• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.155-165
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• 1994

Some mucoadhesive polymers such as hydroxypropylcelluose (HPC) and carbopol-934 (CP) have been employed for the preparation of mucoadhesive polymeric systems, and their physical properties including mucoadhesion, swelling, and drug release were evaluated. A new simple experimental technique that can quantitatively measure the bioadhesive properties of various polymeric systems has been developed by the methods of detachment force test. As the polymeric systems, the discs of freeze-dried HPC/CP solid dispersions were prepared. The mucosa used in these tests were upper, middle, and lower parts of small intestine of male rats weighing $300{\sim}350\;g$. Detachment forces were increased as the mole fraction of CP increased in discs of HPC/CP solid dispersions. In the points of intestinal site dependence of mucoadhesion, the solid dispersions revealed non-specific mucoadhesion to the intestine. Swelling and drug release characteristics of mucoadhesive polymeric systems were studied extensively to find out the feasibility for the oral controlled delivery systems. Swelling ratio, expressed as the final height/initial height, has been determined in various pH buffer solutions. Hydrochlorothiazide (HCT) was employed as a model drug for release study. Apparent swelling and drug release rate constants, $K_s$ and $K_r$ respectively, were obtained from the square-root time plot of either swelling ratio or released amount of drug, particularly for the time periods before reaching the equilibrium. As a result, the swelling ratio of HPC/CP solid dispersions was increased as the weight percentage of CP increased. Similarly, the release of HCT from the solid dispersions was dependent on pH changes and CP contents, resulted in the slower release of HCT with the increases of pH and CP contents.

• Journal of Biomedical Engineering Research
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• v.23 no.3
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• pp.189-196
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• 2002

Transdermal drug delivery offers an alternative method to the conventional oral and injection delivery method. Its advantages include its ability to deliver drugs directly into systemic circulation. However, there have been restrictions in its application to deliver drugs because of the skin's barrier function. In this study, we try to combine a Sonophoresis and oxygen Pressure method in order to increase the Permeability of the skin. we used water as the compound and by utilizing the skin impedance method. we measured the hydration Permeability of skin Ultrasound was applied using a sonicator(Solcare-U1000. Solco, Korea) operating at a frequency of 1MHz. oxygen Pressure was applied using a compressor(Oxyjet-Pointer, Nora Bode. Germany) operating at a pressure of 2Bar/cm2. Experiment was performed in vivo for 42 People. We divided the subjects into four smaller groups. A different transdermal drug delivery method was applied for each group on the back of their hand. We measured the skin impedance variations on the hand. during a 20-minute time Period. The control group did not show any significant increase or variation of skin impedance to water. In comparison to the control group(Passive diffusion) the hydration Permeability of the ultrasound group and the oxygen Pressure group was approximately 25 and 30 times higher consecutively. Futhermore, the hydration permeability of the combination of ultrasound and oxygen Pressure group was about 70-fold higher in comparison to the control group(passive diffusion) . The results reveal that a combination of ultrasound and oxygen Pressure will significantly enhance transdermal water transport compared when only one of them is used.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.37-41
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• 2001

Various characteristics of polyethylene oxide (PEO) are useful for drug delivery systems. In this study, PEO was used as a sustained release matrix system containing cefatrizine propyleneglycol (Cefa-PG) which is a new semi-synthetic broad-spectrum and orally active cephalosporin. Five kinds of sustained release matrix tablets were formulated with various content of PEO and other ingredients. And three types of matrix tablets were formulated of which compositions were the same but the hardness was different. It was found that PEO content influenced drug release rate. Increasing PEO content, the drug release rate from matrix tablets was decreased. In addition, Avicel, one of the ingredients of matrix components, changed the drug release from the sustained release PEO matrix tablets. With increasing Avicel content, the rate of drug release was increased. For the effect of hardness of matrix tablets, the rate of drug release is decreased with increasing hardness. In comparison of bioavailability parameters after oral administration of Cefa-PG PEO matrix tablets and general Cefa-PG capsule in beagle dog, the sustained release PEO matrix tablets is more useful than a general dosage form. $AUC^{0-12}$ of the sustained release PEO matrix tablet and the general dosage form was 1.16 and 0.644 respectively.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.127-134
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• 2008

