• Journal of Pharmaceutical Investigation
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• v.29 no.3
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• pp.185-191
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• 1999

The polymeric films containing drug and various excipients were fabricated using aqueous-based $Eudragit^{\circledR}$ RS 30D dispersions. The diffusional behaviors and mechanism of the fabricated polymeric film were investigated using Keshary-Chien diffusion cell. The melatonin was used as a model drug. The diffusion behaviors of drug through the fabricated polymeric films were highly dependent on drug concentration in donor part, polymer contents and drug concentration, and the types of plasticizers and solubilizers. The fabricated polymeric films containing excipients and solubilizers could be applied for the controlled release of poorly water-soluble drug and for the preparation of drug-containing latex films for topical or oral drug delivery.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.19-25
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• 2001

The purpose of this study was to use a ternary polymeric matrix system for high drug loading of a highly soluble drug for controlled release delivery. The controlled drug delivery of diltiazem HCl (solubility > 50% in water at $25^{\circ}C$) with high loading dose (the final loading dose of drug was 34%) from a ternary polymeric matrix (gelatin, pectin, HPMC) was successfully accomplished. This simple monolithic system with 240 mg drug loading provided near zero-order release over a 24 hour-period by which time the system was completely dissolved. The release kinetics of diltiazem HCl tablet with high loading dose from the designed ternary polymeric system was dependent on the ratios of HPMC : pectin binary mixture. The release rate increased as pectin : HPMC ratio were increased. Swelling behavior of the ternary system and the ionic interaction of formulation components with cationic diltiazem molecule appear to control drug diffusion and the release kinetics. Comparable release profiles between commercial product and the designed system were obtained. The binding study between gelatin with diltiazem HCl showed the presence of two binding sites for drug interaction with subsequent controlled diffusion upon swelling. This designed delivery system is easy to manufacture and drug release behavior is highly reproducible and offers advantages over the existing commercial product.

• Archives of Pharmacal Research
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• v.9 no.2
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• pp.63-73
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• 1986

The use of biodegradable polymetric materials as drug carriers is a relatively new dimension in polymeric drug delivery systems. A number of biodegradable or bioerodible polymers, such as poly(lactic/glycolic acid) copolymer, poly($\alpha$-amino acid), polyanhydride, and poly (ortho ester) are currently being investigated for this purpose. These polymers are useful for matrix and reservoir-type delivery devices. In addition, when chemical functional groups are introduced to the biodegradable polymer backdone, such as poly (N-(2-hydroxypropyl) methacrylamide), the therapeutic agent can be covalently bound directly or via spacer to the backbone polymer. These polymer/drug conjugates represent another new dimension in biodegradable polymeric drug delivery systems. In addition, examples of biodegradable polymeric durg delivery systems currently being investigated will be discussed for the purpose of demonstrarting the potential importance of this new field.

• KSBB Journal
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• v.14 no.3
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• pp.297-302
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• 1999

The polymeric matrices coated with poly(DL-lactide) were prepared using chitosan derivatives such as chitosan, chitosan hydrochloride, and sulfonated chitosan for application of drug delivery systems. The drug release study using prednisolone as a model drug was performed in the hydrochloride solution at pH 1.2. The release rate of drug was decreased according to the increased content of matrices. The release rate of prednisolone according to the kinds of polymeric matrices coated were decreased in the order to chitosan, sulfonated chitosan, and chitosan hydrochloride. Drug release rate of polymeric matrices coated with poly(DL-lactide) was not only two times slower than noncoated one, but also the burst effect of initial period of drug release was decreased in comparison with noncoated one. From these results, it was expected that these formulations based on the chitosan derivative matrices coasted with poly(DL-lactide) were acceptable drug delivery devices for a sustained-release dosage form of drug.

• Journal of Pharmaceutical Investigation
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• v.23 no.1
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• pp.19-26
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• 1993

The purpose of this paper is to explore the possible applicability of alginate beads as an oral controlled release system of polymeric drugs. Cellulase was used as a model polymeric drug. The release of cellulase from alginate beads was moderately affected by the ratio of cellulase to sodium alginate and strongly affected by $CaCl_2$ concentration. However, the release was not particularly affected by the other factors such as sodium alginate concentration and curing time. The drug was not released from alginate beads at pH 1.2, but was released continuously up to 8 hr at pH 6.8. At pH 6.8, the beads were swollen highly up to 3 hr, thereafter, were eroded into the bulk solution up to 6 hr, completely. Drug release from the beads can be caused due to diffusion and erosion of the matrix. Activity of cellulase was reduced when alginate beads containing cellulase were stored in simulated gastric juice. Further investigation would be necessary to improve the acid resistance of the beads. Since the release of cellulase as a model polymeric drug could be controlled by the regulation of the preparation conditions of alginate beads, the alginate beads may be used for a potential oral controlled release system of such polymeric drugs as polypeptide drugs.

• Macromolecular Research
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• v.12 no.1
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• pp.71-77
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• 2004

We have synthesized various types of poly(ethylene glycol) (PEG)-ibuprofen conjugates by nucleophilic substitution of bromo-terminated PEG with ibuprofen-Cs salt. The conversion of the terminal hydroxyl groups to bromo-termini was quantitative, as was the drug conjugation process, which suggests that the present synthetic method is very useful for the preparation of PEG-based prodrugs from pharmaceuticals having carboxyl functionalities. The drug-release behavior of the prodrugs was examined in both phosphate buffer (PBS, pH 7.4) and rat plasma. From the drug-release behavior in PBS, we determined that each prodrug has high storage stability. The drug-release rate was observed to be much faster in rat plasma than in buffer solution as a result of the acceleration effect provided by enzymes present in the plasma. The drug-release rate in rat plasma depends on the degree of molecular aggregation of the prodrugs, which can be changed effectively by the nature of their spacer groups or by the use of Pluronic as the polymer carrier.

