• Journal of Pharmaceutical Investigation
• /
• 제30권1호
• /
• pp.27-32
• /
• 2000

Various release test methods have been applied for the evaluation of nicotine release in vitro from commercial patches. However, whether and how the release data reflect the permeation of nicotine across the skin, is not fully elucidated. To predict in vivo bioavailability from in vitro release tests, correlation between in vitro release and in vitro skin permeation was assessed in the present study. Release of nicotine from three commercial patches was measured for 24 hours under nine experimental conditions which were classified depending on the apparatus (i.e., paddle over disk, cylinder and reciprocating holder) and dissolution media (i.e., phosphate buffer pH 7.4, water and the 1 % phosphoric acid pH 1.5). In vitro permeation of nicotine from the patches across the human cadaver skin was also measured using a diffusion cell. The release of nicotine was better explained by the Higuchi's equation rather than by the first order rate equation. Correlation between the release rate and the in vitro skin permeation differed among the patches. However, in general, the cylinder method, in which water is used as a dissolution medium, showed the highest correlation among the nine release test conditions.

• 한국임상약학회지
• /
• 제1권1호
• /
• pp.23-30
• /
• 1991

The sustained-release beads containing terbutaline sulfate (TBS) were prepared by rotogranulation method. The drug was dusted on the non-pareil seeds in a CF-granulator. The sustained-release beads were obtained by coating the active beads with ethylcellulose or $Eudragits^{(R)}$, using in any case the same granulator employed for active beads preparation. The release characteristics of sustained-release beads were examined in vitro by rotating basket method applied to $Bricanyl^{(R)}$ durules which is a sustained-release TBS matrix tablet. The release of terbutaline from the beads in vitro was first-order, and the release rate was dependent on both the coat weight ratio and membrane hydrophilicity. Both surfaces of the beads before and after dissolution were smooth. The drug release pattern from the beads could be thought the diffusion through the polymer membrane. The release rate and the surface of the beads stored for 3 years at room temperature were the same with those of the initial beads.

• Journal of Pharmaceutical Investigation
• /
• 제28권4호
• /
• pp.275-282
• /
• 1998

In order to develop a desirable in vitro release which correlates well with in vivo bioavailability, hollow type suppository containing Propranolol HCl(PPH) powder in the cavity and conventional type suppository with dispersed PPH in the base were prepared. Polyvinyl alcohol (PVA) hydrogel as a base and PPH as a model drug were used for the preparation of suppository. The rates of drug release from the suppositories were studied by Paddle method, Muranish method, Dialysis tubing method and Rotating dialysis cell method. The release profiles from suppositories using the four different release tests were compared. After a rectal administration in rat, the mean $C_{max}$ of hollow type suppository was significantly lower than that of conventional type, but $T_{max}$, $AUC_{0{\to}12}$ and MRT of hollow type were significantly higher 1.6 times, 1.2 times and 1.9 times than those of conventional type, respectively. The computer program was used to simulate plasma concentration from in vitro released amounts of drug and in vivo pharmacokinetic parameters. Based on comparison of the simulated bioavailability from computer program with experimental bioavailability in rat we have found out in vitro release test which correlates well with in vivo bioavailability. Our results have shown the best correlation between in vitro release and in vivo bioavailability in PPH-PVA hydrogel hollow type suppository for the paddle method and conventional type suppository for the rotating dialysis cell method. In this work we propose that PPH-PVA hydrogel suppository shows in vitro-in vivo correlation. This data should help to optimize the formulation of the drug and provide a basis for quality control procedures.

• The Korean Journal of Physiology
• /
• 제29권1호
• /
• pp.1-11
• /
• 1995

Alveolar macrophages play a pivotal role in the pathogenesis of silicosis since the macrophages may release a wide variety of toxic and inflammatory mediators as well as mitogenic growth factors. In the present study, the effects of in vitro exposure to silica on release of various mediator such as reactive oxygen species, platelet activating factor(PAF), and interleukin-1 (IL-1) by alveolar macrophages were examined. First, hydrogen peroxide release from alveolar macrophages was monitored by measuring the change in fluorescence of scopoletin in the absence or presence of graded concentration of silica. Significantly enhanced release of hydrogen peroxide was observed at 0.5 mg/ml and above. A maximal enhancement of 10 fold above control was observed at 5 mg/ml silica. Similarly, in vitro exposure to silica also significantly stimulated the generation of chemiluminescence from alveolar macrophages at 0.5 mg/ml and above with n maximal enhancement of 8 fold at 5 mg/ml silica. Second, PAF release from alveolar macrophages after 30 min incubation at $37^{\circ}C$ in absence or presence of zymosan and silica was determined by measuring $^{3}H-serotonin$ release ability of the conditioned macrophage supernates from platelets. 5 mg/ml zymosan as a positive control fur the PAF assay increased PAF release by 19 % of total serotonin release. Furthermore, silica also resulted in significant enhancement of the PAF release compared with that in unstimulated (control) cells, i.e., $17.7{\pm}5.8%$ and $24.0{\pm}4.9%$ of total serotonin release at 5 mg/ml and 10 mg/ml silica, respectively, which represents the release of nanomole levels of PAF. Lastly, IL-1 production by alveolar macrophages was analysed following their stimulation with lipopolysaccharide (LPS) and silica by their capacity to stimulate thymocyte proliferation. $10\;{\mu}g/ml$ LPS resulted in an 11 fold increase in IL-1 production. In comparison, $50\;{\mu}g/ml$ silica resulted in a 4 fold increase in IL-1 release. These data indicate that in vitro exposure of alveolar macrophages to silica activates the release of various bioactive mediators such as reactive oxygen species, PAF and IL-1 which thus contribute to amplification of inflammatory reactions and regulation of fibrotic responses by the lung after inhalation of silica.

