• The Korean Journal of Zoology
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• v.32 no.4
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• pp.329-338
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• 1989

Present study examined the effect of intermittent versus continuous infusion of progesterone(P) on LHRH release in uiuo from the mediobasal hvpothalamus of ovariectomiEed, estradiol-primed adult rats bearing push-pull cannulae. Three experimental groups were studied: 1) control (perfusion medium only),2) intermittent perfusion of P (10-min on,20-min off, and 3) continuous perfusion of p. p (10 ng/mll was directly infused into the MBH following a 3 hr basal collection. Perfusates were collected at 10 min intents린s on ice and LHRH release was measured by LHRH radioimmunoassav. Cycle detector analysis revealed that the spontaneous HRH output in the control group was pulsatile over a 7 hr push-pull perfusion period. The mean basal LHRH release, pulse amplitude and pl서se period were 0.68 $\pm$ 0.03 ps110 min, 1.15 $\pm$0.08 pg and 60 $\pm$ 9 min, respectivelv. Intermi구eat perfusion of P clearly stimulated the mean LHRH release (pre-P vs post-P: 1.14 $\pm$ 0.18 vs 1.99 $\pm$ 0.53 pg) without changes in LHRH pulse frequency. In contrast to intermittent infusion of p, continuous administration of P faithed to modify LHRH release, since the mean LHRH release and pulse amplitude between pre-P and post-P perfusion urere similar. The in vitro study clearly showed that intermittent, but not continuous administration of P is effective in stimulating LHRH release. Therefore, it appears that rhythmic secretion of P mal be the erective signal for activating the neural LHRH apparatus.

• Journal of Pharmaceutical Investigation
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• v.19 no.4
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• pp.179-183
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• 1989

Drug release experiments were performed based on pH-sensitive swelling behaviors of polymethacrylic acid. 5-Fluorouracil as a nonionic model drug revealed release patterns depending solely on pH-dependent swelling kinetics of polymethacrylic acid. In contrast, release of propranolol hydrochloride as a cationic model drug was significantly affected by ionic drug-polymer interaction as well as the swelling kinetics. Accordingly, a zero-order release pattern was obtained at pH 7, which was distinguished from the general matrix type drug release pattern.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.453-460
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• 2005

4-Aminopyridine (AP) is a potassium channel blocker used in the treatment of neurological disorders such as multiple sclerosis and Alzheimer disease. AP‘s window of therapeutic effect appears to correlate with its plasma halflife (3.5 hours). It demonstrates pH-dependent solubility because of a weakly basic drug. In addition, the resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study is to design sustained release matrix tablet containing AP, overcoming this problem. $Eudragit^{\circledR}$ L 100 (EuL) and sodium alginate were used in an effort to achieve pH independent drug release. The effect of sodium alginate and EuL on drug release from matrix tablet was investigated. The drug release behavior from the different tablets was analyzed by $t_{20%},\;t_{40%},\;t_{60%}$, The exponential diffusion coefficient n, kinetic constant K were calculated according to the Korsmeyer-Peppas equation. The drug release from matrix tablets prepared with sodium alginate was decreased with increasing the content of sodium alginate in pH 7.4 while there is no significant difference in pH 1.2. The exponent n values were determined to be approximately 0.5 and 0.8 respectively, in both pH 1.2 and 7.4. These values indicate diffusion-based anomalous mechanism and erosion-based anomalous mechanism, respectively. The drug release from sodium alginate matrix tablets prepared with solid dispersion of EuL containing drug showed a slow drug release in an acidic medium and a more fast drug release in phosphate medium, compared with sodium alginate matrix tablets prepared with physical mixture. These results may be attributed to the gel forming ability of sodium alginate and pH dependent solubility of EuL. Therefore, sustained-release AP matrix tablets using sodium alginate and EuL were successfully prepared.

