Retarded Dissolution of Ibuprofen in Gelatin Microcapsule by Cross-Linking with Glutaradehyde

Chul-Soon Yong,Dong-Xun Li,Dong-Hoon Oh,Jung-Ae Kim,Bong-Kyu Yoo,우종수,이종달,최한곤 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.6

Ibuprofen-loaded gelatin microcapsule, a solid form of microcapsules simultaneously containing ethanol and ibuprofen in water-soluble gelatin shell was previously reported to improve the dissolution of drug. In this study, to retard the initial high dissolution of ibuprofen from gelatin microcapsule, the ibuprofen-loaded cross-linked gelatin microcapsule was prepared by treating an ibuprofen-loaded gelatin microcapsule with glutaraldehyde and its dissolution was evaluated compared to ibuprofen powder and gelatin microcapsule. The ibuprofen-loaded crosslinked microcapsule treated with glutaraldehyde for 10 and 60 sec gave significantly higher dissolution rates than did ibuprofen powder. Furthermore, the dissolution rate of ibuprofen from the cross-linked microcapsule treated for 10 sec was similar to that from gelatin microcapsule. However, the dissolution rate of ibuprofen from the cross-linked microcapsule treated for 60 sec decreased significantly compared to gelatin microcapsule, suggesting that the treatment of gelatin microcapsule with glutaraldehyde for 60 sec could cross-link the gelatin microcapsule. Furthermore, the cross-linking of gelatin microcapsule markedly retarded the release rate of ibuprofen in pH 1.2 simulated gastric fluid compared to gelatin microcapsule. However, the cross-linking of gelatin microcapsule with glutaraldehyde hardly changed the size of gelatin microcapsules, ethanol and ibuprofen contents encapsulated in gelatin microcapsule. Thus, the ibuprofen-loaded cross-linked gelatin microcapsule could retard the initial high dissolution of poorly water-soluble ibuprofen.

Enhanced Oral Bioavailability of Ibuprofen in Rats by Poloxamer Gel Using Poloxamer 188 and Menthol

Yong, Chul Soon,Lee, Mi-Kyung,Park, Young-Joon,Kong, Kyung-Hwan,Xuan, Jing Ji,Kim, Ji-Hyun,Kim, Jung-Ae,Lyoo, Won Seok,Han, Sung Soo,Rhee, Jong-Dal,Kim, Jong Oh,Yang, Chae Ha,Kim, Chong-Kook,Choi, Han Taylor Francis 2005 Drug development and industrial pharmacy Vol.31 No.7

<P>To improve the oral bioavailability of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the ibuprofen-loaded preparations composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed an abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/mL. The simultaneous addition of menthol and poloxamer 188 significantly improved the dissolution rates of ibuprofen from aqueous solution due to the ibuprofen solubility-improving effect of menthol in the presence of poloxamer. Furthermore, the ibuprofen-loaded preparation with menthol and poloxamer 188 gave significantly higher initial plasma concentrations, Cmax, and AUC of ibuprofen than did the preparation without menthol and poloxamer 188, indicating that the simultaneous addition of menthol and poloxamer 188 could improve the oral bioavailability of ibuprofen in rats. In modern pain management it is always desirable for the ibuprofen-loaded preparation with poloxamer 188 and menthol to show a rapid onset of action with a minimal phase of lag time to feel the decreased pain. From an industry point of view, it is more desirable for a formulation to be fast acting, easy to use, and cost effective. Thus, the ibuprofen-loaded preparation with poloxamer 188 and menthol was a more effective oral dosage form for poorly water-soluble ibuprofen.</P>

Retarded Dissolution of Ibuprofen in Gelatin Microcapsule by Cross-Linking with Glutaradehyde

Yong, Chul-Soon,Li, Dong-Xun,Oh, Dong-Hoon,Kim, Jung-Ae,Yoo, Bong-Kyu,Woo, Jong-Soo,Rhee, Jong-Dal,Choi, Han-Gon The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.6

