• Journal of Pharmaceutical Investigation
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• 제40권5호
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• pp.297-304
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• 2010

The present work focuses on preparation of olanzapine, orally dispersing tablets by direct compression method. Effect of super disintegrant crospovidone, disintegration time, drug content on in vitro release has been studied. A factorial design was employed in formulating a prompt dispersible tablet. The selected independent variables crospovidone and fmelt showed significant effect on dependent variables i.e. disintegration time and percent drug dissolved. Disintegration time and percent drug dissolved decreased with increase in the level of crospovidone. The similarity factor $f_2$ was found to be 97.48 for the developed formulation indicating the release was similar to that of the marketed formulation. Pharmacokinetics of olanzapine after single-dose oral administration of orally disintegrating tablet in normal volunteers were evaluated and the results showed that PK parameters (Cmax, Tmax, AUC) of the designed ODT matrix were similar to those of commercial product, Zyprexa Zydis$^{(R)}$ as a reference.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.275-280
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• 2007

A rapidly disintegration famotidine tablet formulation in the oral cavity was developed using microcrystalline cellulose (MCC) and low-substituted hydroxypropyl cellulose (L-HPC), or additionally cropovidone as an internal disintegrant. Effects of disintegrants on the disintegration time in vitro and hardness were evaluated. Average wetting time of the tablets prepared in scale-up manufacturing process was less than 15 sec. Among the formulations tested, the tablet prepared with crospovidone as an internal disintegrant and Emcocel $90M^{(R)}$ as an external disintegrant showed fastest disintegration. These results may suggest that crospovidone and Emcocel $90M^{(R)}$ possessed excellent wetting nature, which result in the rapid disintegration of tablet.

• 생명과학회지
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• 제33권3호
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• pp.268-276
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• 2023

본 연구는 carvedilol과 ivabradine의 이층정 제형 개발에 있어 carvedilol 속방층의 제형조건을 최적화하기 위해 수행되었다. Full-factorial design of experiments를 사용하여 carvedilol 속방층(wet granulation part)의 첨가제(microcrystalline cellulose, citric acid, crospovidone) 및 타정 시 공정변수(main compression)를 확인하였고 각 독립변수에 대한 7가지 종속변수(함량, 함량 균일성, 경도, 마손도, 붕해, 용출(pH 1.2 및 6.8)를 design expert software를 사용하여 평가하였다. Design of experiments (DoE) 실험에서 도출된 Analysis of Variance (ANOVA) 결과를 통해 main compression은 경도, 마손도, 붕해 시간에 유의한 영향을 주었고, microcrystalline cellulose는 마손도, 용출에 주요한 영향을 주었음을 확인하였다. 또한, citric acid는 마손도, crospovidone은 마손도, 용출에 주요한 영향을 주었음을 확인하였다. DoE실험 결과를 종합하여 최종적으로 도출된 설계공간에 따라 microcrystalline cellulose (약 18.0-32.0 mg), citric acid (약 0.5-12.0 mg), main compression (약 615-837 kgf)의 최적의 범위 내에서 초기 위험평가에서 평가된 모든 위험요인이 제거된 carvedilol 속방층의 최적 제조 범위를 확인하였다.

• 한국분말재료학회지
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• 제30권6호
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• pp.493-501
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• 2023

This study aimed to develop a solid self-nanoemulsifying drug delivery system (solid-SNEDDS) to enhance the formulation of ketoconazole (KTZ), a BCS Class II drug with poor solubility. Ketoconazole, which is insoluble above pH 3, requires solubilization for effective delivery. This SNEDDS comprises oil, surfactant, and co-surfactant, which spontaneously emulsify in the gastrointestinal tract environment to form nanoemulsions with droplet sizes less than 100 nm. The optimal SNE-vehicle composition of oleic acid, TPGS, and PEG 400 at a 10:80:10 weight ratio was determined based on the smallest droplet size achieved. This composition was used to prepare liquid SNEDDS containing ketoconazole. The droplet size and polydispersity index (PDI) of the resulting liquid SNEDDS were analyzed. Subsequently, solid-SNEDDS was fabricated using a spray-drying method with solidifying carriers such as silicon dioxide, crospovidone, and magnesium alumetasilicate. The physicochemical properties of the solid-SNEDDS were characterized by scanning electron microscopy and powder X-ray diffraction, and its solubility, droplet size, and PDI were evaluated. In particular, the solid-SNEDDS containing ketoconazole and crospovidone in a 2:1 weight ratio exhibited significantly enhanced solubility, highlighting its potential for improved medication adherence and dissolution rates.

