• 셀메드
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• 제11권1호
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• pp.6.1-6.7
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• 2021

In situ gelling devices, as they enter the body, are dosage forms in the shape of the sol but turn into gel types under physiological circumstances. Transition from sol to gel is contingent on one or a mixture of diverse stimuli, such as transition of pH control of temperature, irradiation by UV, by the occurrence of certain ions or molecules. Such characteristic features may be commonly employed in drug delivery systems for the production of bioactive molecules for continuous delivery vehicles. The technique of in situ gelling has been shown to be impactful in enhancing the potency of local or systemic drugs supplied by non-parenteral pathways, increasing their period of residence at the absorption site. Formulation efficacy is further improved with the use of mucoadhesive agents or the use of polymers with both in situ gelling properties and the ability to bind with the mucosa/mucus. The most popular and common approach in recent years has provided by the use of polymers with different in situ gelation mechanisms for synergistic action between polymers in the same formulation. In situ gelling medicine systems in recent decades have received considerable interest. Until administration, it is in a sol-zone and is able to form gels in response to various endogenous factors, for e.g elevated temperature, pH changes and ions. Such systems can be used in various ways for local or systemic supply of drugs and successfully also as vehicles for drug-induced nano- and micro-particles. In this review we will discuss about various aspects about use of these in situ gels as novel drug delivery systems.

• Mass Spectrometry Letters
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• 제11권4호
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• pp.71-76
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• 2020

While montelukast (ML), a cysteinyl-leukotriene type 1 receptor (CysLT1) antagonist is widely used to treat symptoms of rhinitis or asthma, its formulations are mainly limited to solid preparation due to its instability. Recently, there have been attempts to develop various ML dosage forms, and this situation increases the demand of sensitive and creditable methods to determine ML in various samples such as plasma. Thus, here, a simple and efficient method to determine ML in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was presented. The mixture of DCM:EtOAc (25:75, v/v), the optimized extract solvent for LLE was found to be effective to extract ML without hydrophilic salts and proteins from the sample with limited volume. Also, the use of zafirlukast, instead of expensive ML-d6, as the internal standard makes the present method economical. The developed method was successfully validated in terms of selectivity, matrix effects (-14.8--6.9%), linearity (r230.998 within 0.5-500 ng/mL), sensitivity (the limit of detection and the lower limit of quantitation, ≤0.5 ng/mL), accuracy (88.4-100.6%), precision (3.0-13.3%), and recovery (80.8-86.3%) by following the FDA guidelines. Finally, the applicability of the validated method to pharmacokinetics (PK) studies was confirmed by the successful determination of PK parameters through it following oral administration of Singulair® granule in rats. Therefore, the present method can contribute to the development of new ML formulations through its performance to determine ML in rat plasma efficiently and sensitively.

• 셀메드
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• 제11권3호
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• pp.15.1-15.9
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• 2021

The chemical constitution of a drug has been accepted as an important basis for pharmacological action in Unani medicine. Various dosage forms have been developed on this concept, such as decoctions (Joshanda), infusions (Khesanda), extract (Rub / Usara), and syrup. Zarawand Mudaharaj (ZM.) / Aristolochia rotunda L. root was subjected to extraction process using Soxhlet's apparatus by using Response Surface Methodology (RSM) to design the number of random runs of the extracts with variation in the factors of temperature, the concentration of ethanol in water, time for extraction, for optimizing and maximizing the yield concentration. The data obtained, was analyzed with regression equation and ANOVA two-way summary to interpret the interaction of the factors for yield maximization. Minitab version 18 was used to design and analyze data. Validation of the optimum conditions for maximum yield of the whole extract of ZM. Root was carried out by re-run of the extract using the optimized conditions. The maximum yield percentage thus obtained using RSM was 20.87% whereas using these optimum conditions 21.35 % yield was obtained thereby validating the method. The association between the response functions and the process variables was identified by a three-factor recorded Box-Behnken design. In the present study RSM is used because itis a cheap and affordable method to optimize maximum yield percentage which may be reliably used by researchers. The study set in the surface conditions for ZM. root extraction by the Soxhlet apparatus for maximizing the yield percentage.