Ibuprofen-loaded gelatin microcapsule, a solid form of microcapsules simultaneously containing ethanol and ibuprofen in water-soluble gelatin shell was previously reported to improve the dissolution of drug. In this study, to retard the initial high dissolution of ibuprofen from gelatin microcapsule, the ibuprofen-loaded cross-linked gelatin microcapsule was prepared by treating an ibuprofen-loaded gelatin microcapsule with glutaraldehyde and its dissolution was evaluated compared to ibuprofen powder and gelatin microcapsule. The ibuprofen-loaded crosslinked microcapsule treated with glutaraldehyde for 10 and 60 sec gave significantly higher dissolution rates than did ibuprofen powder. Furthermore, the dissolution rate of ibuprofen from the cross-linked microcapsule treated for 10 sec was similar to that from gelatin microcapsule. However, the dissolution rate of ibuprofen from the cross-linked microcapsule treated for 60 sec decreased significantly compared to gelatin microcapsule, suggesting that the treatment of gelatin microcapsule with glutaraldehyde for 60 sec could cross-link the gelatin microcapsule. Furthermore, the cross-linking of gelatin microcapsule markedly retarded the release rate of ibuprofen in pH 1.2 simulated gastric fluid compared to gelatin microcapsule. However, the cross-linking of gelatin microcapsule with glutaraldehyde hardly changed the size of gelatin microcapsules, ethanol and ibuprofen contents encapsulated in gelatin microcapsule. Thus, the ibuprofen-loaded cross-linked gelatin microcapsule could retard the initial high dissolution of poorly water-soluble ibuprofen.

극소 저출생 체중아의 동맥관 개존증의 치료에 사용되는 경구용 Ibuprofen과 정주용 Indomethacin의 효과 비교

이지형,최민환,심규홍,송영환,최명재 대한신생아학회 2013 Neonatal medicine Vol.20 No.1

Purpose: Ibuprofen and indomethacin has been used in treatment of patent ductus arteriosus (PDA) in Korea. But, there were few reports about oral ibuprofen for the treatment of PDA. We aimed to evaluate the efficacy and safety of oral ibuprofen versus intravenous indomethacin for the treatment of PDA in very low birth weight (VLBW) infants. Methods: A retrospective study of VLBW infants treated with oral ibuprofen or intravenous indomethacin for symptomatic PDA at Inje University Sanggye Paik Hospital between February 2002 and April 2012 was performed. Results: We identified 43 infants that received oral ibuprofen and 9 infants that received intravenous indomethacin. There were no significant differences in the efficacy and safety between oral ibuprofen group and intravenous indomethacin group. There was no significant difference between the use of oral ibuprofen before 48 hours after birth and after 48 hours the efficacy and safety. Conclusion: In our study, oral ibuprofen appears to be as effective as intravenous indomethacin for the treatment of PDA in VLBW infants with similar complication rates. 목적: 극소 저체중 출생아 동맥관 개존증의 약물 치료로 경구용 ibuprofen과 정주용 indomethacin의 효과 및 부작용을 비교분석해 보고 경구용 ibuprofen군 내에서도 48시간 이전에 사용한 경우와 이후에 사용한 경우를 나누어 각 군에서의 효과와 부작용의 차이를 조사하여 경구용 ibuprofen 제제의 효용성과 치료 시기 결정에 대한 실마리를 얻고자 하였다. 방법: 2002년 2월부터 2012년 4월까지 인제대학교 상계백병원 소아청소년과에서 출생한 재태연령 32주 미만이면서 출생체중 1,500 g 미만인 신생아 중 혈역학적으로 의미 있는 동맥관 개존증으로 치료받은 52명 중 정주용 indomethacin 투여군 9명과 경구용 ibuprofen 투여군 43명을 대상으로 약물의 효능과 부작용을 후향적인 방법으로 조사하여 비교 분석하였다. 결과: 각 군에서 첫 번째 주기 약물 치료 후 반응을 보인 환아는 정주용 indomethacin 투여군 전체 9명 중 7명, 경구용ibuprofen 투여군 43명 중 35명으로 유의한 차이가 없었다(77.8% vs 81.3%, P=0.802). 부작용 측면에서도 유의한 차이는 없었다. 경구용 ibuprofen 투여군 내에서 48시간 이전에 사용한 경우와 48시간 이후에 사용한 경우 효능과 부작용측면에서의 유의한 차이는 없었다. 결론: 극소저체중 출생아에 있어 동맥관 개존증의 치료에 경구용 ibuprofen이 정주용 indomethacin에 비해 효능과 부작용 면에서도 유의한 차이가 없는 것으로 보임에 따라 저렴하면서도 간단하게 사용할 수 있는 경구용 ibuprofen의 사용이 권장될 수 있겠다.

