• Journal of Pharmaceutical Investigation
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• 제34권5호
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• pp.407-411
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• 2004

New formulations of amlodipine maleate tablet have been investigated to enhance the stability of the drug against light and humidity. Three kinds of amlodipine maleate tablets were prepared. One is prepared by previously known formulation (formulation C), the others were by new formulations using hydrophilic polymer $(Opadry^{\circledR})$ coated granules (formulations A and B). Amlodipine maleate powder was coated with $Opadry^{\circledR}$ to produce the coated granules and it was mixed with other excipients to produce the tabletting mass of new formulations A and B. Dissolution rate of newly formulated tablets was over 80% within 10 minutes in 0.01 M HCl medium, and its dissolution pattern was similar to that of $Norvasc^{\circledR}$ tablet. After 6 months storage under accelerated conditions, residual drug contents of tested formulations (A and B) were not significantly different from formulation C, ranging from 96.2 to 100.4%. Meanwhile, dissolution amount of formulation C was significantly reduced compared to that of formulation A (p<0.05), showing formulation A was more stable than unprotected formulation C at the accelerated conditions. Results of appearance, hardness and disintegration remained unchanged during stability study. In conclusion, it showed that the new formulations had enhanced the stability characteristics and hydrophilic coating technique was an alternative and promising method to improve the stability of amlodipine maleate tablet.

• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.121-127
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• 2003

The objective of this study was to solidify the simvastatin self-microemulsifying drug delivery system (SMEDDS) and to improve the encapsulation efficiency of solidified alginate beads using sodium alginate. Typical simvastatin SMEDDS was composed of various oils, surfactants and cosurfactants. Also solidified-alginate beads was prepared by crosslinking liquid emulsion mixtures containing sodium alginate and other excipients (cetylpyridinum chloride (CP-Cl), hydroxypropyl methylcellulose, starch and so on). in $CaCl_2$ solution, it has been investigated that the drug release pattern and encapsulation efficiency were varied with the ratio of cationic lipid (CP-Cl). Solidified sodium alginate beads containing simvastatin SMEDDS were redispersed into media without re-aggregation. Oil droplet size of redispersed solidified-beads in media produced smaller than the initial size. The density of beads and drug loading amount were increased with increasing cationic lipid content. These systems have advantages of storage stability and predictability of drug release rate.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.83-90
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• 2011

Main objectives of this study were to investigate the effects of a lubricant, magnesium stearate, as blended in a hydrophilic matrix tablet and to identify significant factors using a tablet ejection force and a swelling property. The characteristics of tablet ejection were evaluated with three different compression forces (30, 40, and 60 MPa) and two controlled factors, amount of magnesium stearate and its mixing time. A hydrophilic model drug (terazosin HCl dihydrate) was regarded as a default factor. Tablet swelling was also evaluated. The optimal amount of PEG compared to PEO was set to be 88.50% w/w. As the amount of magnesium stearate was varied from 0.79% to 2.20% w/w, the amount of PEO and PEG was adjusted to meet the tablet's total weight while maintaining the ratio between the two excipients constant. As the mixing time of magnesium stearate was increased, the tablet ejection force and the swelling property were decreased. As the amount of magnesium stearate was increased, the tablet ejection force and the swelling property were decreased since the increased mixing time and the amount of magnesium stearate induced hydrophobic properties of the matrix tablet more effectively. The ejection force of the tablet increased as a result of increase in the compression force, which means that the breaking of tablet/die-wall adhesion energy was also increased when the compression energy was increased. The results gavea valuable guide how to choose suitable amount of the lubricant with processing conditions for the development of hydrophilic matrix formulations.