• Medical Lasers
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• 제10권1호
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• pp.22-30
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• 2021

Background and Objectives Ocular alkali burns cause severe damage to the ocular tissues and vision loss. Solcoseryl is a standardized calf blood extract that normalizes the metabolic disturbance and aids in maintaining the chemical and hormonal balance and has been used to treat burns in various tissues. This study examined the effects of Solcoseryl on a rat corneal alkali burn model. Materials and Methods Twenty rats were assigned randomly to four equal groups, including alkali burn, hyaluronic acid, Solcoseryl eyedrop, and Solcoseryl gel. A corneal alkali burn was induced by a NaOH-soaked paper disc. The treatments were given twice a day, every day. The wound area was measured after 24 and 48 hours, and the degree of neovascularization and corneal opacity were scored every week. The rats were sacrificed after three weeks for immunohistochemistry (IHC) to compare the level of inflammatory cytokines, IL-1β, IL-6, and TNF-α. The thickness of the retinal layers was compared to observe any changes in the retina. Results The use of Solcoseryl on corneal alkali burn accelerated wound healing with less neovascularization, greater opacity, and less cataract. IHC showed that the inflammation of the cornea was controlled by both the hyaluronic acid and Solcoseryl treatments. On the other hand, the inflammation had spread to the retina. When the dosage forms were compared, eyedrops were more effective on corneal inflammation, while the gel-type had a greater effect on retinal inflammation. Conclusion Solcoseryl was effective in accelerating the wound healing rate on a corneal alkali burn but could not prevent the spread of inflammation from the cornea to the retina. Eyedrops were more effective on inflammation in the cornea, and the gel was more effective in the retina.

• 한국산학기술학회논문지
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• 제17권9호
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• pp.228-234
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• 2016

본 이 연구의 목적은 이중 고온용융 압출법을 이용하여 기존의 방법으로 가지기 어려운 이상성의 약물방출 양상을 가지는 제형을 개발하는 것이다. 이 고온용융 압출물은 동회전 능을 가지는 두 개의 스크류가 장착된 압출기를 이용하여 제조되었다. Hydroxpropylmethylcellulose(HPMC) 같은 상대적으로 유리전이 온도가 높은 고분자를 이용하여 1차로 고온용융 압출물이 제조되었고, 이 1차 압출물과 상대적으로 유리전이 온도가 낮은 HPMC-AS(Acceate succinate)나 PEO(polyethlene oxide)를 이용하여 2차로 고온용융 압출물이 제조되었다. 또한 이중 고온용융 압출물과의 비교시험을 위해 같은 조성과 같은 조건하에서 일반적인 한 번의 고온용융 압출물도 제조되었다. 시차주사 열량계를 통해 물리적인 성질이 평가되었고, 미국약전의 제 1법에 따라 $37{\pm}0.5^{\circ}C$와 100 rpm의 조건에서 약물방출 시험이 진행되었으며 그 약물방출은 유사성인자($f_2$)를 이용하여 평가되었다. 시차주사 열량계 결과는 이부프로펜의 결정성이 이중 고온용융 압출법에서나 한번 고온용융 압출법 모두에서 무정형으로 변화된 것을 확인할 수 있었으며, 용출시험에서는 이중 고온용융 압출법에서 더욱 더 이상적인 이부프로펜의 방출을 인공위액(pH 1.2)에서 2시간, 0차 방출을 인공장액(pH 6.8)에서 6시간 동안 확인할 수 있었다. 빠른방출이 요구되는 글리메피라이드의 경우는 이중 고온용융 압출물에서는 60분에 80% 이상의 빠른 약물 방출을 보인 반면, 한번 고온용융 압출물에서는 약물방출이 HPMC와의 상호작용 때문에 느려져서 기준을 만족하지 못했다. 유사성 인자($f_2$) 값도 28.5로 매우 다른 방출을 보여주고 있음이 통계적으로 확인되었다. 이상의 결과들을 종합해 볼 때, 이중 고온용융 압출법은 완건성이 좋은 또 원하는 약물방출을 얻을 수 있는 방법이라 할 수 있다.