미숙아 동맥관 개존증의 예방적 치료로서 Indomethacin과 Ibuprofen의 효과

전복선,권경아,박경희,변신연,김묘징 대한신생아학회 2011 Neonatal medicine Vol.18 No.2

Purpose: The aim of our study was to compare the efficacy and safety of ibuprofen and indomethacin in the prophylaxis of patent ductus arteriosus (PDA) in preterm infants and to determine whether ibuprofen could be an alternative agent in prophylactic use. Methods: A retrospective study including 37 preterm infants <1,500 g of birth weight, <34 weeks of gestation, whom were administrated indomethacin (n=17; January 2009-December 2009) or ibuprofen (n=20; January 2010-February 2011) within 24 hr after birth was conducted. The rate of ductal closure, need for surgical ligation, clinical outcomes such as necrotizing enterocolitis,intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity (ROP) and death rate were compared. Results: There were no statistically significant differences between the two groups in mean gestational age, mean birth weight,Apgar score, sex, type of delivery, maternal dexamethasone treatment, frequency and duration of ventilator and surfactant treatment. The closure of PDA on day 7 of life was in 19 of 20 infants of the ibuprofen group and 13 of 17 infants of the indomethacin group (P=0.159). Between the two groups, there were no significant differences with respect to clinical outcomes. Conclusion: Ibuprofen has similar effects to indomethacin in the rate of PDA closure. Our study demonstrates that prophylactic ibuprofen is relatively effective without significant differences with respect to clinical outcomes compared with indomethacin. Therefore, ibuprofen may be used as an alternative agent in the prophylaxis of PDA in preterm infants. 목적: Indomethacin은 미숙아 동맥관 개존증의 예방적 용법및 치료적 용법에 사용되어 왔다. 하지만 최근에는 indomethacin의국내 보급이 중단됨에 ibuprofen이 사용되고 있다. Ibuprofen은 동맥관 폐쇄에 indomethacin만큼 효과적이며 부작용은 적은 것으로 알려져 있다. 그러나 ibuprofen의 예방적용법에 관한 연구는 많지 않다. 본 연구에서는 미숙아에서 동맥관 개존증의 예방적 치료에 대한 ibuprofen의 효과와 안정성을indomethacin과 비교하여 분석하고자 하였다. 방법: 2009년 1월부터 2009년 12월, 그리고 2010년 1월부터2011년 2월까지 두 기간동안 3개의 참여 대학병원 신생아 중환자실에 입원한 34주 미만, 1,500 g 미만의 신생아 중에서 생후24시간 이내에 indomethacin이나 ibuprofen이 예방적 목적으로 투여된 환자를 대상으로 하여 의무기록을 후향적으로 검토하였다. 두 군간의 동맥관 폐쇄에 대한 효과와 주산기 합병증의발생 정도를 조사하였다. 결과: 두 군간에 환아의 성별, 재태 연령, 출생체중, 분만 방법,1분 및 5분 Apgar 점수, 산모의 steroid 사용 여부, 폐 표면활성제 사용 여부 및 인공호흡기 사용여부 및 사용기간에 있어 유의한 차이는 없었다. 생후 7일에 시행한 심초음파 검사에서indomethacin군은 17명 중 13명, ibuprofen군은 20명 중 19명이 동맥관의 폐쇄를 보였다. 총 입원 기간 외에 주산기 합병증의빈도는 두 군간의 유의한 차이가 없었다. 결론: Ibuprofen의 예방적 사용은 동맥관 폐쇄에 효과적이며주산기 합병증 측면에서 유의한 부정적인 차이가 없었다. 따라서 indomethacin을 대체하여 ibuprofen의 사용을 고려해 볼수 있겠다.

