설린닥의 경구용 지속성 제제설계 및 용출특성

이계주,박선희,서성수,황성주 충남대학교 약학대학 의약품개발연구소 1997 藥學論文集 Vol.13 No.-

Sustained release matrix tablets, pellets, and coated pellets for the delivery of sulindac were prepared using cellulose derivatives at various ratios, and evaluated for the dissolution pattern. The release of sulindac from matrix tablets prepared with low viscosity HPMC was relatively fast, and especially the tablets made of Metolose SM released all of sulindac within 1hr. The release of drug from tablets made of other HPMC derivatives were retarded in the order of the following: Pharmacoat 645>Pharmacoat 606>Pharmacoat 606+HPC-L>HPC-L. The most sustained release pattern was observed with the preparation of high viscous polymer. Metolose 90SH. While release of sulindac from matrix type pellet containing 10 ㎎/cap of Metolose 90 SH or 60SH was completed within 1hr, a prolonged release formulation (30% in 1 hr) was obtained by the inclusion of EC. Pellets coated with HPMC showed a fast release pattern (≥80% within 2hrs), whereas pellets coated with HPMC and EC (molar ratio 1:1) showed a sustained release pattern (≥80% in 12 hrs), with the release from EC pellets being the most sustained. Fast (naked) and slow release pellets coated with EC. Metolose 60SH 50cps and propyleneglycol, and enteric pellets coated with HPMCP 55 and Myvacet? were prepared, and combined at various ratios for the assessment of dissolution pattern. The result indicates the possibility that the development of 24 hr sustained release delivery systems containing sulindac for oral administration could be achieved by means of combining sustained and fast release pellets at a proper portion.

설린닥의 경구용 지속성 제제설계 및 용출특성

이계주(Gye Ju Rhee),박선희(Sun Hee Park),서성수(Sung Su Suh),황성주(Sung Joo Whang) 대한약학회 1997 약학회지 Vol.41 No.1

Sustained release matrix tablets, pellets, and coated pellets for the delivery of sulindac were prepared using cellulose derivatives at various ratios, and evaluated for the dissolution pattern. The release of sulindac, from matrix tablets prepared with low viscosity HPMC was relatively fast, and especially the tablets made of Metolose SM released all of sulindac within 1 hr. The release of drug from tablets made of other HPMC derivatives were retarded in the order of the following: Pharmacoat 645>Pharmacoat 606>Pharrnacoat 606+HPC-L>HPC-L. The most sustained release pattern was observed with the preparation of high viscous polymer. Metolose 90 SH. While release of sulindac, from matrix type pellet containing 10mg/cap of Metolose 90 SH or 60 SH was completed within 1 hr, a prolonged release formulation (30% in 1 hr) was obtained by the inclusion of EC. Pellets coated with HPMC showed a fast release pattern (> or = 80% within 2 hrs), whereas pellets coated with HPMC and EC (molar ratio 1 : 1) showed a sustained release pattern (> or = 80% in 12 hrs), vath the release from EC pellets being the most sustained. Fast (naked) and slow release pellets coated with EC, Metolose 60SH 50cps and propylene glycol. and enteric pellets coated with HPMCP 55 and Myvacet(R) were prepared, and combined at various ratios for the assessment of dissolution pattern. The result indicates the possibility that the development of 24 hr sustained release delivery systems containing sulindac for oral administration could be achieved by means of combining sustained and fast release pellets at a proper portion.

Matrix Properties of a New Plant Gum in Controlled Drug Delivery

V. D. Kalu,M. A. Odeniyi,K. T. Jaiyeoba 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.7

A new plant gum, Okra (extracted from the pods of Hibiscus esculentus), has been evaluated as a controlled-release agent in modified release matrices, in comparison with sodium carboxymethyl cellulose (NaCMC) and hydroxypropylmethyl cellulose (HPMC), using Paracetamol as a model drug. Tablets were produced by direct compression and the in-vitro drug release was assessed in conditions mimicking the gastro intestinal system, for 6 h. Okra gum matrices provided a controlled-release of Paracetamol for more than 6 h and the release rates followed time-independent kinetics. The release rates were dependent on the concentration of the drug present in the matrix. The addition of tablet excipients, lactose and Avicel, altered the dissolution profile and the release kinetics. Okra gum compared favourably with NaCMC, and a combination of Okra gum and NaCMC, or on further addition of HPMC resulted in near zeroorder release of paracetamol from the matrix tablet. The results indicate that Okra gum matrices could be useful in the formulation of sustained-release tablets for up to 6 h.

