• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.207-211
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• 2000

The objective of this work is to investigate the effect of molecular weight of poly(ethylene oxide) (PEO) and release medium on the release of nifedipine (NP) from PEO tablets containing NP and to get some mechanistic insights into the release of NP. The tablets containing NP were prepared by direct compression, using a flat-faced punch and die. The molecular weights of PEOs used were 200K, 900K, 2000K and 7,000K. The release kinetics were studied for 24 hours in aqueous ethanol solution, using a dissolution tester at $36.5^{\circ}C$ and 100 rpm. Drug release rate increased, as the concentration of ethanol in the dissolution medium increased, due to the increased solubility of NP. As the molecular weight of PEO increased, release rate decreased, due to the slower swelling and dissolution of PEO. The power values obtained by fitting data to the power law expression $(M_t/M_{\infty}=kt^n)$ indicated that, at low ethanol concentration, the release of NP is governed by anomalous diffusion. However, as the ethanol concentration increases, diffusional release becomes to prevail over anomalous or zero-order release. Overall, these results provided some insights into the release of NP from PEO tablet.

• 공업화학
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• 제7권4호
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• pp.735-742
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• 1996

장시간에 걸쳐 약물의 흡수가 일어날 수 있는 고분자 matrix을 개발하고자, 글리세린과 증류수를 혼합 교반 시킨 후, 분자량이 서로 다른 세 종류의 dextran을 각각 첨가하여 용해시켰다. 이 용액에 silver sulfadiazine을 분산시켜 matrix를 제조하였다. 이렇게 제조된 고분자 matrix로부터 약물 방출 양상을 규명하기 위해 인산염 완충용액 중에서 약물의 함유량 변화, dextran의 분자량 변화 및 글리세린의 농도 변화에 영향을 미치는 인자들에 관하여 연구 검토한 바 다음과 같은 결론을 얻었다. 고분자 matrix내의 silver sulfadiazine의 함유량이 증가할수록 약물 방출 지속 시간은 11.2일, 14.0일 및 15.8일로 지연되었다. Dextran의 분자량 변화에 대해서는 약 14.0일로 거의 같은 약물 방출 pattern을 보임으로써 겉보기 방출속도상수 (K)값과의 관계와 일치하는 결과를 얻었다. 그러나 글리세린의 함유량이 증가함에 따라 약물 방출 지속 시간은 각각 18.0일, 17.0일, 14.0일, 13.0일 및 10.0일로 감소하였다.

• Journal of Pharmaceutical Investigation
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• 제27권4호
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• pp.313-321
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• 1997

Ion exchange resin complexes of famotidine have been prepared by the reaction of famotidine solution with activated ion exchange resins. Complex formation efficiency between famotidine and ion exchange resin was about $80{\sim}90%$ in average, calculated by HPLC determination. Drug release characteristics from the resin complexes were evaluated by the modified percolation method. Famotidine release was dependent on the type of ion exchange resins. In the case of weakly acidic resin complexes, the cumulative released amount of famotidine was more than 90% for 1hr in pH 1.2 buffer solution. However, in the case of strongly acidic resin complexes, it was less than 5% for 3hr in the same medium. Strongly acidic resins revealed some advantages over weakly, acidic resins for overcoming instability of famotidine in gastric juice. In addition, strongly acidic resin complexes showed controlled release of famotidine in pH 6.8 buffer solution, showing the result of about 60 to 70% of drug release for 5hr. After oral administrations of famotidine-resin complexes to rats as dose of 40 mg equivalent/kg, the pharmacokinetic parameters of famotidine were obtained by model independent analysis and compared with those of famotidine solution or suspension. $C_{max}$ of famotidine-resin complex was lower than that of famotidine solution or suspension. MRT, MAT, and MDT of the complexes were greater than those of famotidine solution or suspension. From these results, it was expected that famotidine was released slowly from the complexes and absorbed continuously into systemic circulation. It was recognized that drug release from the complexes was the rate-limiting step in drug absorption, since there were close correlations between in vitro drug release and in vivo pharmacokinetic parameters.

