• Journal of Pharmaceutical Investigation
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• 제34권6호
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• pp.471-475
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• 2004

Tamsulosin has been frequently used for the treatment of benign prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin matrix tablets and assess their formulation variables. We designed enteric coated sustained-release tamsulosin matrices to fulfill above statement. Aqueous microchannels in the enteric film need to be formed in order to obtain tamsulosin release even in an acidic environment such as gastric region. In the sustained-release tamsulosin matrix, low viscosity hydroxypropylmethylcellulose was used as a rate controller. Povidone K30 was also added to the matrices to facilitate water uptake so that a decrease in the release rate of tamsulosin as time elapses was prevented, possibly leading to pseudo zero-order release of the drug. The matrices were enteric-coated with hydroxypropylmethylcellulose phthalate (HPMCP), along with povidone K30 as an aqueous microchannel former. With the aqueous microchannels formed within the enteric film, tamsulosin could be released in an acidic condition. The release of tamsulosin decreased with increasing thickness of HPMCP membrane while the release rates of tamsulosin from those having different HPMCP thickness in pH 7.2 aqueous media were not considerably different, indicating that the enteric film was promptly dissolved at pH 7.2. These results clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the KFDA.

• Journal of Pharmaceutical Investigation
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• 제33권3호
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• pp.179-185
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• 2003

Melatonin (MT) is an indole amide pineal hormone. It has not only very short half-life but also pH-sensitive property. The sustained release dosage form which delivers MT in a circadian fashion over 8 h is clinical value. The purpose of this study is to prepare sugar beads using multiple coating methods and enteric-coated in a sustained release to evaluate in vitro release characteristics in simulated gastric and intestinal fluids. The $Eudragit^{\circledR}$ as a polymer, sustained release membrane, and triethylcitrate (TEC) as a plasticzer were used. Multi-coated melatonin delivery system was composed of sugar, various excipients, $Eudragit^{\circledR}$ and enteric materials (e.g. hydroxy propyl methyl cellulose phthalate, HPMCP), and prepared by fluid bed coater. The dissolution test was carried out using the basket method at a stirring speed of 100 rpm at $37^{\circ}C$ in simulated gastric (pH 1.2) and intestinal fluid (pH 7.4). The released amount of MT was determined by High performance liquid chromatography method. The morhologies of surface and cross section of multi-coated beads were observed by scanning electron microscope. Size of multi-coated sugar beads was ranged over $1000{\sim}1300\;{\mu}m$. The release rate of MT from coated beads was limited in simulated gastric fluid (pH 1.2), but it was sustained in intestinal fluid (pH 7.4) during $3{\sim}8$ hours. The MT beads may provide small-intestine-targeted device for oral delivery. Studies on animal and relative experiment are in process.

• 약학회지
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• 제41권1호
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• pp.48-59
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• 1997

Sustained release matrix tablets, pellets, and coated pellets for the delivery of sulindac were prepared using cellulose derivatives at various ratios, and evaluated for the dis solution pattern. The release of sulindac, from matrix tablets prepared with low viscosity HPMC was relatively fast, and especially the tablets made of Metolose SM released all of sulindac within 1 hr. The release of drug from tablets made of other HPMC derivatives were retarded in the order of the following: Pharmacoat 645>Pharmacoat 606>Pharrnacoat 606+HPC-L>HPC-L. The most sustained release pattern was observed with the preparation of high viscous polymer. Metolose 90 SH. While release of sulindac, from matrix type pellet containing 10mg/cap of Metolose 90 SH or 60 SH was completed within 1 hr, a prolonged release formulation (30% in 1 hr) was obtained by the inclusion of EC. Pellets coated with HPMC showed a fast release pattern (${\geq}$ 80% within 2 hrs), whereas pellets coated with HPMC and EC (molar ratio 1 : 1) showed a sustained release pattern (${\geq}$ 80% in 12 hrs), vath the release from EC pellets being the most sustained. Fast (naked) and slow release pellets coated with EC, Metolose 60SH 50cps and propylene glycol. and enteric pellets coated with HPMCP 55 and Myvacet$^{\circledR}$ were prepared, and combined at various ratios for the assessment of dissolution pattern. The result indicates the possibility that the development of 24 hr sustained release delivery systems containing sulindac for oral administration could be achieved by means of combining sustained and fast release pellets at a proper portion.