• 폴리머
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• 제32권4호
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• pp.328-333
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• 2008

삼투압을 이용한 약물전달시스템은 소화관내의 물이 다공성막을 통하여 시스템 내부로 침투하면 시스템 내부에 있던 삼투압물질과 섞여 삼투압을 발생시키고, 이 삼투압의 힘으로 시스템 내부에 있는 약물을 시스템 외부로 일정한 속도로 방출하는 제제기술이다. 이러한 삼투압을 이용하여 상용화된 대표적인 제품으로 니페디핀을 모델약물로 한 타블렛제형인 Procadia $XL^{(R)}$(Pfizer)과 $Adalat^{(R)}$(Bayer)가 널리 상용화되어 있다. 이번 연구에서는 타블렛 형태의 삼투압정을 유동층코팅 기술을 이용하여 삼투성펠렛으로 제조하였다. 삼투성펠렛은 수팽윤성 고분자와 삼투염을 포함한 시드층, 모델약물인 니페디핀을 포함하는 약물층 그리고 약물의 방출을 조절할 수 있는 다공성막으로 구성되어 있다. 본 연구에서는 다공성막으로 사용되는 초산셀룰로오스(CA)와 $Eudragit^{(R)}$ RS의 구성비와 코팅두께에 따른 약물방출 거동을 확인하였으며, 다공성막의 구성물질인 CA의 비가 증가할수록 또한 다공성막의 코팅두께가 증가할수록 같은 측정시간 때에 약물의 방출이 낮게 나타남을 확인하였다. 약물방출 전후의 펠렛의 형태를 확인하기 위하여 SEM을 측정하였다.

• Journal of Pharmaceutical Investigation
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• 제25권1호
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• pp.9-17
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• 1995

To stabilize omeprazole(OMP), ethylenediamine(ED) complex of omeprazole(OMPED) was prepared by reaction between OMP and ED in methanol, and the complex formation was confirmed by the instrumental analysis, i.e., IR, DSC, EA, NMR, MS and XRD. The rates of decomposition of OMP and OMPED in aqueous solution and the shelf lives at standard temperature were measured by accelerated stability analysis. The results are summarized as follows; The mole ratio of OMP and ED in OMPED complex is 1:1, the energy of formation within OMPED might be combined between polar imidazole group of OMP with induced a dipole amine group in the readily polarizable ED molecule. At standard temperature the degradation rate constant of OMP in aqueous solution is $2.540{\times}10^{-2}\;hr^{-1}$ and the shelf life is 4.15 hrs, and in the case of OMPED the degradation rate constant is $7.986{\times}10^{-4}\;hr^{-1}$ and the shelf life is 131.96 hrs. So, the OMPED has about 31 times longer shelf life than OMP. The activation energy of OMP and OMPED are 5.23 and 18.55 kcal $mole^{-1}$ respectively. The stability of OMP is dependent chiefly on pH in the solutions and it decomposes readily in acidic medium by hydrogen ion catalized reaction but becomes stable beyond pH 9.0. In case of the ED-complex, OMPED is stable in neutral as well as in dilute acidic solutions even in pH 6, OMPED is very stable to light(UV), that is, the rate constant and shelf life of OMP are $k=1.0188{\times}10^{-2}\;day^{-1}$, $T_{90%}=4.5 \;days$, on the other hand, the those of OMPED are $k=7.138{\times}10^{-4}\;day^{-1}$, $T_{90%}=64.1\;days$, respectively. From the above results, it is thought that new dosage forms could be developed by using the OMPED as a potential OMP complex.