• Journal of Pharmaceutical Investigation
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• 제24권3호
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• pp.155-165
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• 1994

Some mucoadhesive polymers such as hydroxypropylcelluose (HPC) and carbopol-934 (CP) have been employed for the preparation of mucoadhesive polymeric systems, and their physical properties including mucoadhesion, swelling, and drug release were evaluated. A new simple experimental technique that can quantitatively measure the bioadhesive properties of various polymeric systems has been developed by the methods of detachment force test. As the polymeric systems, the discs of freeze-dried HPC/CP solid dispersions were prepared. The mucosa used in these tests were upper, middle, and lower parts of small intestine of male rats weighing $300{\sim}350\;g$. Detachment forces were increased as the mole fraction of CP increased in discs of HPC/CP solid dispersions. In the points of intestinal site dependence of mucoadhesion, the solid dispersions revealed non-specific mucoadhesion to the intestine. Swelling and drug release characteristics of mucoadhesive polymeric systems were studied extensively to find out the feasibility for the oral controlled delivery systems. Swelling ratio, expressed as the final height/initial height, has been determined in various pH buffer solutions. Hydrochlorothiazide (HCT) was employed as a model drug for release study. Apparent swelling and drug release rate constants, $K_s$ and $K_r$ respectively, were obtained from the square-root time plot of either swelling ratio or released amount of drug, particularly for the time periods before reaching the equilibrium. As a result, the swelling ratio of HPC/CP solid dispersions was increased as the weight percentage of CP increased. Similarly, the release of HCT from the solid dispersions was dependent on pH changes and CP contents, resulted in the slower release of HCT with the increases of pH and CP contents.

• 약학회지
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• 제18권1호
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• pp.49-58
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• 1974

Tablet product design problem was structured as constrained optimization problem and subsequently solved by multiple regression analysis and Lagrangian method of optimization. Aluminum flufenamate was the drug chosen and microcrystalline cellulose nad starch were the binder and disintegrant, respectivley. The effect of the binder and disintegrant concentration on tablet hardness, friability, volume, in vitro release rate, and urinary excretion rate of drug in human subjects was recorded. Since a reasonably rapid release rate of drug is generally an important objective in the design of solid dosage form, optimization of this parameter was employed in studying the applicability of constrained optimization to a pharmaceutical product design problem. In addition to finding optimal sitivity analysis studies to such problems was also illustratd. It would appear that prediction of the in vivo t$_{50%}$ response from a knowledge of the incitro t$_{50%}$ response can be made fairly accurately for the tablet system used in this study.

• KSBB Journal
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• 제6권1호
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• pp.79-83
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• 1991

생물고분자인 PHB로 고분자 matrix를 제조하여 대상약물인 silver sulfadiazine의 방출기전을 연구하였다. 고분자 matrix내의 PHB의 함유량 증가와 matrix의 두께비가 증가할수록 방출속도는 늦어졌다. 그러나 가소제량이 증가함에 따라 방출 기전은 각각 18, 17, 16, 12 및 10시간으로 감소하였다. 이 제형은 약물방출기전은 Higuchi model에 따른 확산으로 생각되었다. 결론적으로 PHB의 함유량과 가소제의 함유량 및 matrix 두께의 상관관계를 조절하므로써 특정한 약물의 방출기전을 얻을 수 있는 maxtrx형태의 개발 가능성을 보였다.

• 폴리머
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• 제36권3호
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• pp.332-337
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• 2012

본 연구는 약물의 용해도에 따른 서방성 용출 거동의 특성을 파악하기 위해 수행되었으며, 이에 따라 고분자의 입도에 따른 염산벤라팍신과 카바마제핀의 정제를 제조하였다. 사용된 고분자는 경구를 통한 서방성 약물전달 시스템 설계에 가장 널리 사용되는 히드록시 프로필 메틸셀룰로오스(HPMC)이며, HPMC의 입도 분포에 따른 팽윤 속도의 차이는 중요한 특성으로 약물의 용출에 큰 영향을 미친다. HPMC 입도에 따른 정제 표면을 분석하기 위해 SEM을 사용하였으며, 결정학적 특성을 파악하기 위해 DSC를 이용하여 분석하였고, 용출 특성의 주요 메카니즘을 파악하기 위해 용출 모델식을 적용하였다. 본 연구를 통해 약물의 용해도 및 HPMC의 입도에 따라 약물의 용출 거동을 조절할 수 있었다.