• KSBB Journal
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• v.10 no.4
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• pp.461-467
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• 1995

In this study, the release experiments of drug were operated in the phosphate buffer solutions of pH 7.4 and pH 1.2 by using drug carriers(chitosan, chitosan hydrochloride, and sulfonated chitosan)coated by poly(DL-lactide) with prednisolone for delivery drug. The release time of drug was more delayed in pH 7.4 than in pH 1.2. The release time of according to the kinds of drug carrier was delayed in the order of chitosan, sulfonated chitosan, and chitosan hydrochloride. In short, the formulation allows biodegradable coated monolithic polymetic matrices to suppress the burst effect of the drug release mechanism, which led to the sustained release pattern.

• KSBB Journal
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• v.11 no.6
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• pp.676-680
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• 1996

The characteristics of controlled drug release were studied for a biodegradable drug delivery system. A biodegradable chitosan matrix was prepared after swelling chitosan with 10%-acetic acid and adding sulfadiazine. The release behavior of sulfadiazine from the chitosan matrix was studied using the Higuchi's diffusion controlled model in phosphate buffer solutions of pH 7.4 and pH 1.2. The drug release time was delayed by increasing the content of sulfadiazine. The drug release at pH 7.4 was more delayed than that at pH 1.2. The reason is that chitosan has greater swelling abilities at low pH than at high pH. The apparent release rate constant(K) increased as the concentration of drug increased. In shoat, the formulation the biodegradable chitosan matrix to suppress the burst effect of drug release mechanism, which led to a sustained release pattern.

• Korean Journal of Veterinary Research
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• v.51 no.1
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• pp.1-6
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• 2011

Sixteen steers were used to investigate the efficacy of the sustained-release implant of bovine somatotropin (bST) in improving growth and feed:gain ratio during 12 weeks. Administration of the 400 mg bST implant resulted in a 16.1% increase in growth rate, and this increase was significant (p<.05). The use of the sustained-release implant did not alter (p>.05) feed intake and feed:gain ratio. Thirty-four cows were used to investigate the efficacy of the sustained-release implant of bST in milk production during 4 weeks. Administration of the 200 mg bST implant resulted in an 8.7% increase in milk production, and this increase was significant (p<.05). Twenty-four barrows were used to investigate the efficacy of the sustained-release implant of porcine somatotropin (pST) in improving growth, feed:gain ratio and backfat thickness during 6 weeks. Administration of the 120 mg pST implant resulted in a 11.4% increase in feed:gain ratio and a 60% decrease in backfat thickness, and these results were significant (p<.05). But the use of the sustained-release implant did not alter (p>.05) growth rate and feed intake.

• Archives of Pharmacal Research
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• v.13 no.4
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• pp.293-297
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• 1990

Sustained release microspheres containing phenylpropanolamine HCI (PPA) were prepared with acrylic polymer (Eudragit RL/RS) sand hydroxypropylmethylcellulose phthalate (HPMCP) using a emulsion-solvent evaporation method. Magnesium strate was used a smoothing agent for preparation of microspheres. The microspheres obtained were very spherical and free-flowing particles. Scanning electron microscopy showed that microspheres have a smooth surface and a sponage-like internal structure. The dissolution rate of PPA from the microspheres was dependent on the pH of dissolution media. PPA showed faster relase in hP 1. 2 solution than in pH 7.4 solution due to the solubility of PPA. Therefore we prepared new microspheres containing 5% (w/v) HPMCP in order to control the release of PPA. The release rate of PPA from these new microspheres was similar in pH 1.2 and pH 7.4 solution.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.552-556
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• 2001