호흡곤란 증후군 미숙아에서 동맥관 개존증의 약물 치료 : 경구용 ibuprofen과 indomethacin의 비교

이수진,김지영,손세정,박은애 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.9

Purpose:Indomethacin is widely used for the prophylaxis and treatment of patent ductus arteriosus (PDA); however, it is associated with side effects such as renal failure, intraventricular hemorrhage, and gastrointestinal bleeding. Intravenous ibuprofen has been shown to be as effective as indomethacin in prompting PDA closure. If treatment with oral ibuprofen is as effective as indomethacin, it would have the advantages of greater availability, simpler administration, and lower cost. We conducted this study to compare the efficacy and side effects of indomethacin with those of oral ibuprofen, vis-à-vis on the pharmacological closure of PDA. Methods:As a randomized double-blind study, 34 preterm infants with respiratory distress syndrome and hemodynamically significant PDA were treated with either intravenous indomethacin or oral ibuprofen. Echocardiography was performed by one cardiologist who was blind to the treatment that any given infant received. The rate of ductal closure, the need for additional drug treatment or surgical ligation, clinical outcome, and the side effects of drug treatment were compared. Results:Ductal closure occurred in 16 of 18 patients (88.9%) from the indomethacin group and in 14 of 16 patients (87.5%) from the ibuprofen group (P>0.05). Three patients in the indomethacin group and four in the ibuprofen group required a second drug treatment (P>0.05). Three patients (i.e., one patient in the indomethacin group and two in the ibuprofen group) underwent surgical ligation (P>0.05). Between the two groups, there was no significant difference vis-à-vis in side effects or clinical outcome. Conclusion:Compared to indomethacin, oral ibuprofen has the advantages of simpler administration and lower cost, while being as effective; in addition, there are no differences between the two drug treatments with regards to side effects or clinical outcomes. Therefore, the widespread use of oral ibuprofen should be considered in treating PDA in preterm infants. (Korean J Pediatr 2008;51:956-963) Purpose:Indomethacin is widely used for the prophylaxis and treatment of patent ductus arteriosus (PDA); however, it is associated with side effects such as renal failure, intraventricular hemorrhage, and gastrointestinal bleeding. Intravenous ibuprofen has been shown to be as effective as indomethacin in prompting PDA closure. If treatment with oral ibuprofen is as effective as indomethacin, it would have the advantages of greater availability, simpler administration, and lower cost. We conducted this study to compare the efficacy and side effects of indomethacin with those of oral ibuprofen, vis-à-vis on the pharmacological closure of PDA. Methods:As a randomized double-blind study, 34 preterm infants with respiratory distress syndrome and hemodynamically significant PDA were treated with either intravenous indomethacin or oral ibuprofen. Echocardiography was performed by one cardiologist who was blind to the treatment that any given infant received. The rate of ductal closure, the need for additional drug treatment or surgical ligation, clinical outcome, and the side effects of drug treatment were compared. Results:Ductal closure occurred in 16 of 18 patients (88.9%) from the indomethacin group and in 14 of 16 patients (87.5%) from the ibuprofen group (P>0.05). Three patients in the indomethacin group and four in the ibuprofen group required a second drug treatment (P>0.05). Three patients (i.e., one patient in the indomethacin group and two in the ibuprofen group) underwent surgical ligation (P>0.05). Between the two groups, there was no significant difference vis-à-vis in side effects or clinical outcome. Conclusion:Compared to indomethacin, oral ibuprofen has the advantages of simpler administration and lower cost, while being as effective; in addition, there are no differences between the two drug treatments with regards to side effects or clinical outcomes. Therefore, the widespread use of oral ibuprofen should be considered in treating PDA in preterm infants. (Korean J Pediatr 2008;51:956-963)

