Pharmaceutical Application of Tablet Film Coating.

Tablet film coating is a common but critical process providing various functionalities to tablets, thereby meeting diverse clinical needs and increasing the value of oral solid dosage forms. Tablet film coating is a technology-driven process and the evolution of coated dosage forms relies on advancements in coating technology, equipment, analytical techniques, and coating materials. Although multiple coating techniques are developed for solvent-based or solvent-free coating processes, each method has advantages and disadvantages that may require continuous technical refinement. In the film coating process, intra- and inter-batch coating uniformity of tablets is critical to ensure the quality of the final product, especially for active film coating containing active pharmaceutical ingredients in the coating layer. In addition to experimental evaluation, computational modeling is also actively pursued to predict the influence of operation parameters on the quality of the final product and optimize process variables of tablet film coating. The concerted efforts of experiments and computational modeling can save time and cost in optimizing the tablet coating process. This review provides a brief overview of tablet film coating technology and modeling approaches with a focus on recent advancements in pharmaceutical applications.

Multilayer-Coated Tablet of Clopidogrel and Rosuvastatin: Preparation and In Vitro/In vivo Characterization.

The acid lability of rosuvastatin hinders the preparation of mixed combination formulations of rosuvastatin with acidic drugs such as clopidogrel. Therefore, the purpose of this study was to develop a multilayer-coated tablet that avoids physicochemical interactions between rosuvastatin and clopidogrel. Among the tested hydrophobic materials, glyceryl behenate was most effective at inhibiting the production of lactone, the acid degradation product of rosuvastatin. Therefore, the multilayer-coated tablet included a hydrophobic separation layer consisting of glyceryl behenate between the clopidogrel core tablet and the rosuvastatin coating layer. In order to prevent delayed dissolution by the stable hydrophobic separation layer, crospovidone was added into the clopidogrel core tablet as an effective disintegrant. Copovidone was also added to the coating layer of rosuvastatin, achieving a dissolution profile comparable to that of the reference drug, Crestor®. The resulting multilayer-coated tablet exhibited similar pharmacokinetic profiles to those of reference drugs (Plavix® and Crestor®) in beagle dogs, and there was no statistically significant difference in the maximum plasma concentration (Cmax), the time to reach the maximum plasma concentration (Tmax), or the area under the plasma-concentration time curve (AUC) between the test and reference formulations. The storage stability tests showed that the amounts of acid degradation products and total impurities were comparable to that of the reference drug. In conclusion, the present study successfully developed a stable multilayer-coated tablet containing both clopidogrel and rosuvastatin that may improve the patient compliance in combination therapy for cardiovascular diseases.

Determination of macelignan in rat plasma by high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic method was developed for the determination of macelignan in rat plasma and applied to the pharmacokinetic study of macelignan in rats. Chromatographic separation was achieved on a conventional ODS column with the mobile phase of water: acetonitrile: methanol = 35:32.5:32.5 (v/v/v %). The flow rate of isocratic elution was 1 mL/min and peaks were detected at 240 nm. The limit of detection was 10 ng/mL and the limit of quantitation was 20 ng/mL. The calibration curve was linear over the concentration range of 50-5000 ng/mL. Intra-and inter-day precision for the assay over the concentration range was below 10 % and the accuracy ranged between 96.0-107% for intra-day and 98.8-114% for inter-day, respectively. The method was applied to the single dose pharmacokinetic study of macelignan in rats and the results showed that this HPLC method was adequate to support the in vivo pharmacokinetic study of macelignan.

Inhibition effect of flavonoids on monocarboxylate transporter 1 (MCT1) in Caco-2 cells.

This study aimed to investigate the inhibition effect of flavonoids on monocarboxylate transporter 1 (MCT1) in Caco-2 cells. The cellular uptake of benzoic acid was examined in the presence and the absence of naringin, naringenin, morin, silybin and quercetin in Caco-2 cells. All the tested flavonoids except naringin significantly inhibited (P<0.05) the cellular uptake of [(14)C]-benzoic acid. Particularly, naringenin and silybin exhibited strong inhibition effects with IC50 values of 23.4 and 30.2 microM, respectively. Kinetic analysis indicated that the inhibition mode of naringenin and silybin on MCT1 activity was competitive with a Ki of 15-20 microM. The effect of flavonoids on the gene expression of MCT1 was also examined by using RT-PCR and western blot analysis. Results indicated that the expression level of MCT1 was not affected by the treatment with naringenin or silybin. The cellular accumulation of naringenin in Caco-2 cells was not changed in the presence of benzoic acid or L-lactic acid, implying that naringenin might not be a substrate of MCT1. In conclusion, some flavonoids appeared to be competitive inhibitors of MCT1, suggesting the potential for diet-drug interactions between flavonoids and MCT1 substrates.

Interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3).

The present study aimed to investigate the interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3). Five flavonoids (morin, silybin, naringin, naringenin and quercetin) were selected and their interaction characteristics with hOAT1 and hOAT3 were examined in MDCK cells overexpressing hOAT1 or hOAT3. Among tested flavonoids, morin and silybin exhibited significant inhibition effects on the cellular uptake of [3H]-para-aminohippuric acid ([3H]-PAH) in MDCK-hOAT1 cells with Ki of 0.46 microM and 24 microM, respectively, while all the tested flavonoids appeared to be less interactive with hOAT3 compared to hOAT1. A kinetic study suggested that morin and silybin inhibited hOAT1-mediated cellular uptake of [3H]-PAH in a competitive manner. Furthermore, morin and silybin were translocated by hOAT1 across the cellular membrane. In conclusion, the present study identified some of flavonoids as a new class of hOAT1 inhibitors, suggesting a potential for flavonoid-drug interactions via the modulation of hOAT1 activity.