• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.125-142
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• 2011

Solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solid state, is an efficient strategy for improving dissolution of poorly water-soluble drugs for enhancement of their bioavailability. Compared to other conventional formulations such as tablets or capsules, solid dispersion which can be prepared by various methods has many advantages. However, despite numerous studies which have been carried out, limitations for commercializing these products remain to be solved. For example, during the manufacturing process or storage, amorphous form of solid dispersion can be converted into crystalline form. That is, the dissolution rate of solid dispersion would continuously decrease during storage, resulting in a product of no value. To resolve these problems, studies have been conducted on the effects of excipients. In fact, modification of the solid dispersions to overcome these disadvantages has progressed from the first generation to the recent third generation products. In this review, an overview on solid dispersions in general will be given with emphasis on the various manufacturing processes which include the use of polymers and on the stabilization strategies which include methods to prevent crystallization.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.91-97
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• 2003

During the preparation of decoction from the mixture of Coptidis Rhizoma and Scutellariae Radix, insoluble copreciptate was formed. The coprecipitated product (COP) was composed of berberine and baicalin which was the active ingredient of Coptidis Rhizoma and Scutellariae Radix, respectively. COP was slightly soluble in water and could not be well absorbed after oral administration. This poor bioavailibility might be associated with its poor aqueous solubility. With the purpose of increasing the solubility and bioavailibility of COP, hydrolysis of COP by ${\beta}-glucuronidase$ was carried out. Hydrolyzed products (HOP) of COP were identified and assayed for active ingredients. The partition coefficient study, in situ absorption test, and pharmacokinetic study after oral administration were also performed. COP was found to be consisted of berberine and baicalin with molecular ratio of 1 to 1. This compound was hydrolyzed to berberine and baicalin by ${\beta}-glucuronidase$. The rate of hydrolysis was higher at higher temperature up to $50^{\circ}C$ and higher concentration of ${\beta}-glucuronidase$ up to 2500 unit under our experimental conditions. Baicalein, which is more liphophilic than baicalin, showed greater absorption in small intestine than baicalin did. The plasma concentrations of berberine and baicalein after oral administration of HOP were significantly higer than those of COP. The possible mechanism of increased bioavailibility of berberine and baicalein could be the hydrolysis of COP by ${\beta}-glucuronidase$. On the basis of the above results, it might be said that HOP should be a suitable preparation for increasing the bioavailibility of Coptidis Rhizoma and Scutellariae Radix.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.38 no.1
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• pp.1-13
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• 2012

In this review, the use of air bubbles in the pharmaceutical and cosmetic formulations was discussed. The foam bubbles show different characteristics depending on the foaming agents and foam generating devices. The foam bubbles are generated in the form of dispersion of gas bubbles in a solvent. The assessment of stability and rheological properties of bubbles are the starting point for the formulation to be used. Pharmaceutical and cosmetic uses of bubbles are substantially growing, and the foam formulations of drugs can be used for rectal, vaginal, and dermal symptoms. The foam formulation is used in hair mousse, makeup foundation, and sunscreen cosmetics in basic cosmetics. Recently, a lot of studies and patents have been filed in stabilization of active ingredients and delivery of the active ingredient in terms of foam formulations. In the future, foam formulations are expected to be used as novel cosmeceutical formulations.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.176-182
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• 2021

Background: Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. p-coumaric acid (pCA) is an active ingredient of Panax ginseng Meyer (Araliaceae). Methods: Here, we estimated an anti-AD effect of pCA on activated mast cells, activated splenocytes, and a mouse model of AD. Cytokines levels were measured by ELISA and protein activation was analyzed by Western blotting. 2,4-dinitrofluorobenzene (DNFB) was used to induce AD-like skin lesions. Results: The treatment with pCA suppressed the productions and mRNA expressions of thymic stromal lymphopoietin (TSLP), TNF-α, IL-6, and IL-1β in HMC-1 cells. pCA downregulated the expressions of RIP2 and caspase-1, phosphorylated-(p)p38/pJNK/pERK, and pIKKβ/pIkBα/NF-κB in HMC-1 cells. pCA also decreased the productions of TSLP, TNF-α, IL-6, IL-4, and IFN-γ in the supernatant of stimulated splenic cells. Comparing to DNFB-sensitized control group, pCA-treated group alleviated pathological changes of AD-like lesions. pCA decreased the proteins and mRNA expressions levels of TSLP, IL-6, and IL-4 in the skin lesions. Caspase-1 activation was also downregulated by pCA treatment in the AD-like lesions. The serum levels of histamine, IgE, TSLP, TNF-α, IL-6, and IL-4 were suppressed following treatment with pCA. Conclusion: This study suggests that pCA has the potential to improve AD by suppressing TSLP as well as inflammatory cytokines via blocking of caspase-1/NF-κB signal cascade.

• Journal of Pharmaceutical Investigation
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• v.27 no.1
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• pp.65-69
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• 1997

To formulate the topical analgesic preparation of a new capsaicin derivative, DA-5018, a skin penetration evaluation system was established and the effect of composition of formulation on skin penetration using this system was evaluated, The effect of massage on hairless mouse skin penetration and inter-day variation of this effect were investigated using test formulations(cream). In massage group, compared with non-massage group, absolute penetration amount of DA-5018 increased and this experimental system was found to be reproducible, The effects of pH of water phase, ratio of oil/water and the concentration of active ingredient in cream on skin penetration were investigated. The permeation of DA-5018 from the cream increased with increasing pH of water phase to 9. But at pH 10, the permeation of DA-5018 decreased, because of the physical instability of the cream. The permeation of DA-5018 from the cream increased with increasing the ratio of oil/water of the cream. The increase of the content of DA-5018 to 0.3% increased the permeation of DA-5018, but at high concentration(1.0%), the permeation of DA5018 decreased, due to the instability of the cream.

