• Journal of Pharmaceutical Investigation
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• 제29권4호
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• pp.349-353
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• 1999

A novel polymeric tablet of tinidazole (TD) was formulated to treat Helicobacter pylori and Giardia lambria more efficiently with reduced hepatotoxicity by controlling the release of TD after oral administration. TD tablets containing various concentrations of either xanthan gum (XG, viscosity enhancer) and/or polycarbophil (PC, mucoadhesive) were prepared by the wet granulation method. In vitro release of TD into pH 2.0 and pH 5.0 buffer solutions was observed at 37°C by using an USP dissolution tester and an UV (313 nm) spectrophotometer. In vivo absorption of TD tablets was investigated in rabbits by measuring the blood concentration of TD after oral administration using a HPLC. Compared to a commercial TD tablet, in vitro release of TD in both pH 2.0 and pH 5.0 buffer solutions significantly decreased as the concentration: of XG or PC in the tablet increased up to 30%. However, when XG and PC was added in combination, TD was completely released in a pH 5.0 buffer solution within 8 hours, whereas the release of TD in pH 2.0 buffer solution significantly decreased. TD in a commercial tablet was rapidly absorbed after oral administration in rabbits. After oral administration of the polymeric tablets that contain both XG and PC, plasma concentration of TD dramatically decreased. Since the oral absorption of TD significantly decreased by the addition of XG and PC in the tablets while TD completely released in a pH 5.0 buffer solution, it was speculated that more TD was retained in the gastrointestinal tract. Thus, it was possible to control the release of TD by changing the content of XG and/or PC in the tablet, thereby manipulating the release rate and the gastrointestinal retention of TD after oral administration in rabbits.

• Journal of Pharmaceutical Investigation
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• 제31권1호
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• pp.19-25
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• 2001

The purpose of this study was to use a ternary polymeric matrix system for high drug loading of a highly soluble drug for controlled release delivery. The controlled drug delivery of diltiazem HCl (solubility > 50% in water at $25^{\circ}C$) with high loading dose (the final loading dose of drug was 34%) from a ternary polymeric matrix (gelatin, pectin, HPMC) was successfully accomplished. This simple monolithic system with 240 mg drug loading provided near zero-order release over a 24 hour-period by which time the system was completely dissolved. The release kinetics of diltiazem HCl tablet with high loading dose from the designed ternary polymeric system was dependent on the ratios of HPMC : pectin binary mixture. The release rate increased as pectin : HPMC ratio were increased. Swelling behavior of the ternary system and the ionic interaction of formulation components with cationic diltiazem molecule appear to control drug diffusion and the release kinetics. Comparable release profiles between commercial product and the designed system were obtained. The binding study between gelatin with diltiazem HCl showed the presence of two binding sites for drug interaction with subsequent controlled diffusion upon swelling. This designed delivery system is easy to manufacture and drug release behavior is highly reproducible and offers advantages over the existing commercial product.

• Journal of Pharmaceutical Investigation
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• 제31권1호
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• pp.13-18
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• 2001

This study was to investigate the relationship between the gel layer thickness and swelling boundary via strength measurements using texture analysis. The novel texture analysis approach was used to examine the dynamics of swelling behavior in a ternary polymeric matrix tablet. The method permitted the characterization of the changes occurring at the peripheral as well as within interior boundary of the swelling during water ingress. The increase in gel strength for pectin, HPMC, and a ternary mixture with gelatin was found to depend on polymer concentration. Therefore, this method is further applicable to characterize the swelling behavior and provide opportunity to differentiate the gel-layer from that of swelling boundary.

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.7-12
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• 2009

A novel polymeric tablet of Tinidazole was formulated to treat Helicobacter pylori and Giardia lambria more efficiently, It was possible to reduce hepatotoxicity by controlling the release of Tinidazole after peroral administration. A gastric retentive formulation made of naturally occurring carbohydrate polymers and containing Tinidazole was tested in vitro for swelling and dissolution characteristics. Tinidazole tablets containing various concentration of either PEO or HPMC were prepared by the wet granulation method. In vitro release of Tinidazole at pH 1.2 and pH 6.8 buffer solutions was observed at $37^{\circ}C$ by using a KP dissolution method and an UV (313 nm) spectrophotometer. Compared to a commercial Tinidazole tablet, in vitro release of Tinidazole at both pH 1.2 and pH 6.8 buffer solutions significantly decreased as the concentration of PEO or HPMC in the tablet increased up. And the gastric retentive formulation hydrated and swelled back to about 50% of its original size in 30 min. Thus, it was possible to control the release of Tinidazole by changing the content of PEO or HPMC in the tablet, thereby manipulating the release rate and the retention of Tinidazole.

• Journal of Pharmaceutical Investigation
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• 제41권4호
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• pp.239-247
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• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.67-73
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• 2011

Ion exchange resins can be one of the good carriers for sustained drug release. However, the sustained release may not be enough only with themselves and hence film coating with rate controlling polymers can be applied to have a further effect on the drug release. Due to the environmental and economic issues of organic solvent for the polymer coating, aqueous polymeric systems were selected to develop dosage forms. Among the many aqueous polymeric dispersions for the film coating, EC (ethylcellulose) based polymers such as Aquacoat$^{(R)}$ ECD and Surelease$^{(R)}$ were evaluated.A fluid-bed coating was applied as a processing method. The drug release rate was quite dependent on the coating level so the release rate could be modified easily by changing different levels of the coating. The drug release rate in the Aquacoat$^{(R)}$ coated resin particles was strongly dependent on curing, which is a thermal treatment to make homogeneous films and circumvent drug release changes during storage. After dissolution test using the compressed tablets in which the coated resin particles are contained, inhomogeneous coating and even pores could be observed showing that the mechanical properties of EC were not resistant to granulation and compaction process. However, when tablets were prepared in different batches, the release profiles were almost identical showing the feasibility of the coated resin particle as incorporated into the tablet formulation.

• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.185-190
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• 2002

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at $37^{\circ}C$ in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.179-189
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• 2000

Clebopride malate(Cm) is a new benzamide drug which has a potent central antidopaminergic activity possessing antiemetic and anxiolytic properties. A purpose of this study was to assess the feasibility of formulating sustained release preparation by dispersing a drug in hydrophilic polymeric matrices and double layered tablets(DLT), using HPMC, carbopol, PEO, PVP/VA and other polymers as a rate controlling barrier. The matrix and DLT showed optimum dissolution pattern up to 8 hours and the contents of polymer were optimized at 30% level in this preparation. After an oral administration in beagle dog, Cm concentration was determined by use of GC-ECD and pharmacokinetic parameters were calculated by Vallner's method. The AUC of DLT showed similar results and the duration of action was increased 55% compared to that of regular release dosage form. The calculated absorption rate effectiveness(ARE) and controlled release effectiveness(CRE) for DLT increased 50% compared to that of matrix, the overall effectiveness(E) of this product appears to be about 70%. in vivo effectiveness test, DLT showed significant differences from control on antiemetic action of Cm. In consequence, it was possible to conclude that double layered tablet might be a good candidate for the sustained release dosage forms.