• Asian-Australasian Journal of Animal Sciences
• /
• 제12권7호
• /
• pp.1031-1034
• /
• 1999

Circulating lymphocytes collected from control and heat-stressed buffaloes were subjected to in vitro culture with glucocorticoids, epinephrine or serotonin and their effect, if any, on the release of intracellular prolactin (PRL) was studied using ELISA and C-ELISA techniques. It was noted from the study that PRL level was higher in lymphocytes than in plasma of the control and heat-stressed animals, and that the PRL levels increased in the plasma of heat-stressed animals compared to that of non stressed animals with a significant decrease in lymphocytic PRL content by heat stress. Epinephrine and serotonin significantly increased the release of intracellular PRL from the lymphocytes of both in the control and the heat-stressed buffaloes but release of PRL from lymphocyte was not significantly changed by cortisol treatment in both control and heat-stressed buffaloes as compared to epinephrine and serotonin in vitro. When lympocytes were incubated with serotonin, it caused drastic lysis of the lymphocytes but epinephirine and cortisol did not show any lysis. It may be concluded from this study that hormones like epinephrine or serotonin known to increase during stress, release intracellular PRL from lymphocytes, the satellite PRL storage/synthesizing organ of blood, although the mechanism of the release is different.

• Archives of Pharmacal Research
• /
• 제28권9호
• /
• pp.1092-1096
• /
• 2005

Huperzine A-loaded microspheres composed of poly(D,L-lactide-co-glycolide) were prepared by an O/w emulsion solvent evaporation method. The characterization of the microspheres such as drug loading, size, shape and release profile was described. The in vitro release in the initial 7 days was nearly linear with $10\%$ released per day. Thereafter drug release rate became slow gradually and about $90\%$ drug released at day 21. The in vitro release rate determined by dialysis bag method had a good correlation with the in vivo release rate. Huperzine A aqueous solution was intramuscularly injected (i.m.) at 0.4mg/kg and microspheres were intra­muscularly injected at 8.4 mg eq huperzine A/kg in rats. The maxium plasma concentration $(C_{max})$ after i.m. microspheres was only $32\%$ of that after i.m. solution. Drug in plasma could be detectd until day 14 and about $5\%$ of administered dose was residued at the injection site at day 14. The relative bioavailability of huperzine A microspheres over a period of 14 days was $94.7\%$. Inhibition of acyecholinesterase activity (AchE) in rat's cortex, hippocampus and striatum could sustain for about 14 days. In conclusion, huperzine A-loaded microspheres possessed a prolonged and complete drug release with significant inhibition of AchE for 2 weeks in rats.

• Journal of Pharmaceutical Investigation
• /
• 제32권4호
• /
• pp.321-325
• /
• 2002

IVIVC (In vitro/in vivo correlation) is useful for predicting in vivo results from in vitro data. The aim of this study was to develop IVIVC of sustained release diltiazem. For this purpose, three types of diltiazem tablets with different in vitro dissolution rates were prepared. An in vitro dissolution testing method comprising of paddle apparatus, 50 rpm, water as dissolution medium was developed. Under these condition, we demonstrated that AUCinf could be predicted by evaluating $d_{70%}$ (time dissolved 70%) in vitro since the in vivo AUCinf was correlated with the in vitro $d_{70%}$ (r=-0.9981).

• 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
• /
• 제19권4호
• /
• pp.195-202
• /
• 1989

In attempt to improve the chemotherapeutic activity of adriamycin, adriamycin-entrapped HSA microspheres were prepared and investigated by the various in vitro experiments. The shape, surface characteristics and size distribution of HSA microspheres are observed by scanning electron microscopy. The in vitro drug release, albumin matrix degradation by protease of HSA microspheres were studied. The shape of HSA microspheres were spherical and the surface was smooth and compact. The size of HSA microspheres ranged from 0.4 to $2.5\;{\mu}m$ and have average diameters of 0.5 to $0.7\;{\mu}m$. The size distribution of HSA microspheres prepared by ultrasonication was mainly affected by albumin concentration and heating time in the process of hardening. In in vitro, almost all adriamycin was released from HSA microspheres for 8 hr. Analysis of the resulting adriamycin release profiles demonstrated that adriamycin is released from the microspheres in two distinct steps, a fast phase (until 30 min) followed by a much slower sustained release phase. Drug release, which is due to diffusion, was depended on the rate of matrix hydration. Drug release was largely affected by albumin concentration and heating temperature during the process of hardening. Albumin matrix degradation of HSA microspheres was affected by heating temperature and albumin concentration. Higher temperature and longer times generally produce harder, less porous, and slowly degradable microspheres.

• Journal of Pharmaceutical Investigation
• /
• 제26권1호
• /
• pp.13-22
• /
• 1996

Poly(D,L-lactic acid) (PLA) microspheres containing alprazolam(APZ) were prepared by a solvent-emulsion evaporation method and their release patterns were investigated in vitro. Various batches of microspheres with different size and drug content were obtained by changing the ratio of APZ to PLA, PLA concentration in the dispersed phase and stirring rate. Rod-like APZ crystals on microsphere surface, which were released rapidly and could act as a loading dose, were observed with increasing drug content. The release rate was increased with increase in drug contents and decrease in the molecular weight of PLA. The release rate of APZ for long-acting injectable delivery system in vitro, which would aid in predicting in vitro release profile, could be controlled by properly optimizing various factors affecting characteristics of microspheres.