• 약학회지
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• 제36권6호
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• pp.513-517
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• 1992

The effect of solubility and hygroscopicity of some tablet diluents on the disintegration of enzyme tablets was investigated. Tablets were prepared by direct compression method using sodium starch glycolate, crospovidone, croscarmellose sodium and low-substituted hydroxypropyl cellulose as super disintegrants. Lactose, dextrose, sucrose, sorbitol and calcium phosphate dibasic were selected as typical diluents in this study. They were different in solubility (sucrose, sorbitol>dextrose>dextrose>lactose>calcium phosphate dibasic) and hygroscopicity (sorbitol>sucrose>dextrose>caicium phosphate dibasic, lactose). The disintegrants accelerated differently the disintegration of the tablets prepared with different diluents in the decreasing order of calcium phosphate dibasic>lactose>dextrose>sucrose and sorbitol. These results indicate highly soluble and/or hygroscopic diluents decrease the efficiencies of super disintegrants in the enzyme tablets.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.118-118
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• 1997

Solid dispersions were used to increase the dissolution rate of biphenyl dimethyl dicarboxylate (DDB) in water, with the ultimate goal of optimizing its bioavailability when incoporated into pharmaceuticals. Carriers used were Kollidon 30, Kollidon VA 64, 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD), sodium salicylate or sodium benzoate. DDB solid dispersions were prepared at drug to carrier proportions ranging from 1 : 5 to 1 : 20 (w/w) by solvent evaporation method. DDB tablets (7.5 mg) were prepared by compressing the powder mixture composed of solid dispersions, lactose, corn starch, crospovidone and magnesium stearate using a single-punch press. DDB capsules (7.5 mg) were prepared by filing the mixture into empty hard gelatin capsules (size #1). Dissolution studies of DDB from powdered solid dispersions, tablets and capsules were performed in 900 $m\ell$ of water at 100 rpm and 37$^{\circ}C$ by the paddle method. The dissolved amount was assayed by HPLC and expressed as the mean(%)of three determinations.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.414.1-414.1
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• 2002

To improve the compliance of oral administration of drugs in cancer patients, who are unable to swallow tablets, FDT containing ondansetron HCI($Onseran^{TM}$) was developed with a low-cost manufacturing process. $Onseran^{TM}$ was prepared from ondansetron. mannitol, crospovidone. and others with a direct compression method. The disintegration time and dissolution rate of $Onseran^{TM}$ were assessed according to the USP method. The results were compared with those of the reference drug ($Zofran^{TM}$). (omitted)

• Journal of Pharmaceutical Investigation
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• 제39권6호
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• pp.445-449
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• 2009

According to the statistical data, stroke is about 13.9% of leading causes of death. Some herbal medicines including Paeonia lactiflora, Angelica gigas nakai and Prunus persica, etc., had been reported to be effective in preventing stroke and mBHT (Modified BoyangHwanoTang) was an advanced prescription used in Korean clinics. Orally disintegrating tablets (ODT) is useful for patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders. Further, drugs exhibiting satisfactory absorption through the mucosa intended for immediate pharmacological action could be advantageously formulated in ODT. The aim of this study was to develop the most efficient ODT formulation of mBHT. Corresponding herbal medicines comprising mBHT were extracted with water for 3 hr at 95~$100{^{\circ}C}$ and then dried. mBHT extract was obtained with about 30% of yield. Subsequently, some pharmaceutical excipients such as spray-dried lactose, crospovidone, glyceryl behenate and/or cogrinded-treated arabia gum were used to achieve an immediate disintegration of mBHT ODT in oral cavity. The requirements of ODT with mechanical strength sufficient to stand the rigors of handling and capability of disintegrating within a few seconds in contact with saliva are indispensable. mBHT ODT prepared by the wet granulation method showed a disintegration time of below 30 sec.

