• 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.

• 한국생물공학회:학술대회논문집
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• 2000.11a
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• pp.759-760
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• 2000

5-fluorouracil loaded chitosan-cellulose microspheres was prepared by W/O/W multiple emulsions solvent evaporation technique which is appropriate to oral drug delivery. The influences of process parameters on the physical characteristics of microspheres and on in vitro drug release were investigated.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.103-109
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• 2011

The objective of the study was to prepare self-microeulsifying drug delivery system (SMEDDS) incorporating atorvastatin calcium and evaluate its properties and oral bioavailability. Solubility of atorvastatin in various vehicles was determined. Pseudo-ternary phase diagrams were constructed to identify the good self-emulsification region. The droplet size distributions of the resultant emulsions were determined by dynamic light scattering measurement. The mean droplet size of chosen formulation (20% ethyl oleate, 40% tween-80, 40% Carbitol$^{(R)}$) was $23.4{\pm}1.3$ nm. The SMEDDS incorporating atorvastatin calcium appeared to be associated with better performance in dissolution and pharmacokinetic studies, compared with raw atorvastatin calcium. In dissolution test, the release percentage of atorvastatin from SMEDDS mixture could rapidly reach more than 95% within 3 min. Oral $AUC_{0{\rightarrow}8hr}$ values in SD rats was $1994{\pm}335\;ng{\cdot}hr/mL$, which significantly increased (P<0.05) compared with raw atorvastatin calcium. The SMEDDS formulation was relatively stable when stored at $4^{\circ}C$ during 3 months. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin, by the oral route.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.3
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• pp.209-215
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• 2006

Preoperative neoadjuvant chemotherapy using cisplatin and 5-FU is generally given in oral and maxillofacial cancer. At tissue level both inflammation and fibrosis occur after chemotherapy. The cellular changes mimic those of a granulating wound, with activated macrophages and fibroblasts replacing the malignant cells as they are erradicated. Stromal cells, together with extracellular matrix components, provide the microenvironment that is pivotal for tumor cell growth, invasion, and metastatic progression. Vascular endothelial growth factor(VEGF), an important regulator of angiogenesis in cancer, induces mitogenesis of vascular endothelial cells, and vascular permeabilization and microvessel formation in a tumor are associated with tumor nutrition and oxygenation. Also, they are associated with chemotherapeutic drug delivery. Oxygen delivery to tumor appears to rely on a network of microvessels, On the other hand, the tumor microvessel is clearly an important factor in chemotherapeutic drug delivery to cancer cells, and the efficacy of drug delivery can be high in richly vascularized tumors. So, this study was conducted to evaluate the effect of neoadjuvant chemotherapy on microvessel density from 11 patients with tongue cancers. Our results showed that neoadjuvant chemotherapy was seemed to decrease VEGF expression in tumor cells, however, it did not significantly alter VEGF expression in tumor-associated macrophages. Also, Neoadjuvant chemotherapy had little effect on the microvessel density using CD34, and tumor-associated macrophage level using CD68. Thus, tumorassociated macrophages seem to be the key factor associated with the maintenance of microvessel density after neoadjuvant chemotherapy in tongue cancer.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.263-272
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• 2011

Tablet dosage forms have been preferred over other formulations for the oral drug administration due to their low manufacturing costs and ease of administrations, especially controlled-release applications. Controlled-release tablets are oral dosage forms from which the active pharmaceutical ingredient (API) is released over an intended or extended period of time upon ingestion. This may allow a decrease in the dosing frequency and a reduction in peak plasma concentrations and hence improves patient compliance while reducing the risk of undesirable side effects. Conventional singlelayered matrix tablets have been extensively utilized to deliver APIs into the body. However, these conventional single-layered matrix tablets present suboptimal delivery properties, such as non-linear drug delivery profiles which may cause higher side effects. Recently, a multi-layered technology has been developed to overcome or eliminate the limitations of the singlelayered tablet with more flexibility. This technology can give a good opportunity in formulating new products and help pharmaceutical companies enhancing their life cycle management. In this review, a brief overview on the multi-layered tablets is given focusing on the various tablet designs, manufacturing issues and drug release profiles.