• Journal of Pharmaceutical Investigation
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• 제40권1호
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• pp.9-14
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• 2010

Lacidipine used for the treatment of hypertension has low water solubility and is classified as BCS Class II category. Gelucire-based solid dispersions (SD) containing lacidipine were prepared by solvent evaporation method to enhance drug dissolution. The powdered forms of SD showed irregularly spherical shape. Thermal behaviors of SD from differential scanning calorimetry indicated that distinct endothermic peak of lacidipine ($184^{\circ}C$) was shifted to lower region ($150.1^{\circ}C$). Drug was present in a crystalline form. NMR spectra also showed some molecular interaction between drug and Gelucire. There was no significant difference in DSC and NMR behaviors between Gelucire 44/14 and Gelucire 50/13. The initial dissolution rate of SD-loaded tablet linearly increased both in water and in water containing 1% tween 20, and much higher than the commercial tablet, $Vaxar^{(R)}$. When the amount of SD was increased, the release rate was greater. The Gelucire 50/13 showed higher dissolution than the Gelucire 44/14. The produced solid dispersion with various kinds of excipients and making tablets, it was found that solid dispersions can increase the solubility in artificial gastric juice and finally increases dissolution rate.

• 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.

• 대한한의학방제학회지
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• 제13권1호
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• pp.1-7
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• 2005

Objective : Okchun-San(OCS) is known as an effective herbal medicine on Type 2 diabetes. We performed to change OCS formulation for freeze drying capsulation. Methods The mixtures of OCS were extracted with water. finally, the filtered solution were evaporated and lyophilized to dry granules. The various ratio of excipients were studied to determine the formation for capsulizing. The samples were inspected for any difference in color, taste and appearance. Results: The prepared form of OCS were dried and weighted 260kg. The lyophilized dry powder yielding 40kg. The suitable ratio of OCS-dry powder and excipient was 10:1. The average weights of On and placebo capsules were $440{\pm}5.28mg$, $465{\pm}7.95mg$, respectively. There was no notable change in color and appearance for both capsuled samples throughout the study period. Conclusions: Therefore in can be concluded that freeze drying capsulation is appropriate form of OCS.

• Journal of Pharmaceutical Investigation
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• 제40권4호
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• pp.255-261
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• 2010

Pluronic as pharmaceutical excipients are listed in the US and British Pharmacopoeia. In particular, Pluronics exist as different compositions and display abundant phases as self-assembling into polymeric micelles with various morphologies depending on the aqueous solvent quality, the composition of structure, and hydrophilic-lipophilic balance (HLB). Pluronics were also known as a P-gp modulator, which was exploited as a reversal molecule of multi-drug resistant (MDR) cancers. We selected a lamella forming Pluronic L92 which has high hydrophobicity and relatively long PEO block among L series of Pluronics. The dispersion of L92 showed great size particles and low stability. To increase the stability and to decrease the particle size, secondary Pluronics (F68, F88, F98, F127, P85, P105, and P123) with relatively long PEO chain were added into 0.1 wt% Pluronic L92 dispersion. The stability of binary systems was increased due to incorporated long PEO chain. Their particle sizes slightly decreased to over 200~400 nm and their solubilization capacity of binary systems didn't change except Pluronic L92/P123 mixtures. The L92/P123 systems showed ca. 100 nm sizes and lowest turbidity among the all systems. The solubilization capacity of 0.1 wt% L92/0.1 wt% P123 was slightly increased compared to 0.1 wt% L92 mono system and other binary systems. These nano-sized binary systems may have potential as alternative drug delivery systems with simple preparation method and overcome the drawbacks of mono systems such as low stability and loading capacity.