1,250 g 미만 미숙아에서 예방적 Ibuprofen의 효과

여문수,최경빈,이현주,박현경,김창렬,설인준 대한신생아학회 2011 Neonatal medicine Vol.18 No.2

Purpose: Ibuprofen is used for prevention and treatment of patent ductus arteriosus as an alternative drug of indomethacin in very premature infants. We aimed to determine the effect of prophylactic ibuprofen on patent ductus arteriosus and clinical outcomes in preterm infants less than 1,250 g. Methods: A retrospective review of 39 preterm infants who were admitted to our neonatal intensive care unit from November 2009to July 2010 was performed. Patients were divided into a prophylactic group (n=13) and a matched historical control group (n=26),where prophylactic ibuprofen were administrated within 24 hours after birth. The rate of ductal closure, side-effects of drug treatment and clinical outcomes were compared between two groups. Results: Comparison of the prophylactic and control groups revealed no significant differences in the rate of ductal closure (69.2%vs 77.7%, P=0.825) and surgical ligation (23.1% vs 30.8%, P=0.719). Occurrence of bowel perforation was more frequent in the prophylactic group than the control group, but was not significant (30.8% vs 11.5%, P=0.194). The frequency of intraventricular hemorrhage (grade≥3) and other outcomes did not differ between the groups. Conclusion: Ibuprofen prophylaxis in preterm infants did not decrease the rate of ductal closure, the need for surgical ligation and the incidence of intraventricular hemorrhage. Further studies are needed to investigate the beneficial effect and associated adverse events attributed to ibuprofen prophylaxis. 목적: 최근 indomethacin의 대체약으로 ibuprofen이 미숙아동맥관 개존증의 예방과 치료에 사용되고 있다. 본 연구는 1,250g 미만의 미숙아를 대상으로 ibuprofen의 예방적 치료 효과 및임상 경과를 분석하고자 하였다. 방법: 2009년 11월부터 2010년 7월까지 본원 신생아 중환자실에 입원한 1,250 g 미만의 동맥관 개존증 환아 39명을 대상으로 후향적으로 의무기록을 조사하였다. Ibuprofen의 예방적 투여군(출생 후 24시간 이내에 ibuprofen 투여) 13명에 대해 재태연령과 출생체중을 과거 대응(historical match)하여 대조군 26명으로 분류하였고, 두 군의 동맥관 개존증 빈도, 임상 경과 및합병증을 분석하였다. 결과: Ibuprofen을 투여한 예방적 투여군과 대조군 간의 동맥관 폐쇄율(69.2% vs 77.7%, P=0.825)은 유의한 차이가 없었고,ibuprofen 치료에 실패하여 동맥관 결찰술을 시행 받은 경우도두 군간에 유의한 차이가 없었다(23.1% vs 30.8%, P=0.719). 약물과 관련된 부작용으로 위장관 천공이 발생한 경우는 예방적투여군에서 더 많은 경향을 보였으나 대상수의 부족 등으로 통계적 유의성은 없었다(30.8% vs 11.5%, P=0.194). 뇌실 내 출혈(grade≥3) 및 다른 미숙아 합병증의 발생률도 두 군간 차이는없었다. 결론: 미숙아에서 ibuprofen의 예방적인 투여가 동맥관 폐쇄율, 동맥관 결찰술 그리고 고도의 뇌실 내 출혈의 빈도를 감소시키지 못하였다. 향후 예방적 ibuprofen 사용과 관련하여 효과및 부작용에 대한 더 많은 연구가 되어야 할 것이다.

Effect of Additive of the Encapsulated Amounts and Solubility of Poorly Water-soluble Ibuprofen in Gelatin Microcapsules

Li, Dong Xun,Park, Jung-Gil,Han, Hong-Hee,Yang, Chan-Woo,Choi, Jun-Young,Oh, Dong-Hoon,Yong, Chul-Soon,Choi, Han-Gon The Korean Society of Pharmaceutical Sciences and 2007 Journal of Pharmaceutical Investigation Vol.37 No.5

