• Journal of Pharmaceutical Investigation
• /
• 제22권3호
• /
• pp.205-210
• /
• 1992

In order to develop a controlled-release oral drug delivery system (DDS) of theophylline (TP), microporous membrane-coated tablets were prepared and evaluated in vitro and in vivo. Rapidly water-soluble core tablets of TP (300 mg) were prepared by wet granulation and compression technique, Then the core tablets were spray-coated with polyvinylchloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of coating suspensions on the pharmaceutical characteristics such as membrane strength and dissolution was investigated in vitro. The membranes remained unbroken in pH 1.2 buffer at $37^{\circ}C$ at least for 2 hours after the disintergration test. TP was released from the coated-released tablets at a zero-order rate over 8 hours. The release at pH 1.2 and 4.0 was similar in rate but a little more rapid than that at pH 6.8. The coated tablets were administered to three healthy male volunteers and their saliva profiles of TP were compared with those from the commercial sustained release TP tablets such as Slobid and Asconthin. Saliva TP concentrations from the coated tablets were successfully sustained over 48 hours after the dosing and were comparable to those of the commercial sustained-release tablets. The membrane-coating technique is very simple and does not need any sophisticated equipments. In this respect, the membrane-coated tablets may be superior to the commercial sustained-release tablets and this technique is worth adopting by the pharmaceutical industries.

• 폴리머
• /
• 제25권3호
• /
• pp.334-342
• /
• 2001

항생제의 서방형 전달을 위해 황산겐타마이신 gentamicin sulfate (GS)을 함유한 poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) 제형을 제조하였다. 본 연구에서는 제형의 두께, hydroxyvalerate (HV) 농도, 초기 약물함유량 및 첨가제의 함유에 따른 약물 방출거동의 변화를 조사하였다. 전자주사현미경을 이용하여 제형의 표면형태와 매트릭스 내부 약물의 조성을 관찰한 결과 약물방출 전과 후 모두 거칠고 다공성인 형태를 가짐을 알 수 있었다. 또한, HV와 첨가제의 함량이 증가할수록 약물이 고분자 매트릭스에 더 조밀하게 배열함을 관찰하였고, 이러한 구조가 약물의 방출에 영향을 미침을 알았다. HPLC를 이용하여 약물의 방출량을 측정한 결과, 모든 제형이 복합적인 방출 방향을 나타내었고, 일부 매트릭스는 30일 동안 거의 영차에 가까운 방출거동을 보였다. 이상의 결과에서 우리는 제형의 두께, 고분자 매트릭스의 조성, 첨가제의 함유량 등을 조절함으로 약물 방출을 제어할 수 있음을 확인하였다.

• 대한의생명과학회지
• /
• 제13권3호
• /
• pp.175-182
• /
• 2007

In vitro ciprofloxacin (CFX)-release study and bioassay using microorganisms were performed to estimate the retention of the antimicrobial activity of the CFX-incorporated central venous catheters (CFX-CVCs). The release experiments were carried out under the optional CFX-release conditions to mimic the in vivo environment. The release of CFX experienced an initial burst followed by a slow and steady matrix-diffusion controlled release. The 1.0CP (polyurethane catheter containing 1.0% (w/w) of CFX) under dynamic condition showed a near zero-order CFX release profile, which is beneficial for the long-tenn antimicrobial activity. The modified Kirby-Bauer method was performed employing S. aureus and E. coli to evaluate the retention of antimicrobial activity of the catheters retrieved from the release experiments. The 1.0CP showed the long-term antimicrobial activity (${\geq}\;21$ days) against both S. aureus and E. coli. These results indicate that 1.0CP is useful as a long-tenn indwelling CVC.

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

• Journal of Pharmaceutical Investigation
• /
• 제41권4호
• /
• pp.217-225
• /
• 2011

The aim of this work was to prepare porous osmotic pump tablets for controlled delivery of Aceclofenac. Aceclofenac solid dispersion was prepared to improve the solubility by using the drug - carrier (Mannitol) ratio of 1:1. The osmotic pump tablets were prepared using the solid dispersed product of Aceclofenac. The formulation contains potassium chloride as osmotic agent, cellulose acetate as semipermeable membrane, poly ethylene glycol (PEG 4000) as pore former and sodium lauryl sulphate (SLS) as solubility enhancer. The formulations were designed by the general factors such as osmotic agent and pore former. All formulations were evaluated for various physical parameters and, the in vitro release studies were conducted as per USP. The drug release kinetic studies such as zero order, first order, and Higuchi and Korsmeyer peppas were determined and compared. All the formulations gave more controlled release compared to the marketed tablet studied. Numerical optimization techniques were applied to found out the best formulation by considering the parameter of in vitro drug release kinetics and dissolution profile standards. It was concluded that the porous osmotic pump tablets (F7) composed of Aceclofenac solid dispersion/Potassium chloride/Lactose/Sodium lauryl sulphate/Magnesium Stearate (400/40/95/10/5, mg/tab) and coating composition with Cellulose acetate/ PEG 4000 (60/40 %w/w) is the most satisfactory formulation. The porous osmotic pump tablets provide prolonged, controlled, and gastrointestinal environment-independent drug release.