Peroral administration is the most convenient one for the administration of pharmaceutically active compounds. Most of poorly water-soluble drugs administered via the oral route, however, remain poorly available due to their precipitation in the gastrointestinal (GI) tract and low permeability through intestinal mucosa. In this study, one of drug delivery carriers, lipid nanoparticles (LNPs) were designed in order to reduce side effects and improve solubility and stability in GI tract of the poorly water soluble drugs. However, plain LNPs are generally unstable in the GI tract and susceptible to the action of acids, bile salts and enzymes. Accordingly, the surface of LNPs was modified with polyethylene glycol (PEG) for the purpose of improving solubility and GI stability of paclitaxel (PTX) in vitro. PEG-modified LNPs containing PTX was prepared by spontaneous emulsification and solvent evaporation (SESE) method and characterized for mean particle diameter, entrapping efficiency, zeta potential value and in vitro GI stability. Mean particle diameter and zeta potential value of PEG-modified LNP containing PTX showed approximately 86.9 nm and -22.9 mV, respectively. PTX entrapping efficiency was about 70.5% determined by UV/VIS spectrophotometer. Futhermore, change of particle diameter of PTX-loaded PEG-LNPs in simulated GI fluids and bile fluid was evaluated as a criteria of GI stability. Particle diameter of PTX-loaded PEG-LNPs were preserved under 200 nm for 6 hrs in simulated GI fluids and bile fluid at $37^{\circ}C$ when DSPE-mPEG2000 was added to formulation of LNPs above 4 mole ratio. As a result, PEG-modified LNPs improved stability of plain LNPs that would aggregate in simulated GI fluids and bile solution. These results indicate that LNPs modified with biocompatible and nontoxic polymer such as PEG might be useful for enhancement of GI stability of poorly water-soluble drugs and they might affect PTX absorption affirmatively in gastrointestinal mucosa.

• Journal of Pharmaceutical Investigation
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• v.37 no.2
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• pp.101-106
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• 2007

Venlafaxine, 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol hydrochloride is a novel, nontricyclic antidepressant. venlafaxine is a unique antidepressant that differs structurally from other currently available. The aim ot the study was to formulate sustained-release venlafaxine granules and assess their formulation variables. It consists of two layers, venlafaxine drug layer and sustained release coating layer and manufactured by fluidized bed process. The sustained release of drug could be increased by double-control rising various components in venlafaxine drug layer and sustained-release layer. The drug-containing granules were coated with cellulose acetate, cetyl alcohol and Eudragit RS along with plastisizer such as dibuthyl sebacate as an nano-pore former The release oi venlafaxine depended on the type of Eudragit such as RS, and RL used in the formulation of controlled release layer. These results obtained clearly suggest that the sustained release oral delivery system for venlafaxine could be designed with satisfying drug release profile approved.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.751-765
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• 1997