Poorly water-soluble ibuprofen and ethanol can be encapsulated in gelatin microcapsule by spray drying technique. To select an optimal formula of ibuprofen-loaded gelatin microcapsule which increased the ethanol content and ibuprofen solubility with the decreased amount of gelatin in the microcapsules, in this study, the effect of gelatin, ibuprofen and sodium lauryl sulfate on the ibuprofen solubility and the amount of ethanol and ibuprofen encapsulated in the gelatin microcapsule were investigated. Ibuprofen solubility and the amount of ethanol encapsulated increased as gelatin and sodium lauryl sulfate increased, reached maximum at 4% and 0.6%, respectively and then followed a rapid decrease. Furthermore, the ibuprofen solubility and the encapsulated ibuprofen content increased as the amount of ibuprofen increased, reaching maximum at 0.5% and beyond that, there was no change in the solubility and ibuprofen content. However, the encapsulated ethanol content remained same irrespective of the amount of ibuprofen. On the basis of increased ibuprofen solubility, our results showed that the formula of ibuprofen-loaded gelatin microcapsule at the ratio of gelatin/ibuprofen/sodium lauryl sulfate/water/ethanol of 4/0.5/0.6/30/70 with ibuprofen solubility of about $290\;{\mu}g/mL$ and ethanol content of about $160\;{\mu}g/mg$ could be a potential oral delivery system for poorly water-soluble ibuprofen.

동맥관개존증이 있는 미숙아에서 ibuprofen 치료 실패의 위험인자

권남희 ( Nam Hee Kwon ),이지훈 ( Ji Hoon Lee ),전가원 ( Ga Won Jeon ),신종범 ( Jong Beom Sin ) 대한주산의학회 2014 Perinatology Vol.25 No.4

목적 : 재태 연령 32주 미만의 미숙아에서 혈역학적으로 유의한 동맥관 개존증이 진단되어 prostaglandin 합성 억제제를 투여한 후에도 약 20-30%는 약물에 반응하지 않고 동맥관 개존증이 지속되어 추가 치료가 필요하다. 따라서 본 연구에서는 미숙아에서 동맥관 개존증의 치료를 위해 투여한 ibuprofen의 치료 실패와 관련된 인자에 대해 알아보고자한다. 방법 : 2010년 1월부터 2012년 12월까지 인제대학교 부산백병원 신생아 집중 치료실에 입원한 재태 연령 32주 미만의미숙아들 중 심초음파를 통해 혈역학적으로 유의한 동맥관 개존증이 진단 되어 ibuprofen을 사용한 125명을 대상으로ibuprofen 치료 후 동맥관이 폐쇄된 반응군과 ibuprofen 투여 후에도 혈역학적으로 유의한 동맥관이 지속되는 비반응군의 임상특성과 비반응군의 위험인자를 알아보았다. 결과 : 총 125명 중 반응군 I은 59%, 비반응군 I은 41% 이고, 두 번째 주기 ibuprofen을 투약한 36명 중 반응군 II는39%, 비반응군 II는 61% 였다. 비반응군 I/II는 반응군 I/II에 비해 출생 체중이 작고 재태 연령이 어렸으며 72% (37/51)에서 동맥관 결찰 수술이 필요하였다. 비반응군 I에서 인공호흡기 치료 기간이 길었고 호흡기 질환으로 인한 스테로이드투여가 더 많았으며 재원기간이 길었다. 비반응군 II에서 진단 당시 동맥관 직경이 크고, 저혈압으로 인한 승압제 사용이많았다. 결론 : 재태 연령이 어리고 출생 체중이 작을수록 ibuprofen에 대한 동맥관의 반응이 낮았다. 큰 동맥관 직경과 저혈압으로 인한 승압제 사용은 동맥관 개존증에서 ibuprofen을 이용한 약물 치료 실패의 위험인자로 고려할 수 있다. 이는향후 추가 연구를 통해 수술적 치료 여부 및 시기를 결정하는데 도움될 것으로 생각된다. Purpose : In this study, the risk factors of failure of ibuprofen treatment in preterm infants with hemodynamicallysignificant patent ductus arteriosus (hsPDA) were investigated. Methods : Among 403 preterm infants (<32 weeks gestation) born between January 2010 and December 2012,125 infants treated with ibuprofen for hsPDA were retrospectively reviewed. The preterm infants were dividedinto the following groups according to their response to the 1st and 2nd cycles of ibuprofen treatment: respondergroups I and II, closure of the ductus arteriosus after the 1st and 2nd cycles of ibuprofen treatment; and nonrespondergroups I and II, persistency of hsPDA after the 1st and 2nd cycles of ibuprofen treatment. Results : One hundred twenty five infants were enrolled in the study: 74 in responder group I, 51 in non-respondergroup I, 14 in responder group II, and 22 in non-responder group II. In non-responder group I, the gestational ageand birth weight were smaller, the postnatal steroid treatment was more frequent, and the duration of mechanicalventilation and the days spent in the hospital were prolonged.I n non-responder group II, the gestational age andbirth weight were smaller, the diameters of the ductus arteriosus were larger, and the inotropics use was morefrequent. Conclusion : Failure of ibuprofen treatment of hsPDA is associated with the diameter of the ductus arteriosusand with inotropics use. Obtaining data regarding these is expected to help in determining if early direct surgicalligation is needed.