• Macromolecular Research
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• v.16 no.5
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• pp.418-423
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• 2008

Poly[(R)-3-hydroxy butyrate] (PHB) and methoxy poly(ethylene glycol) (mPEG) were conjugated by the transesterification reaction with tin(II)-ethylhexanoate (Sn(Oct)-II) as a catalyst. Hydrophobic PHB and hydrophilic mPEG formed an amphiphilic block copolymer which was formed with the self-assembled polymeric micelle in aqueous solution. In this study, we tried to determine the optimum ratio of hydrophobic/hydrophilic segments for controlled drug delivery. The particle size and shape of the polymeric micelle were measured by atomic force microscopy (AFM) and transmission electron microscopy (TEM). Their size were 61-102 nm with various block ratios. Griseofulvin was loaded in the polymeric micelle as a hydrophobic model drug. The loading efficiency and release profile were measured by high performance liquid chromatography (HPLC). The model drug in our system was constantly released for 48 h.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.173-181
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• 2003

A polymeric micelle drug delivery system was developed to enhance the solubility of poorly-water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The block copolymers consisting of poly(D,L-lactide) (PLA) as the hydrophobic segment and methoxy poly(ethylene glycol) (mPEG) as the hydrophilic segment were synthesized and characterized by NMR, DSC and MALDI-TOF mass spectroscopy. The size of the polymeric micelles measured by dynamic light scattering showed a narrow monodisperse size distribution with the average diameter less than 50 nm. The MW of mPEG-PLA, 3000 (MW of mPEG, 2 K; MW of PLA, 1K), and the presence of hydrophilic and hydrophobic segments on the polymeric micelles were confirmed by MALDI-TOF mass spectroscopy and NMR, respectively. Polymeric micelle solutions of DDB were prepared by three different methods, i.e. the matrix method, emulsion method and dialysis method. In the matrix method, DDB solubility was reached to 13.29 mg/mL. The mPEG-PLA 2K-1K micelle system was compared with the poloxamer 407 micelle system for their critical micelle concentration, micelle size, solubilizing capacity, stability in dilution and physical state. DDB loaded-polymeric micelles prepared by the matrix method showed a significantly increased aqueous solubility (＞5000 fold over intrinsic solubility) and were found to be superior to the poloxamer 407 micelles as a drug carrier.

• Bulletin of the Korean Chemical Society
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• v.33 no.10
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• pp.3208-3212
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• 2012

Controlled drug delivery systems employing microparticles offer lots of advantages over conventional drug dosage formulations. Microencapsulation technique have been conducted with biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) for its adjustable biodegradability and biocompatibility. In this study, we evaluated two techniques, oil-in-water (o/w) emulsion solvent evaporation and spray drying, for preparation of polymeric microparticles encapsulating a newly synthesized drug, SS-AG20, for the long-term drug delivery of this low-molecular-weight drug with a very short half-life. Drug-loaded microparticles prepared by the solvent evaporation method showed a smoother morphology; however, relatively poor encapsulation efficiency and drastic initial burst were discovered as drawbacks. Spray-dried drug-loaded microparticles had an imperfect surface with pores and distorted portions so that its initial burst was critical (70.05-87.16%) when the preparation was carried out with a 5% polymeric solution. By increasing the concentration of the polymer, the morphology was refined and undesirable initial burst was circumvented (burst was reduced to 35.93-74.85%) while retaining high encapsulation efficiency. Moreover, by encapsulating the drug with various biodegradable polymers using the spray drying method, gradual and sustained drug release, for up to 2 weeks, was achieved.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.183-188
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• 1995

Polymeric reinforcement and coatings of alginate beads were carried out to control the release rate of drug from alginate beads. A poorly water-soluble ibuprofen (IPF) was selected as a model drug. A commercially available $Eudragit^{\circledR}$ RS100 was also used as a polymer. Effects of polymeric contents, the presence of plasticizers and amount of drug loading on the release rate of drug were investigated. The release rate of drug from alginate beads in the simulated gastric fluid did not occur within 2 h but released immediately when dissolution media were switched to the simulated intestinal fluid. No significant difference of release rate from polymer-reinforced alginate bead without plasticizers was observed when compared to plain (simple) beads. However, the release rate of drug from polymer-reinforced alginate beads was further sustained and retarded when aluminium tristearate (AT) as a plasticizer was added to polymer. However, polyethylene glycol 400 (PEG400) did not change the release rate of drug from alginate beads although PEG400 was used to improve dispersion of polymer and sodium alginate, and plasticize $Eudragit^{\circledR}$ RS100 polymer. The presence of plasticizer was crucial to reinforce alginate gel matrices using a polymer. As the amount of drug loading increased, the release rate of drug increased as a result of decreasing effects of polymer contents in matrices. The significantly sustained release of drug from polymer-coated alginate beads occurred as the amount of polymer increased because the thickness of coated membrane increased so that cracks and pores of the outer surface of alginate beads could be reduced. The sustained and retarded action of polymer-reinforced and coated beads may result from the disturbance of swelling and erosion (disintegration) of alginate beads. From these findings, polymeric-reinforcement and coatings of alginate gel beads can provide an advanced delivery system by retarding the release rate of various drugs.