Periodontal disease is a bacterially causal by disease, To remove plaque and bacteria, it has been necessary to prescribe chemical drug to patient to subjugate therapeutic unvalue by mechanical scaling. As a patient on a high dosage of the antibiotics to maintain the effective concentration may produce unfavorable side effects, this decase demands the Slow-release local drug delivery system. The object of the experiment is to study on the slow-release local drug delivery effects of calcium sulfate compounded with tetracycline that mainly used in periodontal disease. Experimental groups were divided into four classes as follow: Group 1 10% tetracycline compounded modified calcium sulfate paste. Group 2 : compounded and hardened 10% tetracycline and calcium sulfate. Group 3 : compounded 10% tetracycline and calcium sulfate, used Just before hardened. Group 4 : tetracycline-ethylene vinyl acetate fiber. In the four groups, release concentration, it's durability and the period of absorption by times are observed and concluded as follow: 1. An effective concentration($4{\mu}g/ml$) remained until 5 weeks in group 1, 9 days in group 2, 7 days in group 3, 15 days in group 4. 2. It was fully fused at 11.8 days average in group 2 and 14.8 days average in group 3. . There were no statistically significant results in tetracycline concentration until a week in group 2 and 3(p<0.05) These results suggest that tetracycline loaded calcium sulfate release sufficient tetracycline and fused in $11{\sim}14$ days, so calcium sulfate is useful carrier as slow release local drug delivery system.

• Applied Chemistry for Engineering
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• v.32 no.5
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• pp.509-515
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• 2021

In this study, poly lactic-co-glycolic acid (PLGA) nanoparticles (PNP) were prepared through double (w/o/w) emlusion and emulsifying solvent-evaporation technique using PLGA, which has biocompatibility and biodegradability. To maximize stability and bioavailability of the particles, chitosan-coated PLGA nanoparticles (CPNP) were prepared by charge interaction between PNP and chitosan. We demonstrated that CPNP can be utilized as a drug carrier of oral administration. The chemical structure of CPNP was analyzed by ¹H-NMR and FT-IR, and all characteristic peaks appeared, confirming that it was successfully prepared. In addition, particle size and zeta potential of CPNP were analyzed using dynamic light scattering (DLS) while morphological images were obtained using transmission electron microscope (TEM). Thermal decomposition behavior of CPNP was observed through thermogravimetric analysis (TGA). In addition, the cytotoxicity of CPNP was confirmed by MTT assay at HEK293 and L929 cell lines, and it was proved that there is no toxicity confirmed by the cell viability of above 70% at all concentrations. These results suggest that the CPNP developed in this study may be used as an oral drug delivery carrier.

• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.167-171
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• 2007

Itraconazole is one of the most potent antifungal agents available in the market today. However, the low bioavailability due to its poor-water solubility calls for an alternative formulation to the current oral type. A topical itra-conazole-containing formulation may be of use for several reasons including the opportunity to reduce adverse events and generate high local tissue levels, more rapid drug delivery, and lower systemic exposure. The purpose of the present study was to investigate the vehicles for topical skin delivery of itraconazole. The effect of formulations on the hairless mouse skin permeation and deposition of itraconazole was determined using Franz diffusion cells at $37^{\circ}C$. Benzyl alcohol in micro-emulsion significantly increased the solubility of itraconazole, thereby increasing the skin permeation rate. However, lipo-some formulation showed the lowest solubility and permeation rate of itraconazole. Although the solubility of itraconazole in hydrogel formulation was lower than that in microemulsion, skin permeation rate was significantly higher probably due to its adhesive property. Therefore, microemulsion-based hydrogel formulation is expected to synergistically increase the skin permeation rate and skin deposition of itraconazole.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.363-369
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• 2006

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.

• The Korean Journal of Pain
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• v.22 no.1
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• pp.68-73
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• 2009

Opioids profoundly inhibit evoked discharges of spinal nociceptive neurons, thereby inhibiting the transmission of pain. Intrathecal administration of opioids using implantable continuous infusion systems is an effective method of pain relief when other treatments have failed, as well as for patients with adequate analgesia on high dose therapy that produces unacceptable side effects. We report two cases of intrathecal pump implantation performed in patients suffering from intractable chronic pain. A test dose of 3 mg morphine was injected into the epidural space. No side effects were noted and patients experienced considerable pain relief. Implantation was performed one day after the test. The initial intrathecal morphine delivery dose was half of the equivalent dose of daily oral intake opioids and the infusion rate was increased gradually under close observation for opioid side effects. Two days post-implantation, both patients were discharged without any complications.