Matrix Properties of a New Plant Gum in Controlled Drug Delivery

Kalu, V.D.,Jaiyeoba, K.T.,Odeniyi, M.A. 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.7

A new plant gum, Okra (extracted from the pods of Hibiscus esculentus), has been evaluated as a controlled-release agent in modified release matrices, in comparison with sodium carboxymethyl cellulose (NaCMC) and hydroxypropylmethyl cellulose (HPMC), using Paracetamol as a model drug. Tablets were produced by direct compression and the in-vitro drug release was assessed in conditions mimicking the gastro intestinal system, for 6 h. Okra gum matrices provided a controlled-release of Paracetamol for more than 6 h and the release rates followed time-independent kinetics. The release rates were dependent on the concentration of the drug present in the matrix. The addition of tablet excipients, lactose and Avicel, altered the dissolution profile and the release kinetics. Okra gum compared favourably with NaCMC, and a combination of Okra gum and NaCMC, or on further addition of HPMC resulted in near zero-order release of paracetamol from the matrix tablet. The results indicate that Okra gum matrices could be useful in the formulation of sustained-release tablets for up to 6 h.

Preparation, In vitro, Preclinical and Clinical Evaluations of Once Daily Sustained Release Tablets of Aceclofenac

Naha, A.,Usha, A.N.,Ranjith, A.K.,Musmade, P.,Manoj, K.,Anju, P.,Prasanna, S.,Mutalik, S. 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.2

The objective of the present study was to develop ‘once daily’ sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose-K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drugexcipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, In vitro drug release and stability studies. Preclinical (anti-inflammatorv, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45%) and MCC (30%) along with talc and magnesium stearate (1% w/w, each) (tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with bodyweight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters.

소수성 고분자를 이용한 미라베그론 함유 서방성 정제의 개발

심주아,송세현 한국산학기술학회 2022 한국산학기술학회논문지 Vol.23 No.5

This study was conducted on a hydrophobic, polymer-containing, sustained-release (SR) tablet containing mirabegron (MRB), which is used to treat the symptoms of overactive bladder usually in elderly patients. The developed sustained-release formulation was designed as a hydrophobic matrix using Kollidon® SR. We evaluated the solubilization characteristics and compatibilities of several surfactants, and Kolliphor® P407 was selected as the solubilizing agent. Pharmatose® 200M, A-Tab®, and Avicel® PH-101 were used as excipients for tablets, and their effects on drug release were evaluated by dissolution testing. MRB release from SR tablets was found to be dependent on Kollidon® SR and A-Tab® contents. Dissolution tests were performed in water and pH 6.8 media to confirm the effect of pH changes in dissolution media on the drug release rate of SR tablets, and similar dissolution patterns were observed in both media as indicated by a similarity factor (f2) of 68, which was calculated using dissolution data. The study shows that the developed SR matrix tablet could be utilized as an effective drug delivery system for the oral administration of MRB. 본 연구의 목적은 소수성 고분자를 이용하여 미라베그론을 함유하는 경구용 서방성 정제를 개발하는 것이다. 미라베그론은 과민성 방광증상의 치료에 사용되는 약물로 용해도는 pH 의존적이며, 낮은 pH에서 높은 용해도를 나타낸다. 미라베그론의 물에 대한 낮은 용해도를 개선하기 위해 다양한 계면활성제를 대상으로 가용화 능력을 평가하고, 계면활성제와 미라베그론과의 배합적합성 시험을 통해서 가용화제로 Kolliphor® P407을 선정하여 정제의 제조에 사용하였다. 정제는 습식과립법으로 제조된 과립물과 방출 조절 고분자인 Kollidon® SR을 혼합한 후, 원형으로 압축하여 제조하였다. 수용성인 Pharmatose®, 수불용성인 A-Tab®, 팽윤성의 Avicel® PH-101를 정제의 부형제로 사용하고, 이들이 약물 방출에 미치는 영향을 용출시험으로 평가하였다. Kollidon® SR의 사용량이 증가할수록 약물 방출이 지속되었으며, 수불용성 부형제인 A-Tab®의 사용량이 증가할수록 소수성 매트릭스의 형태를 유지하는 시간이 증가하였다. 약물 방출을 4시간 이상 지속하는 서방성 정제를 대상으로 서로 다른 매질에서 용출시험한 후, 유사인자(f2=68)를 산출하여 약물방출의 유사성을 확인하였다. 본 연구결과를 통해 확보된 서방성 매트릭스 정제는 미라베그론의 경구투여를 위한 효과적인 약물전달시스템으로 응용될 수 있을 것으로 기대된다.