• Journal of Pharmaceutical Investigation
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• 제36권3호
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• pp.175-184
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• 2006

Poly(D,L-lacic acid)(PLA) microshperes containing loazepam were prepared by a solvent-emulsion evaporation method and their release patterns were investigated in vitro. Various batches of microspheres with different size and drug content were obtained by changing the ratio of lorazepam to PLA, PLA concentration in the dispersed phase and stirring rate. Rod-like lorazepam crystals on microsphere surface, which were released rapidly and could act as a loading dose, were observed with increasing drug content. The release rate was increased with increase in drug contents and decrease in the molecular weight of PLA. The release rate of lorazepam for long-acting injectable delivery system in vitro, which would aid in Predicting in vivo release Profile, could be controlled by properly optimizing various factors affecting characteristics of microspheres.

• Archives of Pharmacal Research
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• 제15권2호
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• pp.162-168
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• 1992

Release characteristics of five different types of hydrophilic albumin microspheres (HAM) containing different ratios of methotrexate-albumin (MTX-HSA) conjugates to free MTX: 1 : 0 (HAMC), 3 :1 (HAMC 3F), 1 :1 (HAMCF), 1:3 (HAMCF3) and 0 : 1 (HAMF) were investigated in the absence or presence of protease using dissolution tester. In all the HAMs studied except HAMC, the MTX was released bi-exponentially in the absence of protease; an initial fast release period up to approximately 6h, and thereafter the release rate was very much slower. The fast release of MTX from the HAMs (such as HAMC3F, HAMCF, HAMCF3 and HAMF) at the initial phase in probably due to the release of "physically associated" MTX from the core of the HAMs. The initial rate constants were 7.2, 8.7, 8.5 and 5.9 times greater than the second rate constants for HAMF, HAMCF3, HAMCF and HAMC3F, respectively. MTX release from HAMC was very slow and mono-phasic. It was at most 2.2% of the total entrapped amount by 24 h. The protease accelerated the release of MTX from the HAMs. The percentages of MTX released from HAMs up to 24 h were 100, 89.0, 75.0, 66.0 and 61.0% for HAMF, HAMCF3, HAMCF, HAMC3F and HAMC, respectively in the presence of protease and the corresponding values in the absence of protease were 30.2 19.0, 10.0, 6.5 and 2.2%, respectively. In vitro release of MTX in the presence of protease varied according to the ratios of MTX-HSA conjugates to MTX; the data set from HAMF, HAMCF3 and HAMCF fits better to monophasic first-order profile more adequately than to zero-order profile, that of HAMC3 monophasic first-order, and that of HAMC to bi-phasic zero-order. Above results suggested that zero-order release rate can be achieved by adjusting the ratio of MTX-HSA conjugates to MTX in the preparation of HAMs such as HAMC3F.as HAMC3F.

• Journal of Pharmaceutical Investigation
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• 제15권2호
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• pp.53-62
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• 1985

Pivampicillin hydrochloride is a kind of broad spectrum antibiotics with bactericidal action, and is used in many countries, although it has bitter taste, unpleasant odour and side effects of irritating gastric mucosa, nausea, penicillin allergy, etc. For the improvement of such side effects of pivampicillin hydrochloride, microcapsules, with wall of ethylcellulose, have been prepared by coacervation method. The shape was observed through the scanning electron microscope, the release of the drug into an aqueous medium was studied and the effects of core: ethylcellulose ratio were interpreted as well as making sensory evaluation of taste and odour. There was decreasing trend in dissolution rate of the drug with the increase of core: ethylcellulose ratios, and the smaller microcapsules released their contents more rapidly. A linear relationship was established between the amount of ethylcellulose and the time for 60% release of the drug, and the release pattern was found to have similar characteristics to the release of the drug from an insoluble porous matrix. The release of the drug in the artificial intestinal fluids (pH 6.8) was found to be similar to that in water, while the release in the artificial gastric juice (pH 1.2) was slightly slower. Bioavailability of microcapsule was compared with that of pivampicillin hydrochloride in rabbits using serum concentration and urinary excretion measurements. Microcapsule gave showed slightly higher serum level than pivampicillin hydrochloride from 2 hours after administration, while no significant difference was observed in the accumulated urinary excretion rate between pivampicillin hydrochloride and microcapsule. The ulcer index of pivampicillin hydrochloride administered group was 2.6, and microcapsule administered group was 1.5, while control group was 0.8. Therefore it may be concluded that microencapsulation of pivampicillin hydrochloride is a useful pharmaceutical approach to protect the gastrointestinal tract from being injured by direct contact of pivampicillin hydrochloride without any significant difference of bioavailability.