Preparation and characterization of ibuprofen-loaded alginate microspheresusing ethylenediamine as a crosslinker

Sabyasachi Maiti,Biswanath Sa 경희대학교 융합한의과학연구소 2008 Oriental Pharmacy and Experimental Medicine Vol.8 No.2

In this study, ionotropic gelation method was used for the preparation of ibuprofen-loaded calcium alginate (CALG) and ethylenediamine (EDA) treated calcium alginate (EDA-CALG) microspheres. The effect of EDA-treatment on drug entrapment efficiency, particle size, morphology, swelling behavior and in vitro release characteristics of the microspheres was investigated by varying its concentration from 0.5 to 2% (v/v). The reduction in drug entrapment efficiency by a maximum of 44.60% was noted for EDA-CALG microspheres compared to untreated CALG microspheres. The particle size and swelling index of EDA-CALG microspheres were reduced with increasing EDA concentration. All the microspheres were observed to retain their spherical shapes with rough surfaces. EDA-CALG microspheres prepared using 1% and 2% v/v EDA, released almost all of its content within 7 h in pH 6.8 phosphate buffer, however, CALG microspheres were found to release the same within 3 h. The intensity of melting endothermic peak of ibuprofen reduced significantly at lower drug load as experienced from DSC thermograms. The FT-IR spectrum of pure ibuprofen, ibuprofen-loaded CALG and EDA-CALG microspheres showed the characteristic band of C = O stretching vibration of ibuprofen. Hence, this study revealed that EDA can be employed for the preparation of ibuprofen-loaded CALG microspheres to retard the drug release to some extent. In this study, ionotropic gelation method was used for the preparation of ibuprofen-loaded calcium alginate (CALG) and ethylenediamine (EDA) treated calcium alginate (EDA-CALG) microspheres. The effect of EDA-treatment on drug entrapment efficiency, particle size, morphology, swelling behavior and in vitro release characteristics of the microspheres was investigated by varying its concentration from 0.5 to 2% (v/v). The reduction in drug entrapment efficiency by a maximum of 44.60% was noted for EDA-CALG microspheres compared to untreated CALG microspheres. The particle size and swelling index of EDA-CALG microspheres were reduced with increasing EDA concentration. All the microspheres were observed to retain their spherical shapes with rough surfaces. EDA-CALG microspheres prepared using 1% and 2% v/v EDA, released almost all of its content within 7 h in pH 6.8 phosphate buffer, however, CALG microspheres were found to release the same within 3 h. The intensity of melting endothermic peak of ibuprofen reduced significantly at lower drug load as experienced from DSC thermograms. The FT-IR spectrum of pure ibuprofen, ibuprofen-loaded CALG and EDA-CALG microspheres showed the characteristic band of C = O stretching vibration of ibuprofen. Hence, this study revealed that EDA can be employed for the preparation of ibuprofen-loaded CALG microspheres to retard the drug release to some extent.