• Korean Journal of Clinical Pharmacy
• /
• v.15 no.1
• /
• pp.34-40
• /
• 2005

We examined the effects of food on pharmacokinetic and pharmacodynamic properties of fenofibrate released from sustained-release(SR) capsule as therapy for hypolipidemia. Twenty-four healthy volunteers were used in $3{\times}3$ crossover pharmacokinetic and pharmacodynamic study; Additional six volunteers were used as a control group (i.e., no fenofibrate administration). A single dose of fenofibrate (SR capsule, 250 mg) was administered on three occasions: after overnight fasting, after consumption of a standard breakfast, and after a high-fat breakfast. Serial blood samples were collected for the next 72 hours. Plasma fenofibric acid concentrations were measured by high performance liquid chromatography, and pharmacokinetic parameters were calculated using ADAPT II program. Plsama triglyceride concentrations were measured by blood chemistry analyzer (CH-100). The pharmacokinetic parameters were significantly affected by food intake. The high-fat breakfast affected the rate of absorption of fenofibrate more than did the standard breakfast and fasted conditions. Plasma concentrations of triglyceride at 24 hours decreased significantly after the administration of fenofibrate compared with the concentration at 0 hours(P<0.05). In healthy volunteers, the bioavailability of fenofibrate was greater when administered via sustained-release capsules immediately after the consumption of food than after fasting condition.

• Korean Journal of Veterinary Research
• /
• v.39 no.2
• /
• pp.267-275
• /
• 1999

Bovine somatotropin is known to improve the growth rate and lactation in cattle. In this study, we examined the concentration-time profiles of a sustained-release formulation of bovine somatotropin (BST) and insulin-like growth factor-1 (IGF-1) in plasma and milk in cows. In addition, the possible effect of co-administrated vitamin ADE complex on the pharmacokinetic parameters of BST and IGF-1 was evaluated. 1. Plasma BST and IGF-1 levels reached the peak at 12~24 and 48 hours after the administration of BST, and plasma half-lives ranged 100 to 137 and 201 to 310 hours, respectively. To 8th day after administration, BST and IGF-1 levels in milk were not significantly different from the control levels. 2. Plasma BST levels showed cyclic pattern with high concentrations in early stage after each injection and following gradual declining during repeated administrations at 2 week intervals, while plasma IGF-1 levels in treated animals did not show such a cyclic pattern, but remained higher than the control levels. 3. Milk BST and IGF-1 levels during repeated treatments were not significantly different from the control levels. 4. Co-administration of vitamin ADE complex yielded slightly increased AUC of plasma BST for high dose group, but such effect was not evident in the IGF-1 levels. Co-administration of ADE complex tended to increase plasma BST levels and decrease the elimination half-life of IGF-1. 5. These results suggest that the BST formulation tested is one of the ideal sustained-release formulation for long term use in dairy industry. As for the co-administration of vitamin ADE complex, the benefit of co-administration with BST is needed to be further evaluated.

• Journal of Pharmaceutical Investigation
• /
• v.32 no.3
• /
• pp.165-172
• /
• 2002

Injectable gel composed of egg phosphatidylcholine (egg PC), hyaluronate (HA) and water was formulated for local drug delivery. The lamellar liquid crystalline structure of the egg PC/water system did not change by adding HA in the formulation. However, egg PC/HA/water gel was more resistant to erosion than the egg PC/water gel. The egg PC/HA/water and egg PC/water gels containing model drugs, tetracycline and sudan IV were prepared to perform in vitro and in vivo drug release experiments. In vitro release of tetracycline was sustained in the gel type formulations. The release rate of hydrophobic sudan IV was extremely slow. More than 99% of sudan IV remained inside the gel after 5 days. In vivo release of drugs from the air pouch model in Balb/c mice shows that lipophilic sudan IV remained for more than 10 days whereas tetracycline remained for 1 day in the pouch. The compatibility of the gels was also examined by histopathology. The gels did not cause any adverse inflammatory effect in the air pouch.

• Journal of Pharmaceutical Investigation
• /
• v.36 no.2
• /
• pp.109-114
• /
• 2006

Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were developed for sustained delivery of water-soluble macromolecules. PLGA nanoparticles were fabricated by spontaneous emulsification solvent diffusion method generating negatively charged particles and heterogeneous size distribution. As a model drug, blue dextran was encapsulated in PLGA nanoparticles. In addition, nanoparticles were also prepared with varying ratio of poloxamer 188 (P188) and poloxamer 407 (P407), and coating with poly(vinyl alcohol) (PVA). Then, the particle size, zeta potential and encapsulation efficiency of nanoparticles containing blue dextran were studied. In vitro release of blue dextran from nanoparticles was also investigated. The surface and morphology of nanoparticles were characterized by scanning electron microscopy (SEM). In case of nanoparticles prepared with PLGA, P407, and different organic solvents, particle size was in the range of $230{\sim}320\;nm$ and zeta potentials of nanoparticles were negative. The SEM images showed that ethyl acetate is suitable for the formulation of PLGA nanoparticles with good appearance. Moreover, ethyl acetate showed higher encapsulation efficiency than other solvents. The addition of P188 to formulation did not affect the particle size of PLGA nanoparticles but altered the release patterns of blue dextran from nanoparticles. However, PVA, as a coating material, altered the particle size with increasing the PVA concentration. The nanoparticles were physically stable in the change of particle size during long-term storage. From the results, the PLGA nanoparticles prepared with various contents of poloxamers and PVA, could modulate the particles size of nanoparticles, in vitro release pattern, and encapsulation of water-soluble macromolecules.

• YAKHAK HOEJI
• /
• v.36 no.3
• /
• pp.212-219
• /
• 1992

Although oral route is the most convenient route for drug administration, the short and variable transit of drug through GI tract restricts the sustained drug absorption after oral administration. Thus, for sustained absorption of drugs, it is desirable to prolong the GI transit time by retaining the dosage forms in the stomach. In this study, the enzyme-digestible swelling hydrogel was synthesized by heating the mixed solution of N-vinyl-2-pyrrolidone[monomer], acrylated albumin[crosslinking agent] and proxyphylline[drug] at $65^{\circ}C$ for 10 hours in the cylindrical test tube. The resultant hydrogel tablet (diameter; 0.77 cm, thickness; 0.47 cm) was designed to swell in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the drug release. After releasing drug, the hydrogel was expected to be degraded by pepsin, an enzyme in the stomach, and eventually solubilized. Actually, the hydrogel synthesized in the study swelled to a size larger than the diameter of the pylorus ($1.3{\pm}0.7$ cm) and slowly digested in the presence of pepsin. Drug release from the hydrogel was prolonged up to about 12 hours. The swelling kinetics was dependent on albumin acrylation time, drug content and gel thickness. Particularly the gel thickness was the most important factor that influences on drug release. By adjusting these factors, the albumin-crosslinked hydrogel was expected to be retained in the stomach for up to 60 hours and used as a potential platform of drugs for long-term GI absorption.

• Journal of Dairy Science and Biotechnology
• /
• v.23 no.2
• /
• pp.115-123
• /
• 2005

Microcapsules consisting of natural, biodegradable polymers for controlled and/or sustained core release applications are needed. Physicochemical properties of whey proteins suggest that they may be suitable wall materials in developing such microcapsules. The objectives of the research were to develop water-insoluble, whey protein-based microcapsules containing a model water-soluble drug using a chemical cross-linking agent, glutaraldehyde, and to investigate core release from these capsules at simulated physiological conditions. A model water soluble drug, theophylline, was suspended in whey protein isolate (WPI) solution. The suspension was dispersed in a mixture of dichloromethane and hexane containing 1% biomedical polyurethane. Protein matrices were cross-linked with 7.5-30 ml of glutaraldehyde-saturated toluene (GAST) for 1-3 hr. Microcapsules were harvested, washed, dried and analyzed for core retention, microstructure, and core release in enzyme-free simulated gastric fluid (SGF) and simulated intestinal fluid(SIF) at $37^{\circ}C$. A method consisting of double emulsification and heat gelation was also developed to prepare water-insoluble, whey protein-based microcapsules containing anhydrous milkfat (AMF) as a model apolar core. AMF was emulsified into WPI solution (15${\sim}$30%, pH 4.5-7.2) at a proportion of 25${\sim}$50%(w/w, on dry basis). The oil-in-water emulsion was then added and dispersed into corn oil ($50^{\circ}C$) to form an O/W/O double emulsion and then heated at $85^{\circ}C$ for 20 min for gelation of whey protein wall matrix. Effects of emulsion composition and pH on core retention, microstructure, and water-solubility of microcapsules were determined. Overall results suggest that whey proteins can be used in developing microcapsules for controlled and sustained core release applications.

