and pellets. In particular, the specific surface area of calcium phosphate compared with other fillers played an important role on the release profile of the model drug.

This research studied the influence of buffer composition, pH, and ionic strength on the release of diltiazem hydrochloride from a complex of the drug with lambda carrageenan. Two viscosity grades of carrageenan were also compared. A factorial analysis was used to evaluate the influence of individual variables and their interactions. Both the complex solubility, measured as the drug concentration in equilibrium with the solid complex, and the drug release rate from constant surface area were considered. The increase of ionic strength significantly increased complex solubility in all the buffer systems. A significant effect of polymer grade on complex solubility was evidenced only in phosphate buffer with a pH of 6.8, indicating lower solubility of the complex when higher polymer molecular weight was involved. In most cases, drug release rate decreased when high polymer grade was involved in the complex. Ionic strength did not always have a significant effect on drug release rate and was quantitatively less important than for solubility. Ionic strength especially affected the drug release profiles. At higher ionic strength drug release was no longer constant, but decreased with time, probably because of lower polymer solubility.

Starch acetates (SA) have been investigated as novel, multifunctional excipients for the direct compression tableting process. In this study, the film-forming ability of SA (DS 2.8) and the effect of commonly used plasticizers on the physical properties of SA films were evaluated. The results were compared with the properties of ethylcellulose (EC). Free films were prepared by a solvent-cast method. Mechanical studies, water vapor and drug permeability tests, and thermal analysis (DSC) were used to characterize the film-forming ability of SA and efficiency of tested plasticizers. SA films were tougher and stronger than EC films at the same plasticizer concentration. Also, in most cases, the water vapor permeability of SA films was lower than that of EC films. DSC thermograms supported the findings of the tensile test: plasticizers with several small ester groups (e.g., triacetin and triethyl citrate) were the most compatible with SA. Due to the good mechanical properties, low water vapor, and drug permeabilities of the films, SA seems to be a promising film-former for pharmaceutical coatings. The toughness of SA films may result from their dense film structure, which is due to strong interaction forces between adjacent SA molecular chains.

Two reversed-phase high-performance liquid chromatography (RP-HPLC) methods were developed to investigate the degradation of the acid-labile proton-pump-inhibitor omeprazole in organic polymer solutions and aqueous dispersions of enteric coating polymers (Eudragit L-100, S-100, CAP, HP-55, HPMCAS-HF,-LF, and shellac). The overall goal of the study was to determine the influence of the polymer structure on the degradation of omeprazole, i.e., whether the acid structure of the enteric coating polymers caused an instability of the proton pump inhibitor. Moreover, it was investigated whether a difference in omeprazole degradation could be detected between organic polymer solutions and aqueous dispersions. pKa values of the polymers and pH values of the aqueous dispersions were determined to see whether there was a correlation with the extent of degradation of omeprazole induced by enteric polymers. As the polymers containing phthalate moieties are very susceptible to hydrolysis, the influence of free phthalic acid on omeprazole stability was investigated. Finally, the degradation kinetics of omeprazole in organic polymer solutions were determined. Omeprazole degradation is more pronounced in aqueous polymer dispersions than in organic polymer solutions. The influence of organic polymer solutions on the stability of omeprazole depends on the amount of acidic groups in the polymeric structure, whereas the influence of aqueous polymer dispersions depends on the pH value of the dispersion. The amount of free acids present in some polymers as by-products also cause a degradation of the proton pump inhibitor. Among all investigated polymers, shellac showed the least influence on the stability of omeprazole. The decomposition of omeprazole in organic polymer solutions followed first-order kinetics. The decrease of omeprazole peak area in organic polymer solutions was in the order Eudragit L-100> HPMCAS-HF>shellac.

Twenty diclofenac sodium buccoadhesive discs containing Cp974p, polycarbophil, PEO, SCMC-medium viscosity (SCMC-MV), SCMC-ultrahigh viscosity (SCMC-UHV) or their combinations were prepared. These buccoadhesive discs were evaluated for release pattern, swelling capacity, surface pH, mucoadhesion performance, and in vitro permeation of diclofenac sodium through buccal membranes. In vivo testing of mucoadhesion time, strength of adhesion, irritation, bitterness due to drug swallowing and disc disintegration in the buccal cavity were also performed. Drug bioavailability of a selected diclofenac sodium buccoadhesive product was then compared with that of Voltarin 100 SR tablet. The percentage relative bioavailability of diclofenac sodium from the selected buccoadhesive disc 50 mg was found to be 141.31%.