Histamine and arachidonic acid (AA) release was measured using the P2-purinoceptor antaongists, phospholipase $A_2{\;}(PLA_2)$ and cyclooxygenase (COX)/lipoxygenase (LOX) inhibitors to determine whether or not ATP-induced histamine release is associated with arachidonic acid (AA) release in rat peritoneal mast cells. ATP increased histamine release in a dose dependent manner, whereas adenosine did not. PPADS (a selective P2X-purinoceptor antagonist) and suramin (a nonselective P2X,2Y-purinoceptor antagonist) inhibited ATP-induced histamine release in a dose dependent manner. However, RB-2 (a P2Y-purinoceptor antagonist) did not block ATP-induced histamine release. Manoalide and oleyloxyethyl phosphorylcholine (OPC), secretory PLA$_2$ inhibitors, also inhibited ATP-induced histamine release dose-dependently. Both COX inhibitors (ibuprofen and indomethacin) and LOX inhibitors (baicalein and caffeic acid) inhibited ATP-induced histamine in a dose dependent manner. ATP significantly increased [$^3H$]AA release by 54%. PPADS and suramin significantly inhibited ATP-induced [3H]Ph release by 81% and 39%, respectively. ATP-induced histamine release was significantly inhibited by a variety of protein kinase inhibitors, such as bisindolmaleimide, genistein, methyl 2,5-dihydroxycinnamate, W-7 and trifluoperazine. Overall, the results suggest that ATP-induced histamine release is in part related to the PLA2-mediated AA metabolism and P2X-purinoceptors.

• Archives of Pharmacal Research
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• v.12 no.2
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• pp.88-93
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• 1989

In order to obtain some informations about the effect of molecular weight on the release rate of drug from drug carrier, two types of poly-L-glutamic acid (PLGA)-cytarabine (ara-C) conjugates, PLGA-ara-C:I and PLGA-ara-C:II, were synthesized using two types of PLGA having different average molecular weight, 43,000 and 77,800, respectively. The PLGA-ara-C conjugates were synthesized by mixed anhydride method and found to be covalently linked. Both types of conjugates charged negatively at biological pH. The pH-dependent release rate of ara-C was observed in both cases, and the release rate was accelerated in basic, acidic conditions (the k values were 0.015 $day^{-1}$ at pH 7.0, 0.024 $day^{-1}$ at pH 5.0, and 0.059 $day^{-1}$ at pH 9.0 in the case of PLGA-ara-C:I) and in the presence of pretense. The time required for the release of 16.5% of ara-C from PLGA-ara-C:I were 8 hr and 144 hr in the presence and absence of protease, respectively. Although both types of conjugates showed similar drug substitution ratio, they showed different release rates. Between the two types of conjugates, PLGA-ara-C:II showed the faster release rate (0.030 vs 0.042 $day^{-1}$ in pH 7.4 phosphate buffer solution at $37^{\circ}C$) and the smaller activation energy for the release of drug (12.5 vs 7.7 Kcal/mol) than PLGA-ara-C:I. The characteristic effect of molecular weight on the release rates of PLGA-ara-C conjugates suggests that the drug release rate might be effectively controlled over a prolonged period of time by the combined use of the different types of PLGA-ara-C conjugates having different molecular weights.

• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.5
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• pp.326-331
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• 2001

With the aim of developing of pH-sensitive controlled drug release system, a poly(Llysine) (PLL) based cationic semi-interpenetrating polymer network (semi-IPN) has been synthesized. This cationic hydrogel was designed to swell at lower pH and de-swell at higher pH and therefore be applicable for achieving regulated drug release at a specific pH range. In addition to the pH sensitivity, this hydrogel was anticipated to interact with an ionic drug, providing another means to regulate the release rate of ionic drugs. This semi-IPN hydrogel was prepared using a free-radical polymerization method and by crosslinking of the polyethylene glycol (PEG)-methacrylate polymer through the PLL network. The two polymers were penetrated with each other via interpolymer complexation to yield the semi-IPN structures. The PLL hydrogel thus prepared showed dynamic swelling/de-swelling behavior in response to pH change, and such a behavior was influenced by both the concentrations of PLL and PEG-methacrylate. Drug release from this semi-IPN hydrogel was also investigated using a model protein drug, streptokinase. Streptokinase release was found to be dependent on its ionic interaction with the PLL backbones as well as on the swelling of the semi-IPN hydrogel. These results suggest that a PLL semi-IPN hydrogel could potentially be used as a drug delivery platform to modulate drug release by pH-sensitivity and ionic interaction.