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.29-36
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• 2009

Since the quality of final products is significantly affected by the homogeneity of powder mixture, the powder blending process has been regarded as one of the critical pharmaceutical unit processes, especially for solid dosage forms. Accordingly, the monitoring to determine a blending process' end-point based on a faster and more accurate in-line/on-line analysis has attracted enormous attentions recently. Among various analytical tools, NIR (near-infrared) spectroscopy has been extensively studied for PAT (process analytical technology) system due to its many advantages. In this study, NIR spectroscopy was employed with an optical fiber probe for the in-line monitoring of fluid-bed blending process. The position of the probe, the ratio of binary powder mixture, the powder size differential and the back-flush period of the shaking bag were examined as principal process parameters. During the blending process of lactose and mannitol powders, NIR spectra were collected, corrected, calibrated and analyzed using MSC and PLS method, respectively. The probe position was optimized. A reasonable end-point was predicted as 1,500 seconds based on 5% RSD value. As a consequence, it was demonstrated that the blending process using a fluid-bed processor has several advantages over other methods, and the application of NIRS with an optical fiber probe as PAT system for a fluid-bed blending process could be high feasible.

• 한국임상약학회지
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• 제24권1호
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• pp.26-32
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• 2014

Purpose: The aim of this study was to investigate drug prescription patterns for the treatment of asthma and chronic obstructive pulmonary disease (COPD) patients in Korea. Methods: Ambulatory adult patients who were diagnosed and received treatment for the asthma (ICD-10 code J45) or COPD (ICD-10 code J44) from January 2009 to September 2011 in two independent secondary hospitals in Korea were enrolled in this study. Prescribed drug lists were generated based on the evidence-based guidelines and prescribed drug dosage forms were identified from the patient medical records and computerized drug prescription databases of the study centers. Results: Total numbers of asthma and COPD patient enrolled in this study were 2,432 and 2,615, respectively. Individual prescription-based accumulated numbers of patient were 12,021 for asthma and 16,584 for COPD. The most commonly prescribed three drugs were oral predisolone, oral formoterol and oral montelukast for asthma and oral formoterol, oral doxofylline and inhaled tiotropium for COPD. Frequencies of oral drugs were 83.4% and 63.3% while inhalers were 16.4% and 30.2%, for asthma and COPD, respectively. Conclusion: The oral treatment was prescribed more in asthma and COPD patients than inhalers. To enhance the compliance of evidence-based guidelines for these chronic airway diseases, more realistic and specific strategies to increase the use of inhalers recommended as primary treatment options for asthma and COPD would be required.

• 대한화학회지
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• 제50권4호
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• pp.298-306
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• 2006

순수 형태 또는 약제 중 네오마이신과 스트렙토마이신을 신속하게 분석하는 인증된 분광광도법적 방법을 기술하였다. 이 방법은 산성 용액 속에서 기지 과량의 과망간산포타슘으로 약품을 산화시킨 다음 미반응의 과망간산을 아마란스(방법 A), 산성 오렌지 II(방법 B), 인디고카민(방법 C) 및 메틸렌블루(방법 D) 색소로 각각 lmax=521, 485, 610 및 664 nm에서 흡광도를 측정하여 정량하는 방법이다. 네오마이신과 스트렙토마이신의 농도 범위 5-10 및 2-7 mg mL-1에서 Beer의 법칙이 성립되었으며 겉보기 몰흡수계수와 sendell 감도 값은 네오마이신과 스트렙토마이신에 대하여 각각 5.47-6.20´104, 2.35-2.91´105 L mol-1 cm-1 및 7.57-8.59, 5.01-6.2 ng cm-2 였다. 반응에 영향을 미치는 여러 변수를 조사하여 최적화하였으며 이 방법을 순수 Çü태 × 약제 Çü태의 약품에 적용하여 좋은 Á확도와 정밀도로 정량하였다. á제의 방해는 관찰되지 않았으며 얻어진 결과는 공인 석법을 사용하여 얻은 aacute;과와 잘 일치하였다.