• KSBB Journal
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• 제32권2호
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• pp.108-116
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• 2017

Omeprazole, a benzimidazole derivative, suppresses gastric acid secretion by inhibiting $H^+/K^+$ ATPase in gastric parietals cells, and by reducing $H^+$ concentration. To improve stability of esomeprazole magnesium dihydrate (ESMD), enteric-coated preperation was composed of core tablet, subcoating and enteric coating layer. We were evaluated in vitro dissolution characteristics between test and reference ESMD preparation and stability. We could prepare enteric-coated formulation of ESMD by controlling disintegrating agent and coating ratio which could rapidly dissolved in neutral or alkali medium. The formulation D5 with crospovidone of 1.25% and coating ratio of 16.25% had a similar dissolution behavior compare to reference preparation. Difference factor ($f_1$) and similarity factor ($f_2$) were 0~15 and 50~100 and there was no significant difference in bioequivalence between formulations. The content and dissolution rate of formulation D5 were $96.54{\pm}0.21$ and $78.56{\pm}0.87%$ without change of color in accelerated condition ($40^{\circ}C$, RH 75%, high density polyethylene (HDPE) container) for 6 months. This study concluded that our enteric coated preparation of ESMD could be an useful method to improve stability of unstable drug without direct contact with coating material.

• Journal of Pharmaceutical Investigation
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• 제29권3호
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• pp.227-234
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• 1999

Solid dispersions were prepared to increase the dissolution rate of biphenyl dimethyl dicarboxylate (DDB) using water-soluble carriers such as povidone, copolyvidone, $2-hydroxypropyl-{\beta}-cyclodextrin (HPCD)$, sodium salicylate or sodium benzoate by solvent evaporation method. Solid dispersions were characterized by infrared spectrometry, differential scanning calorimetry (DSC) and powder X-ray diffractometry, dissolution and permeation studies. DDB tablets (7.5 mg) were prepared by compressing the powder mixtures composed of solid dispersions, lactose, com starch, crospovidone and magnesium stearate using a single-punch press. DDB capsules (7.5 mg) were also prepared by filling the mixtures in empty hard gelatin capsules (size No.1). From the DSC and powder x-ray diffractometric studies, it was found that DDB was amorphous in the HPCD or copolyvidone solid dispersions. Dissolution rates after 10 min of DDB alone and solid dispersions (1 : 10) in sodium benzoate, sodium salicylate and copolyvidone were 11.8, 23.5, 22.8 and 82.5%, respectively. Dissolution rates of DDB after 30 min from 1 : 10 and 1 : 20 copolyvidone solid dispersions were 80.5 and 95.0%, respectively. For the DDB tablets prepared using solid dispersions (1 : 20), the initial dissolution rate was dependent on carrier material, and was ranked in order, $Kollidon\;30\;{\ll}$ copolyvidone < HPCD. For the HPCD solid dispersion tablets, dissolution rate reached 97.4% after 15 min, but thereafter slowly decreased to 80.7% after 2 hr due to the precipitation of DDB. However, in the case of copolyvidone solid dispersion tablets, dissolution increased linearly and reached 93.4% after 2 hr. Reducing the volume of test medium from 900 to 300 ml markedly decreased the dissolution rate of the tablets containing 1 : 20 HPCD solid dispersions and 1 : 10 copolyvidone solid dispersion. For 1 : 20 copolyvidone solid dispersion tablets, there was no significant change in dissolution rate up to 1 hr with different volumes of test medium. Preparation of the copolyvidone solid dispersion (1 : 20) in capsules markedly delayed the dissolution (31.2 % after 2hr) due to the limited diffusion within capsules. The permeation rate $(13.4\;g/cm^2\;after\;8\;hr)$ of DDB through rabbit duodenal mucosa from copolyvidone solid dispersion (1 : 10) was markedly enhanced, when compared with drug alone or physical mixtures. From overall findings, DDB formulations containing copolyvidone solid dispersions (1 : 20) could be used to remarkably improve the dissolution rate in dosage form of powders and tablets.