• Journal of Pharmaceutical Investigation
• /
• 제28권2호
• /
• pp.87-92
• /
• 1998

Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of the skin irritancy and the instability against the pH, temperature, and light. In order to overcome these problems, various topical gels and multiple emulsion creams which can control the release of active ingredient, KA, were formulated employing cream bases of mineral oil with caprylic capric triglyceride and hydrophilic polymers such as chitosan, carbopol. and pluronics. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solution. Drug release from chitosan-based gels (ChitoGel) obeyed to the first order kinetics with a rapid release especially in the initial period. However, pluronic-based gels (PluGel) and carbopol-based gels (CarboGel) revealed controlled release of drug to some extent, followed by the square root-time kinetics. Moreover, the release of KA was further controlled with the W/O/W multiple emulsion creams (MultiCream), showing the apparent zero order release kinetics by virtue of dynamic ratecontrolling membrane of the oil layer. The flux $(J,\;{\mu}g/cm^2/hr)$ of ChitoGel. CarboGel. PluGel. and MultiCream in the initial period of 6hr were 73.30, 28.67. 24.04 and 7.72, respectively. On the other hand, the skin irritancy score of ChitoGel and MultiCream were observed as 2.5 and 2.3 respectively, in the rabbit skin irritation test. Although there were insignificant differences at p<0.05 between those formulations, it was possible to conclude that the W/O/W multiple emulsion creams containing KA might be a good candidate for an antimelanogenic drug delivery system due to the controlled release of acidic drug molecules.

• Journal of Pharmaceutical Investigation
• /
• 제22권2호
• /
• pp.133-137
• /
• 1992

A novel oral controlled release tablet which may offer more uniform drug level in the body than simple zero-order was developed. The tablet is composed of three layers; outer film layer, middle part compression-coated hydroxypropylmethylcellulose (HPMC) matrix layer, and inner core layer. Each layer contains nicardipine HCl as a model drug. In vitro dissolution test showed that the tablet released the drug in clear three steps; a rapid initial release, followed by a constant rate of release, and then a second phase of fast release of drug. The dissolution characteristics could be modified easily by changing the grade of HPMC, thickness of matrix layer, content of methylcellulose in matrix layer, content of active ingredient in each layer. The pH of dissolution medium did not affect the release profile. This three-step release system is expected to raise the blood concentration rapidly to effective level and to maintain effective blood level longer than simple slow-release systems.

• Journal of Pharmaceutical Investigation
• /
• 제34권6호
• /
• pp.471-475
• /
• 2004

Tamsulosin has been frequently used for the treatment of benign prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin matrix tablets and assess their formulation variables. We designed enteric coated sustained-release tamsulosin matrices to fulfill above statement. Aqueous microchannels in the enteric film need to be formed in order to obtain tamsulosin release even in an acidic environment such as gastric region. In the sustained-release tamsulosin matrix, low viscosity hydroxypropylmethylcellulose was used as a rate controller. Povidone K30 was also added to the matrices to facilitate water uptake so that a decrease in the release rate of tamsulosin as time elapses was prevented, possibly leading to pseudo zero-order release of the drug. The matrices were enteric-coated with hydroxypropylmethylcellulose phthalate (HPMCP), along with povidone K30 as an aqueous microchannel former. With the aqueous microchannels formed within the enteric film, tamsulosin could be released in an acidic condition. The release of tamsulosin decreased with increasing thickness of HPMCP membrane while the release rates of tamsulosin from those having different HPMCP thickness in pH 7.2 aqueous media were not considerably different, indicating that the enteric film was promptly dissolved at pH 7.2. These results clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the KFDA.

• Journal of Pharmaceutical Investigation
• /
• 제19권3호
• /
• pp.145-154
• /
• 1989

Methyl methacrylate-butyl methacrylate copolymer (MMBM)-povidone (PVP) films were investigated as a potential topical drug delivery system for the controlled release of econazole nitrate as a model drug. The effect of changes in film composition, drug concentration, film thickness, pH and temperature of release medium on the in vitro release of econazole nitrate were studied. The release rate constant was found to be increased with increasing povidone content in dry films. Drug release followed zero-order kinetics in the initial stage and then release rate increased gradually with time, espicially in the films having larger proportions of PVP. The release rate was found to be dependent on drug content, film thickness, the pH and temperature of release medium. Antimicrobial test showed that microbial growth was inhibited markedly with increasing proportions of PVP in films. Also drug content and film thickness affected the antimicrobial activity.

• Journal of Pharmaceutical Investigation
• /
• 제31권1호
• /
• pp.19-25
• /
• 2001

The purpose of this study was to use a ternary polymeric matrix system for high drug loading of a highly soluble drug for controlled release delivery. The controlled drug delivery of diltiazem HCl (solubility > 50% in water at $25^{\circ}C$) with high loading dose (the final loading dose of drug was 34%) from a ternary polymeric matrix (gelatin, pectin, HPMC) was successfully accomplished. This simple monolithic system with 240 mg drug loading provided near zero-order release over a 24 hour-period by which time the system was completely dissolved. The release kinetics of diltiazem HCl tablet with high loading dose from the designed ternary polymeric system was dependent on the ratios of HPMC : pectin binary mixture. The release rate increased as pectin : HPMC ratio were increased. Swelling behavior of the ternary system and the ionic interaction of formulation components with cationic diltiazem molecule appear to control drug diffusion and the release kinetics. Comparable release profiles between commercial product and the designed system were obtained. The binding study between gelatin with diltiazem HCl showed the presence of two binding sites for drug interaction with subsequent controlled diffusion upon swelling. This designed delivery system is easy to manufacture and drug release behavior is highly reproducible and offers advantages over the existing commercial product.