• YAKHAK HOEJI
• /
• v.43 no.2
• /
• pp.150-159
• /
• 1999

Hollow type suppositories inserted polyvinyl alcohol (PVA) hydrogel capsule containing propranolol·HCI (PPH) were prepared using different bases, polyethylene glycol (PEG), Witepsol H-15 (WH-15) and Witepsol W-35 (WW-35) to improve the controlled release of PPH. The release of PPH from the hollow type suppository inserted PVA hydrogel capsule was retarded than that from PEG, WH-15, or WW-35 hollow type suppositories in rat rectal cavity. When the suppositories were administered to rats, the controlled release of PPH was proved by the plasma concentration-time-profiles of PPH. No significant difference (p〈0.05) among the three different hollow type suppositories was observed in terms of AUC and MRT of PPH. WH-15 hollow type suppository inserted 12% of PVA hydrogel capsule caused irritation to rat rectal mucosa. However, the WH-15 hollow type suppository inserted PVA hydrogel capsule caused no severe irritation on rectal mucosa. The application of the hollow type suppositories using PVA in sustained rectal delivery of drugs might be feasible.

• Journal of Pharmaceutical Investigation
• /
• v.27 no.4
• /
• pp.303-311
• /
• 1997

Proliposomal patch of clenbuterol, ${\beta}_2-agonist$ bronchodilator, was prepared and its feasibility as a novel transdermal drug delivery system was examined. Proliposomal granules containing clenbuterol was prepared by a standard method using sorbitol and lecithin with (Rx 2) or without cholesterol (Rx 1). The porous structure of sorbitol in the proliposomes was maintained allowing tree flowability of the granules. Following contact with water, the granules were converted probably to liposomes almost completely within several minutes. It indicates that proliposomes may be hydrated, when they are applied on the skin under occlusive condition in vivo, by the sweat to form liposomes. Clenbuterol release from Rx 1 and Rx 2 proliposomes to pH 7.4 isotonic phospate buffer (PBS) across cellulose membrane (mol. wt. cut-off of 12000-14000) was retarded significantly compared with that from the mixture of clenbuterol powder and blank proliposomes. Interestingly, proliposomes prepared with lecithin and cholesterol (i.e., Rx 2 proliposomes) showed much more retarded release of clenbuterol than proliposomes prepared only with lecithin (i.e.. Rx 1 proliposomes), indicating that clenbuterol release from proliposomes can be controlled by the addition of cholesterol to the proliposomes. Proliposomal patches were prepared using PVC film as an occlusive backing sheet, two sides adhesive tape (urethane, 1.45 mm thickness) as a reservoir for proliposome granules and Millipore MF-membrane (0.45 mm pore size) as a drug release-controlling membrane. Rx 1 or Rx 2 proliposomes containing 4.6 mg of clenbuterol were loaded into the reservoir of the patch. Clenbuterol release from the patches to pH 7.4 PBS was determined using USP paddle (50 rpm)-over-disc release method. Clenbuterol release from the proliposomal patches was much more retarded even than from a matrix type clenbuterol patch (Boehringer Ingelheim ltd). Being consistent with clenbuterol release from the proliposomal granules, the release from the patches was highly dependent on the presence of cholesterol in the proliposomes : Patches containing Rx 2 proliposomes showed several fold slower drug release than patches containing Rx 1 proliposomes. When the patch containing Rx 1 proliposomes was applied on to the back of a hair-removed rat, clenbuterol concentration in the rat blood was maintained during 6-72 hrs. Transdermal absorption of clenbuterol from the patch was accelerated when the patch was prehydrated with 50 ml of pH 7.4 PBS before topical application. Above results indicate that sustained transdermal delivery of clenbuterol is feasible using proliposomal patches if the cholesterol content and pore size of the release rate-controlling membrane of patches, for example, are appropriately controlled.

• Journal of Pharmaceutical Investigation
• /
• v.20 no.2
• /
• pp.89-95
• /
• 1990

Ethylcellulose-PEG 4000 film coated on core tablets was investigated as a potential drug delivery system for the controlled release of chlorpheniramine maleate (CPM). The kinetic analysis of the release data indicated that CPM release followed a diffusion-controlled model, where the quantity released per unit area is proportional to the square root of time. The effect of the film composition, CPM concentration, plasticizer concentration and CPM solubility on the release characteristics were examined. The release rate constant increased as CPM concentration increased. It also increased as the PEG 4000 content in the film increased above 10%(w/w), however, it decreased as the PEG 4000 content increased in the concentration range below 10%(w/w). The release rate constant was not affected by the coated weight on the core tablet. The film-coated tablets which contain CPM only in the coated film layer seemed to be a potential oral drug delivery system for the controlled release of CPM.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.230.1-230.1
• /
• 2003

In case of oral application of quinupramine, antidepressants, it may cause adverse effects such as diarrhea, nausea due to transient high blood concentration. Ethylene vinyl acetate (EVA) which is heat-processible, flexible, inexpensive material was used for transdermal drug delivery. The purpose of this study was to develop the new transdermal delivery system of quinupramine using EVA polymer matrix that can provide sustained release and avoid the side effects. The EVA matrix containing quinupramine was prepared by solvent-evaporation method. (omitted)