• Journal of Pharmaceutical Investigation
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• v.22 no.2
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• pp.133-137
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• 1992

A novel oral controlled release tablet which may offer more uniform drug level in the body than simple zero-order was developed. The tablet is composed of three layers; outer film layer, middle part compression-coated hydroxypropylmethylcellulose (HPMC) matrix layer, and inner core layer. Each layer contains nicardipine HCl as a model drug. In vitro dissolution test showed that the tablet released the drug in clear three steps; a rapid initial release, followed by a constant rate of release, and then a second phase of fast release of drug. The dissolution characteristics could be modified easily by changing the grade of HPMC, thickness of matrix layer, content of methylcellulose in matrix layer, content of active ingredient in each layer. The pH of dissolution medium did not affect the release profile. This three-step release system is expected to raise the blood concentration rapidly to effective level and to maintain effective blood level longer than simple slow-release systems.

• Toxicological Research
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• v.23 no.2
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• pp.179-187
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• 2007

An International Nonproprietary Name (INN) identifies a pharmaceutical substance or active pharmaceutical ingredient by a unique name that is globally recognized and is of public property. Also known as the generic or common names, the official INNs are provided by national and international nomenclature bodies such as United States Adopted Names (USAN), British Approved Names (BAN), Japanese Accepted Names (JAN) and World Health Organization (WHO). Due to the increasing interest on the development of biotechnological products in Korea, needs for the formulated nomenclature body in Korea are arising for systemic management of newly developed biotechnological products. This study investigated and analyzed nomenclature systems and procedures for the selection of recommended INN for biotechnological products in WHO, USAN and JAN. Based on these documents from advanced countries, we suggested a Korean INN nomenclature organization named KAN (Korean Adopted Names or Korean Agreed Names). Composition and roles of KAN and KAN expert committee and a working process for INN selection/approval were also proposed. Taken together, this study provides a detailed information on INN system recognized worldwide and suggests guidelines for establishment of INN nomenclature system for biotechnological products in Korea.

• Journal of Pharmaceutical Investigation
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• v.29 no.1
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• pp.55-60
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• 1999

We previously showed that a methanol extract of Paeoniae radix decreased total cholesterol level in rats with hyperlipidemia. In order to isolate the active ingredient(s), the methanol extract of Paeoniae radix was fractionated with chloroform/methanol(4:1) solution and isolate into soluble part and insoluble part of the the methanol extract. Above two parts were tested on the experimentally induced hypercholesterolemia in rats for the lowering effect of serum lipoprotein contents. Hyperlipidemia was induced on male Wistar rats by feeding high choleserol diet for 7 days. After oral administration of above samples for 4 weeks, serum lipid profile was verified on these rats by measuring total cholesterol, triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol. The chloroform/methanol(4:1) soluble part and insolule part showed lowering activity of total cholesterol level and triglyceride level at 4 week point significantly(p<0.01 and p<0.05) compare with the control group and the soluble part was more effective.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.91-94
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• 2011

The purpose of this study was to investigate the effect of peptide charge on the interaction between peptide and poly(D,L-lactide-co-glycolide) (PLGA) for evaluating mechanism of acylated peptide formation in PLGA matrix. As a model peptide, octreotide, a synthetic somatostatin analogue and active ingredient of commercial PLGA product, was used. The disulfide group of octreotide was reduced with dithiothreitol and the sulfhydryl groups were modified with N-${\beta}$-maleimidopropionic acid (BMPA) to neutralize octreotide with positive charge in physiological conditions. The BMPA-conjugated octreotide was identified by measuring the molecular mass with liquid chromatography-mass spectrometry. In the interaction study with PLGA, native octreotide showed initial adsorption to PLGA and substantial production of acylated peptides (56% of overall peptide), whereas BMPA-conjugated octreotide showed minimal adsorption to PLGA and no acylation products for 42 days. Consequently, the neutralization of octreotide completely inhibited the peptide acylation by preventing interaction of peptide with PLGA. In conclusion, this study demonstrates that the initial polymer interaction of peptide is important step for peptide acylation in PLGA matrix and suggests the modulation of peptide charge as strategy for inhibiting the formation of acylated peptide impurities.

• Journal of Pharmaceutical Investigation
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• v.40 no.5
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• pp.285-289
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• 2010

Manufacturing a multi-layered tablet such as Xatral XL$^{(R)}$ is more complex and expensive than monolayered tablets, but mono-layered tablets may have less favorable release properties depending on the pharmacodynamics and pharmacokinetics of the active ingredient. We therefore sought to develop a monolayer tablet with a similar dissolution profile to the commercial alfuzosin sustained-release triple layered tablet (Xatral XL$^{(R)}$). We prepared four different mono-layered alfuzosin tablets with different concentrations of hydroxypropyl methycellulose and PVP K-90. Fomulation III with alfuzosion/mg-stearate/ HPMC/ PVP K-90 (10/5/110/95 mg/tab) has a similar dissolution rate to Xatral XL$^{(R)}$, with a similarity factor score of 81.4. However, the swelling and erosion rates of the two formulations were different, and NIR analysis showed differences in the mechanisms of drug release. Thus, although formulation III and Xatral XL$^{(R)}$ show similar dissolution rates, the mechanisms of drug release are different.