• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.303-311
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• 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
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• v.35 no.4
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• pp.273-278
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• 2005

Nicotine transdermal therapeutic systems $(TTS_S)$ have been regarded as an effective mean to aid smoking cessation. However, most of nicotine $TTS_S$ in the market have some problems such as unpleasant side effects and skin irritation due to the excess amount of the drug permeated and the properties of the additives employed. In order to solve these problems, new nicotine $TTS_S$ were formulated using biocompatible additives. The optimized formula of the drug layer consisted of nicotine, propylene glycol and poloxamer 188 at the ratio of 1.2: 17.0: 2.0. The drug layer had the sickness of $1,250\;{\mu}m$, the pH of 8.12. The skin permeation rate of nicotine from optimized nicotine patch (NP) was $21.5\;{\mu}g/cm^2/h$. Transdermal administration of nicotine patch has been carried out for the determination of pharmacokinetic parameters in rats. Steady-state plasma concentration of nicotine following transdermal application of NP (area of patch = $15\;cm^2$) on the dorsal skin of rats was 143.2 ng/ml and AUC for 24 hrs was 3,022 ng h/ml. In case of $EXODUS^{\circledR}$ and Nicotinell $TTS^{\circledR}$, the steady-state plasma concentration of nicotine and ACU for 24 hrs were 428.9 ng/ml, $9,121\;ng{\cdot}hr/ml$ and 155.3 ng/ml, $3,152\;ng{\cdot}h/ml$, respectively. NP showed the experimental plasma nicotine concentration profile was very similar to the simulated one and had an appropriate skin permeation rate and a steady-state concentration of nicotine, which can show therapeutic blood levels of the drug for 24 hrs without severe side effects.

• Journal of mucopolysaccharidosis and rare diseases
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• v.1 no.1
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• pp.5-14
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• 2015

This paper addresses the state of arts of microneedles for the transdermal drug delivery applications. Microneedles can be classified based on materials and shapes. For the materials, microneedles could be made of ceramics, metals and polymers. The shape of the microneedles can be classified into solid and hollow microneedles. Methods of transdermal drug delivery based on microneedle patch are discussed, and various fabrication methods of microneedle patches are introduced.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2010.05a
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• pp.1435-1436
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• 2010

• YAKHAK HOEJI
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• v.43 no.4
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• pp.447-457
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• 1999

The purpose of this study is to prepare the adhesive type patch containing flurbiprofen, and to demonstrate the feasibility of flurbiprofen administration through the intact skin using adhesive type patch preparation. For this purpose, two pressure sensitive adhesives, Polyisobutylene(PIB) and $Gelva^{\circledR}737$, were selected from the chemical grade of polymers, and the adhesive type patches of flurbiprofen were prepared. The release rate of flurbiprofen from the PIB-based adhesive patch was higher than that from $Gelva^{\circledR}737$ based adhesive patch. The release rate of flurbiprofen from the PIB-based A-type patch with 1.0mm, 1.5mm or 2.0mm thicknesses followed the first order kinetics. In the skin permeation study, using male hairless mouse skin, a monophasic skin permeation profile was observed with 1% flurbiprofen loading dose. The inclusion of palmitic acid or SLS(0.25~0.5%) as an enhancer produced a remarkable enhancement in the skin permeation rate of flurbiprofen, and the percentile ratio of drug and enhancer appeared to be important for the effective enhancement. In the in vivo percutaneous absorption study, the plasma concentration of the optimal formulation was significantly (p<0.01) higher than that of the conventional cataplasma ($Bifen^{\circledR}$). These studies demonstrate a good feasibility of flurbiprofen administration through the intact skin using a transdermal patch, and show a possibility of the development of flurbiprofen patches.

• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.97-102
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• 2006

The aim of this study was to investigate the feasibility and optimize permeability of slim patch type as a transdermal delivery system of caffein. Slim patch type was formulated and tested in modified Franz diffusion cell across cellulose membrane and hairless mouse skin in pH 5.8 phosphate buffer solution (PBS). The effect of $Pharmsolv^{\circledR}$ and drug concentration on permeation at four model, 1,2% $Pharmsolv^{\circledR}$ with $0.12\;mg/cm^2$ caffein and 0.12, $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ through hairless mouse skin was studied in vitro. The release of caffein from slim patch with various loading was fitted by the Higuchi's diffusion equation. The result showed that chemical $Pharmsolv^{\circledR}$ produced a large and significant increase of permeation. The effect of 2% $Pharmsolv^{\circledR}$ on permeation of caffein was greater about 10-fold greater than 1% $Pharmsolv^{\circledR}$ in first 60 minutes. The effect of drug concentration, however, was lower than that produced by chemical $Pharmsolv^{\circledR}$. Within the tested system, the most efficient combination for caffein slim patch type was $0.12\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR},$ although $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ showed highest amounts permeation, because permeated percentages were significantly lower about $1/4{\sim}1/5$ times.

• Polymer(Korea)
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• v.33 no.3
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• pp.237-242
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• 2009

This study examined the transdermal delivery of alendronate across hairless mouse skin. The effects of iontophoresis, perforation with a microneedle, and a combination of a microneedle pretreatment and iontophoresis were evaluated in vitro test. Hydrogel patches were polymerized by UN polymerization to supply a hydrogel patch to the iontophoretic transdermal drug delivery system. The alendronate content in the iontophoretic delivery patch was $5.0\;mg/cm^3$. The amounts of alendronate that permeated across the hairless mouse skin when current densities of 0.25 and $0.50\;mA/cm^2$ were supplied to the iontophoretic alendronate patch were $0.80{\pm}0.03$ and $2.00{\pm}0.02{\mu}g$, respectively. After pretreatment with a microneedle, the amounts of alendronate that permeated across the hairless mouse skin increased to $70.65{\pm}0.37$ and $162.23{\pm}0.40{\mu}g$, respectively. The biocompatibility of the iontophoretic alendronate patch was examined according to the international standardization organization 10993.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.247-252
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• 2000

The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease. For the development of transdermal systems containing clenbuterol, two limiting factors - long lag time and low flux - must be overcome. In this study, we attempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of clenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Furthermore, the clenbuterol patch composed of 15% clenbuterol, 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levels in in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.

• YAKHAK HOEJI
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• v.34 no.3
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• pp.161-165
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• 1990

An automated, simple, and reliable method was developed for determining in vitro drug release rate from transdermal delivery dosage forms. The patch is held in position in the heating block by sandwiching it between the middle plate and the bottom plate of diffusion cell. The dissolution profile of the commercially available transdermal scopolamine patch was determined over a 72-h period, and the results were compared with those obtained with other methods; paddle-over-disk method, reciprocating method, and diffusion cell method. It was demonstrated that the flow-through method is equivalent in terms of release rate profile and accumulated released drug amount over the lifetime of the dosage form tested. Also this method is simple, reliable and reproducible. Therefore, this technique can be used in a quality control for assuring product uniformity.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.70-74
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• 1999

Background: Preemptive analgesia has been suggested recently as an another technique of postoperative pain control. Combination of low dose opioid and NSAIDs was used to lessen systemic opioid side effect, however, the use of NSAIDs may hinder their side effects in perioperative period. The local application of small dose at the target site can be effective without systemic effect. The aim of this study is evaluating the additive effect and side effect of transdermal piroxicam as preemptive adjuvant to intravenous nalbuphine on pain relief after major abdominal surgery. Methods: We reviewed the records of patients received piroxicam patch for preemptive analgesia before operation and compared it with control group. Two sheets of piroxicam patch to the skin incision site for 12 hours before operation were attached (Group 1, n=20) and no patch were applied (Group 2, n=20). Both groups were received nalbuphine continuously after operation using two days infuser (2 ml/hr) containing 80 mg (96 ml). Pain is evaluated by VAS score at each time; 30 min, 1, 6, 12, 24, 36, 48 hours after operation and side effects of NSAIDs were observed for 3days postoperatively. Results: There was no significant VAS score difference between two groups following time in progress. And no significant side effect was noted in both groups, either. Conclusion: There is no preemptive or synergistic analgesic effect of piroxicam patch attached at planned operation site before operation.