• Transactions of the KSME C: Technology and Education
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• v.2 no.2
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• pp.73-80
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• 2014

Drug delivery in human upper airway was studied by the numerical simulation of oral airflow. We created an anatomically accurate upper airway model from CT scan data by using a medical image processing software (Mimics). The upper airway was composed of oral cavity, pharynx, larynx, trachea, and second generations of branches. Thin sliced CT data and meticulous refinement of model surface under the ENT doctor's advice provided more sophisticated nasal cavity models. With this 3D upper airway models, numerical simulation was conducted by ANSYS/FLUENT. The steady inspiratory airflows in that model was solved numerically for the case of flow rate of 250 mL/s with drug-laden spray(Q= 20, 40, 60 mL/s). Optimal parameters for mechanical drug aerosol targeting of predetermined areas was to be computed, for a given representative upper airways. From numerical flow visualization results, as flow-rate of drug-laden spray increases, the drag spray residue in oral cavity was increased and the distribution of drug spray in trachea and branches became more homogeneous.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.234-237
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• 2015

In this study, we developed lysosome-alginate beads for application as an oral drug delivery system (ODDS). The beads harboring lysosomes, which have antimicrobial activity, and various concentrations of alginate were characterized and optimized. For application as an ODDS, pH-dependent lysosome-alginate beads were generated, and the level of lysosome release was investigated by using antimicrobial tests. At low pH, lysosomes were not released from the lysosome-alginate beads; however, at neutral pH, similar to the pH in the intestine, lysosome release was confirmed, as determined by a high antimicrobial activity. This study shows the potential of such an ODDS for the in vivo treatment of infection with pathogens.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.988-994
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• 2005

The purpose of the present study was to prepare multivesicular liposomes with a high drug loading capacity and to investigate its potential applicability in the oral delivery of a peptide, human epidermal growth factor (rhEGF). The multivesicular liposomes containing rhEGF was prepared by a two-step water-in-oil-in-water double emulsification process. The loading efficiency was increased as rhEGF concentration increased from 1 to 5mg/mL, reaching approximately $60\%$ at 5 mg/mL. Approximately $47\%$ and $35\%$ of rhEGF was released from the multivesicular liposomes within 6 h in simulated intra-gastric fluid (pH 1.2) and intra-intestinal fluid (pH 7.4), respectively. rhEGF-loaded multivesicular liposomes markedly suppressed the enzymatic degradation of the peptide in an incubation with the Caco-2 cell homogenate. However, the transport of rhEGF from the multivesicular liposomes to the basolateral side of Caco­2 cells was two times lower than that of the rhEGF in aqueous solution. The gastric ulcer healing effect of rhEGF-loaded multivesicular liposomes was significantly enhanced compared with that of rhEGF in aqueous solution; the healing effect of the liposomes was comparable to that of the cimetidine in rats. Collectively, these results indicate that rhEGF-loaded multivesicular liposomes may be used as a new strategy for the development of an oral delivery system in the treatment of peptic ulcer diseases.

• Journal of Pharmaceutical Investigation
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• v.20 no.1
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• pp.29-33
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• 1990

Plasma and saliva concentrations of acetaminophen (AAP) were determined at various time points by HPLC after oral administration of AAP tablets (AAP 500 mg) to four healthy male Korean subjects. Saliva concentrations (S) of AAP were significantly correlated with plasma AAP concentrations (P). The S/P ratio of AAP was calculated to be 1.05 (r =0.944, $p<10^{-6}$) for all the data points from the subjects. It showed a little intersubject variation and ranged from 0.89 to 1.46 in each subject. Bioavailability parameters such as AUC, $C_{max}$ and $T_{max}$ which are usually obtained from the plasma concentration data will be predictable approximately by saliva concentration data. Saliva seems to be very convinient and useful samples for the preliminary studies of bioavailability and bioequivalence of AAP preparations, since it can be collected frequently without any painful venipuncture to the subjects, that is inevitable in plasma sampling. Evaluation of the bioavailability of a preparation by saliva samples will reduce the cost, time and safety risk greatly in developing a new drug delivery system for AAP.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.205-210
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• 1992

In order to develop a controlled-release oral drug delivery system (DDS) of theophylline (TP), microporous membrane-coated tablets were prepared and evaluated in vitro and in vivo. Rapidly water-soluble core tablets of TP (300 mg) were prepared by wet granulation and compression technique, Then the core tablets were spray-coated with polyvinylchloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of coating suspensions on the pharmaceutical characteristics such as membrane strength and dissolution was investigated in vitro. The membranes remained unbroken in pH 1.2 buffer at $37^{\circ}C$ at least for 2 hours after the disintergration test. TP was released from the coated-released tablets at a zero-order rate over 8 hours. The release at pH 1.2 and 4.0 was similar in rate but a little more rapid than that at pH 6.8. The coated tablets were administered to three healthy male volunteers and their saliva profiles of TP were compared with those from the commercial sustained release TP tablets such as Slobid and Asconthin. Saliva TP concentrations from the coated tablets were successfully sustained over 48 hours after the dosing and were comparable to those of the commercial sustained-release tablets. The membrane-coating technique is very simple and does not need any sophisticated equipments. In this respect, the membrane-coated tablets may be superior to the commercial sustained-release tablets and this technique is worth adopting by the pharmaceutical industries.