Preparation and evaluation of once-daily sustained-release coated tablets of tolterodine-L-tartrate

( Roshan Pradhan ),( Yong Ll Kim ),( Sun Woo Chang ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

In this study, once-daily, sustained-release matrix tablets of tolterodine l-tartrate (TOL) for treatment of overactive bladder (OAB) were prepared by direct compression using various amounts of hydrophilic polymers such as HPMC 2910 and HPMC 2208 along with other tablet excipients; the tablets were then coated. In vitro dissolution studies were carried out under different pH conditions. The dissolution data were fitted into zero-order, first-order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. Among the four formulations (F1-F4), the dissolution profiles of formulation F2 were most similar to the marketed product with similarity and difference factors of 70.25 and 1.59 respectively. Furthermore, pharmacokinetic studies were carried out in healthy human volunteers after oral administration of the prepared TOL sustained-release matrix-coated tablet and the marketed product. The results revealed that the pharmacokinetic parameters of AUC, Cmax, Tmax, t1/2, Kel, and MRT of TOL for the developed formulation (F2) were not significantly different from that for the marketed product, suggesting that they were bioequivalent. Therefore, the developed sustained-release tablet formulation of TOL could be an alternative dosage form to the SR capsule for treatment of OAB.ⓒ2013 Elsevier B. V.All rights reserved.

니페디핀 서방성 정제의 제제설계

최옥,김승수,박은석,지상철 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.2

Matrix tablets of nifedipine (NP) were prepared with Eudragit, diluent (lactose or Ca. phosphate) and Mg. stearate employing two different preparation methods (wet granulation and direct compression) to develop its sustainedrelease dosage forms. The effects of various formulation factors on the dissolution rate of the drug were investigated. Dissolution test was studied in pH 6.8 phosphate buffer containing 1 % sodium lauryl sulfate using the paddle method. Formulation factors were the type and content of Eudragit, the type of diluent and the tablet preparation method. The optimum formula of NP matrix tablet, which resulted in a similar dissolution profile to that from Adalat Oros used as a reference, was 30 mg NP, 10% Eudragit RS, 2% Mg. stearate and an adequate quantity of lactose to yield 500 mg weight using the wet granulation method.

Hydroxypropyl methylcellulose를 활용한 비타민 C 지속성 정제의 용출 특성 분석

차자현(Ja Hyun Cha),홍준기(Jun Kee Hong),이성완(Sung Wan Lee),차재욱(Jae Uk Cha),고원화(Won Hwa Ko),백현호(Hyon Ho Baek),박현진(Hyun Jin Park) 한국식품과학회 2012 한국식품과학회지 Vol.44 No.3