• Journal of Pharmaceutical Investigation
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• 제38권1호
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• pp.1-8
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• 2008

Planetary ball mill was used to decrease and control the particle size of excipients. The effects of the weight of sample and the revolution number of mill, and grinding time on the particle size of the ground sample were analyzed by response surface methodology. The optimum conditions for the milling of microcrystalline cellulose were 38.82 g of the weight of sample and 259 rpm of the revolution number of mill, and 45 minutes of grinding time. The predicted value of the particle size at the these conditions was $19.02{\mu}m$, of which the experimental value at the similar conditions was $18.68{\mu}m$. The tensile strength of tablets of single-component powders, such as microcrystalline cellulose, hydroxypropylmethyl cellulose and starch, binary mixtures and ground binary mixtures of these powder were measured at various relative densities. It was found that the logarithm of the tensile strength of the tablets was proportional to the relative density. A simple model, based upon Ryshkewitch-Duckworth equation that was originally proposed for porous materials, has been developed in order to predict the relationship between the tensile strength and relative density of ground binary tablets based on the properties of the constituent single-component powders. The validity of the model has been verified with experimental results for ground binary mixtures. It has demonstrated that this model can well predict the tensile strength of ground binary mixtures based upon the properties of single-component powders, such as true density, and the compositions. When the tensile strength of the mixture of microcrystalline cellulose hydroxypropylmethyl cellulose (90:10) and the ground mixture of them were compared, the tensile strength of the ground mixture decreased widely from 45.3 to 5.6% compared to the mixture in case the relative density of tablets was in the range of $0.7{\sim}0.9$. When the tensile strength of the mixture of microcrystalline cellulose starch (80:20) and the ground mixture of them were compared, the tensile strength of the ground mixture decreased widely from 31.0 to 11.6% compared to the mixture in case the relative density of tablets was in the range of $0.7{\sim}0.9$.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.137-137
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• 1998

Stability, efficacy, absorption and toxicity of a new nasal spray formulation including salmon calcitonin were studied in the laboratory animals. After the effects of many excipients on the stability of salmon calcitonin were evaluated using HPLC system, we selected taurine. Our experimental composition of salmon calcitonin contains taurine as a stabilizer and HPMC (hydroxypropylmethyl cellulose) as an adhesive polymer. After intranasal administration of salmon calcitonin formulations, Mia$\^$(R)/, Men$\^$(R)/ and experimental composition, 22 IU to rats, the reduction percentages of calcium concentration in plasma (ΔD%) were 16.3%, 12.9% and 20.8%, respectively. After intranasal administration of Mia$\^$(R)/, Men$\^$(R)/ and experimental composition to rats, C$\sub$MAX/ (205${\pm}$161, 244${\pm}$117, and 330${\pm}$202 pg/$m\ell$, respectively) and AUC (41585${\pm}$22070, 41191${\pm}$19125, and 63357${\pm}$43126 pg. min/$m\ell$, respectively) were calculated. The permeation coefficients 10$\^$-7/,cm/sec) of salmon calcitonin in Mia$\^$(R)/, Men$\^$(R)/ and experimental composition using Ussing chamber with rabbit nasal mucosa were 4.7${\pm}$1.5, 0.75${\pm}$0.4 and 5.3${\pm}$1.1, respectively. The experimental composition with taurine and HPMC was proved to be excellent because it improved the stability of salmon calcitonin and inhanced the absorption of salmon calcitonin and was not irritative to the nasal mucosa.

• 약학회지
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• 제53권3호
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• pp.101-106
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• 2009

Recombinant interferon alpha-2a is an active formula for the treatment of various cancer cells like malignant melanoma and a variety of virus infection diseases like acute or chronic hepatitis. The bioassay system based on the measurement of virus inhibitory activity by interferon has been used for interferon analysis with low repeatability. Here, we developed the HPLC assay to measure reproducibly interferon alpha-2a protein content which is replaceable to the reported bioassay. This method separated interferon alpha-2a from its oxidized forms and human serum albumin used as excipients. The regression coefficient using interferon alpha-2a EP CRS is more than 0.9 in the range from 5 ${\mu}g/ml$ to 200 ${\mu}g/ml$. The recovery result in the range from 15 ${\mu}g/ml$ to 60 ${\mu}g/ml$ is $97{\sim}104%$ and the precision is $0.2{\sim}1.7%$. The interferon alpha contents of 5 products are about 30 ${\mu}g/ml$.