• Journal of Pharmaceutical Investigation
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• 제37권2호
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• pp.119-126
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• 2007

Tablet splitting is used in pharmacy practice to adjust the dose to be administered. However, it also causes several problems such as undesirable effect for sustained release or enteric-coated dosage form, inaccuracy of dose, and pharmacist's safety by splitting hazardous drugs. This study investigated the current status of oral dosage form splitting for patients older than 19 years by analyzing Korea National Health Insurance Claims Database. Out of oral solid drugs prescribed (N=1,486,584) 9.8% of them included tablets (or capsules) split. There were some splitting cases even in sustained release (4.9%), enteric-coated forms (1.3%) and hazardous drugs (2.7%) that were selected by NIOSH (The National Institute for Occupational Safety and Health). The most frequently split drugs were antihistamines, neuropsychotics and steroids. In case of digoxin and warfarin, unit doses in a domestic market were not diverse compared to foreign markets. Guidelines for splitting oral solid dosage forms, approval of diverse doses and conducting dose-response studies for the commonly splitting ingredients on Korean people are needed for the saff and effective use of oral solid drugs.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.39-44
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• 2006

Tamsulosin or a salt thereof such as its hydrochloride salt has been known to have an adrenaline ${\alpha}$ receptor blocking action for urethra and prostate areas. It has been widely used as a drug which lowers the prostate pressure and improves urinary disturbance accompanied by prostate-grand enlargement, thus for the treatment of prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is essentially required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin granules and assess their formulation variables. We designed entric coated sustained-release tamsulosin granules for this purpose. Nano-pores in the outer controlled release membrane were needed in order to obtain initial tamsulosin release even in an acidic environment such as gastric region. In our sustained release osmotic granule system, hydroxypropylmethylcellulose in a drug-containing layer was used as a rate controller. The drug-containing granules were coated with hydroxypropylmethylcellulose phthalate (HPMCP) and Eudragit, along with glycerol triacetate as an aqueous nano-pore former. The release of tamsulosin depended heavily on the type of Eudragit such as RS, RL, NE 30D, used in the formulation of controlled release layer. These results obtained clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the Korean Food and Drug Administration.

• Archives of Pharmacal Research
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• 제28권6호
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• pp.736-742
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• 2005

Xyloglucan (XG), which exhibits thermal sol to gel transition, non-toxicity, and low gelation concentration, is of interest in the development of sustained release carriers for drug delivery. Drug-loaded XG beads were prepared by extruding dropwise a dispersion of indomethacin in aqueous XG solution (2 wt.-$\%$) through a syringe into corn oil. Enteric coating of XG bead was performed using Eudragit L 100 to improve the stability of XG bead in gastrointestinal (GI) track and to achieve gastroresistant drug release. Release behavior of indomethacin from XG beads in vitro was investigated as a function of loading content of drug, pH of release medium, and concentration of coating agent. Adhesive force of XG was also measured using the tensile test. Uniform-sized spherical beads with particle diameters ranging from 692 $\pm$ 30 to 819 $\pm$ 50 $\mu$m were obtained. The effect of drug content on the release of indomethacin from XG beads depended on the medium pH. Release of indomethacin from XG beads was retarded by coating with Eudragit and increased rapidly with the change in medium pH from 1.2 to 7.4. Adhesive force of XG was stronger than that of Carbopol 943 P, a well-known commercial mucoadhesive polymer, in wet state. Results indicate the enteric-coated XG beads may be suitable as a carrier for oral drug delivery of irritant drug in the stomach.