본 연구에서는 널리 사용되는 수용성 비타민인 비타민 C의 지속성 특성을 발현시키기 위해 HPMC를 사용하여 정제를 제조하였다. 먼저 비타민 C 지속성 정제의 효과적인 용출실험을 진행하기 위해서 용출 용매에 비타민 C의 산화를 방지할 수 있는 항산화제를 첨가함으로써 수분에 의한 비타민 C의 분해를 방지하였다. 비타민 C 지속성 정제의 용출 거동을 확인하기 위해「대한약전 9개정」과「경구용의약품의 용출규격 설정 가이드라인」의 용출시험법과「건강기능식품이 기준 및 규격 고시전문(제2009-153호)」에 근거하여 함량시험과 시간별 용출률을 분석하였다. 분석된 용출 거동은 zero-order release model과 Korsmeyer-Peppas model에 의해 겔 내에서의 활성 성분의 확산과 겔층의 소실로 인한 이의 유리 메카니즘이 분석되었다(37,38). 비타민 C 지속성 정제에 사용된 지속성 HPMC의 사용량이 증가할수록 위장관 운동의 영향에 관계없는 zero-order release의 용출 거동에 가까워짐을 확인하였다. 이는 정제에 사용된 HPMC의 사용량이 높을수록 물을 흡수하여 초기에 겔을 형성하는 속도가 빨라져 용출 속도가 감소함을 보여준다. 점도에 따른 차이는 비타민 C의 높은 수용성 성질 때문에 차이를 보이지 않았으나, 난용성 유효 성분을 적용한 처방에서는 수화능과 겔 형성능에 따라 점도별로 차이가 날것으로 사료된다. 이는 Korsmeyer-Peppas model에 의한 메커니즘분석에서 비타민 C의 겔 내 활성 성분의 확산이 겔 층의 소실로 인한 유리보다 다소 우세한 것으로 설명될 수 있다. 이러한 결과를 바탕으로 비타민 C는 수분에 대한 안정성이 부족함에도 지속성 정제로의 개발 및 용출분석이 가능하며, 지속성 고분자로 사용된 HPMC의 사용량에 따라 용출 거동을 조절할 수 있어 1일 2회 내지 1일 1회 요법의 비타민 C 지속성 정제의 제제화와 안정적인 용출분석을 수행할 수 있다. 건강기능식품에 고시된 비타민 C의 정량법인 HPLC법 및 본 연구를 통해 차이가 없음이 확인된 UV spectrophotometer를 사용한 평가방법을 통해 보다 편리하게 수행할 수 있다. The objective of this study was to develop oral matrix tablets for the sustained release of vitamin C. In this study hydroxypropyl methylcellulose (HPMC) has been utilized as an excipient, as it is one of the most widely used polymers, for use during long periods of time in formations. The vitamin C tablet formulation depends on the molecular weight and concentration of sustained-delivery in HPMC. Anti-oxidants have been added as a dissolution medium in order to prevent vitamin C degradation in water. The dissolution test was carried out in a distilled water medium, and the release model equation was applied to analyze the vitamin C release pattern. The results demonstrated that the release and lasting power of vitamin C tablets, containing HPMC, lasted for more than 12 h.

Gum odina: a novel matrix forming material for sustained drug delivery

Dinda, Subas Chandra,Mukherjee, Biswajit,Samanta, Amalesh 경희한의학연구센터 2011 Oriental Pharmacy and Experimental Medicine Vol.11 No.2

The study concerns the evaluation of natural gum odina as novel sustained release matrix forming material in tablet formulation. Matrix tablets were prepared by wet granulation technique. Diclofenac sodium was used as model drug. The tablet weight (250 mg) and diameter (9 mm) was kept constant. The tablets were evaluated for physicochemical properties, drug content uniformity and in vitro drug release kinetics. The effect of gum concentration (10, 20, 30 and 50% $w/w$ with respect to total tablet weight) on in-vitro drug release profile was examined and compared with diclofenac sodium (Voveran SR-100), the slow release marketed formulation developed in India. The drug-gum (excipient) interactions using FTIR (Furrier Transform Infrared) spectrum ensures its safe use as matrix forming material. The prepared matrix formulations were found to be having near zero order release kinetics of diclofenac sodium with good strength and acceptable physicochemical properties. The formulations were found to be sustained delivery of the drug up to 24 h. The $t_{1/2}$ of the various matrix tablets (with 10%, 20%, 30% and 50% $w/w$ of gum odina) found to be more than 11 h, where as that of the marketed formulation (Voveran SR) found to be 8 h. It has been found that as the %ge of gum increases the retardation of drug release from the formulation also increases. The matrix tablet with 20% $w/w$ of gum odina was found suitable to formulate swelling controlled matrix that releases the drug by diffusion. It is concluded that the gum odina possess substantial matrix forming property that could be used for sustained drug delivery.